Studies in the Azulene and Tropolone Series

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STUDIES I3ST THE AZULBKS AETD TBQPQLQUB 3BBIE3«

A (Thesis f o r th e d e g r ee o f P h.D .

AETDBBff B. SOMERVILLE, B . S o . , A . B . I . Q .

G lasgow U n iv e r s it y

Septem ber, 1 9 4 9 ,

ProQuest N um ber: 13870200

All rights reserved INFORMATION TO ALL USERS The q u a lity of this re p ro d u c tio n is d e p e n d e n t u p o n the q u a lity of the co p y su b m itte d . In the unlikely e v e n t that the a u th o r did not send a c o m p le te m a n u scrip t and there are missing p a g e s, these will be n o te d . Also, if m a te ria l had to be re m o v e d , a n o te will in d ic a te the d e le tio n .

uest P roQ uest 13870200 Published by ProQuest LLC(2019). C o p y rig h t of the Dissertation is held by the A uthor. All rights reserved. This work is p ro te cte d a g a in s t u n a u th o rize d co p yin g under Title 17, United States C o d e M icroform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 4 8 1 0 6 - 1346

A cknow ledgm ents. The a u t h o r w i s h e s t o t h a n k P r o f e s s o r J.W . Gook, D .S c ., Jf*.R.S. f o r h i s c o n s t a n t h e l p and i n v a r i a b l e e n c o u ra g e m e n t t h r o u g h o u t t h i s w o rk . M i c r o a n a l y s e s w e re c a r r i e d o u t b y Mr. J .M .L . Gameron and M iss R .H . Kennaway. f o r p e r m i s s i o n t o w ork i n t h e l a b o r a t o r i e s o f t h e E i d g e n S s s i s c h e f e c h n i s c h e H o c h s c h u le , Z llr ic h , fro m May t o S e p tem b er 1948, t h e a u t h o r i s i n d e b t e d t o P r o f e s s o r L . R u z ic k a ; and f o r v a l u a b l e a d v io e d u r i n g t h i s p e r i o d , t o P r o f e s s o r P .A . P l a t t n e r and D r . A. E t l r s t .

M io ro a n aly se s i n t h i s s e c t i o n

w ere c a r r i e d o u t b y H e r r W. M a n se r. E o r a M a in te n a n c e A llo w a n ce d u r i n g 19 4 5 -4 6 t h e a u t h o r i s i n d e b t e d t o t h e D e p a rtm e n t o f S c i e n t i f i c and I n d u s t r i a l R e s e a r c h , and f o r a g r a n t t o w a r d s e x p e n s e s i n Z tlr ic h t o t h e U n i v e r s i t y o f G lasgow .

0 o n t e n t s .

P art I A z u len e s*

1

E x p e r im e n ta l*

58

B ib lio g ra p h y *

71

T ro p o lo n e s*

74

Exp e r im e n t a l *

95

P art II

R eferences:

113.

P art I

-

A z u len e s.

Summary. A new s y n t h e s i s o f a z u l e n e i s d e s c r i b e d . S u b e ro n e i s c o n d e n s e d w i t h d i e t h y l s u o o i n a t e , t h e p r o d u c t (X X III) o y c l i s e d and t h e r e s u l t i n g k e t o - e s t e r h y d r o l y s e d and d e o a r b o x y l a t e d t o 1 - k e t o - o o t a h y d r o a z u l e n e (XXIV). T h is h a s b e e n r e d u c e d b y a lum in ium i s o p r o p o x i d e t o t h e c o r r e s p o n d i n g o a r b i n o l , and b y t h e Clemmensen m e th o d , a f t e r h y d r o g e n a t i o n o f t h e d o u b le b o n d , t o d e o a h y d r o a z u l e n e . T hese p r o d u c t s have b e en d e h y d ro g en ated to g iv e a zu len e i n s m a ll y i e l d s . The s y n t h e s i s o f 1 - p h e n y l a z o l e n e fro m t h e k e t o n e XXIV was a t t e m p t e d , b u t h a s n o t b e e n s u o o e s s f u l . A s i m i l a r c o n d e n s a tio n o f 2 : 3 -b en zo su b ero n e w ith d i e t h y l s u o o in a te fo llo w e d by o y c l i s a t i o n e t c . l e d to 1 - ke t oh ex ahy d rob enz az u l ene (XXXII) w h ic h h a s b e e n r e d u c e d b y v a r i o u s m ea n s, b u t d e h y d r o g e n a t i o n o f t h e r e d u c t i o n p r o d u c t s to 4 : 5 -b en z az u len e h a s n o t been a cc o m p lish e d . 2 - M e t h y l - 6- o a r b e th o x y a z u l e n e h a s b e e n p r e p a r e d b y t r e a t m e n t o f 2- m e t h y l i n d a n e w i t h d i a z o a c e t i o e s t e r and d eh y d ro g en atio n of th e p ro d u c t. T h is h a s b e e n h y d r o l y s e d t o t h e f r e e a c i d , am m onolysed t o t h e a m id e , and r e d u o e d w i t h l i t h i u m a lu m in iu m h y d r i d e t o 2- m e t h y l - 6- h y d r o x y m e t h y l a z u le n e . A t t e m p t s a t Hofmann d e g r a d a t i o n o r l i t h i u m a lu m in iu m h y d r i d e r e d u o t i o n o f t h e a m id e, i n o r d e r t o o b t a i n a m in e s , w ere u n s u c c e s s f u l .

E a r l y w o rk . The name a z u l e n e was f i r s t g i v e n t o t h e b l u e c o l o u r ­ ed) i n g m a t t e r o f oam om ile o i l , w h ich h a s b e e n u s e d a s a s o o t h i n g a g e n t f o r b u r n s and s k i n i r r i t a t i o n s f o r a v e r y lo n g tim e .

About 50 o t h e r e s s e n t i a l o i l s e i t h e r p o s s e s s

su c h c o l o u r s o r c a n g i v e r i s e t o them b y t r e a t m e n t w i t h a c i d s o r by d eh y d ro g en atio n . I n v e s t i g a t i o n o f t h e s e c o l o u r i n g m a t t e r s made l i t t l e p ro g re ss u n t i l S h e m d a ^ s d isco v ery in 1 9 1 5 ^

th a t th ey

c o u l d b e e x t r a c t e d fro m t h e e s s e n t i a l o i l s w i t h s t r o n g m i n e r a l a c id s,

su c h a s 80$ p h o s p h o r i c a c i d .

A r e d c o m p le x i s fo rm e d

w h ic h d i s s o c i a t e s o n d i l u t i o n w i t h w a t e r , and t h e c o l o u r i n g m a tte r can th e n be e x tr a c te d w ith hydro carb o n s o l v e n ts .

In

t h i s way S h e r n d a l o b t a i n e d hom ogeneous m a t e r i a l s , f o r m in g b la c k p ic r a te s .

T h e i r f o r m u l a was

in d ic a tin g r e ­

la tio n s h ip to th e se sq u ite rp e n e s . By 1936 a l a r g e num ber o f a z u l e n e s h a d b e e n i s o l a t e d i n t h i s way fro m d i f f e r e n t s o u r c e s , b u t on s y s t e m a t i c com­ p a r i s o n t h e num ber o f d i s t i n c t i n d i v i d u a l s was f o u n d t o b e o n l y f i v e - chan* , - fro m cam om ile o i l , d e h y d ro g e n a tio n o f g u a jo l,

S

-gua;}- fro m s u l p h u r

fro m s e l e n i u m d e h y d r o ­

g e n a t i o n o f g u a j o l , l a c t a r - from t h e fu n g u s l a c t a r i u s (4 ),(6) d e l i o i o s u s 1 . and v e t i v a z u l e n e fro m v e t i v e r o i l T h ese a r e known as t h e " n a t u r a l "

a z u le n e s , though in f a c t

th e y a re p ro b a b ly n o t p r e s e n t in th e p l a n t as such, b u t a re form ed d u r i n g t h e e x t r a c t i o n o f t h e e s s e n t i a l o i l . a r e a l l i s o m e r i c , h a v in g t h e f o r m u l a

They

0a r l y w ork

shov/ed t h a t t h e y c o n t a i n e d two r i n g s and f i v e d o u b le b o n d s . O x i d a t i o n g a v e f r a g m e n t s to o s m a ll t o be o f a n y u s e and i n v e s t i g a t i o n was t h e r e f o r e d i r e c t e d t o w a r d s t h e i r h y d r o ­ g e n a t i o n p r o d u c t s and t o w a r d s t h e p a r e n t s e s q u i t e r p e n e s . S tru c tu re . I n 1936 P f a n and P l a t t n e r ^ ^

e lu c id a te d th e s tr u c tu r e

o f th e a z u le n e s th ro u g h a stu d y o f th e r e l a t e d s e s q u ite r p e n e k e t o n e s e x t r a c t e d w i t h G i r a r d * s r e a g e n t fro m v e t i v e r o i l ^ 9 * ' ^ T hese k e t o n e s w e re c o n v e r t e d t o a m i x t u r e o f s e m ic a r b a z o n e s w h ic h c o u l d be s e p a r a t e d b y c r y s t a l l i s a t i o n i n t o a d - and an 1- fra c tio n ,

and t h e p u r e k e t o n e s r e g e n e r a t e d fro m t h e s e w e re

d e sig n a te d h av e th e fo rm u la

and

/3 -v e tiv o n e r e s p e c t i v e l y .

T hese k e t o n e s

and m o l e c u l a r r e f r a c t i o n m e a su re m e n t

showed t h a t t h e y a r e b i o y c l i c

and one o f t h e i r two d o u b le

bonds i s c o n ju g a te d w ith th e k e to g ro u p .

R e d u c tio n o f th e

k e t o g ro u p t o t h e o a r b i n o l , f o l l o w e d b y d e h y d r a t i o n and d e ­ h y d r o g e n a t i o n w i t h Se o r S l e d t o a m i x t u r e o f h y d r o c a r b o n s * an a z u l e n e v e t i v a z u l e n e , c 1 gs 1Q» e u d a l e n e and 1 * 5 - d i m e t h y l 7 - i s o p r o p y l n a p h t h a l e n e , t h e f o r m a t i o n o f t h e l a t t e r two compounds sho w in g t h a t t h e r i n g s a r e f u s e d o r t h o .

The -CH = CH - 00 - s y s te m o f

^ - v e t i v o n e was now

r e d u c e d t o -OHg - CH2 - GHOH-, and t h e r e s a l t i n g d i h y d r o — ( 3 - v e t i v o l when s a b j e c t e d t o o z o n i s a t i o n s p l i t o f f a m o l e c a l e o f a c e t o n e , i n d i c a t i n g t h e p r e s e n c e o f an i s o p r o p y l i d e n e g r o a p , ti> g i v e a h y d r o x y k e t o n e I , Tahich c o a i d be d e h y d r a t e d to th e a n s a t a r a t e d k e to n e I I . red aced ,

Cn

d e h y d r a t e d and d e h y d r o g e n a t e d t o an a z a l e n e

/,—cwx I CROtf I I

T h i s i n t a r n w as f a r t h e r

-

— -Cll II

z '—CH* O3

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a z a l e n e C12H12

-C o

I —CM, II

p -v e tiv o l

I f t h e r e d a c t i o n o f ( 2 - v e tiv o n e t o d i h y d r o - v e t i v o l was c a r r i e d o a t w i t h so a ia m i n a l c o h o l , t h e n t h e s a b s e q a e n t d e g ra d a tio n p r o d a c ts , in c la d in g th e a n s a t a r a t e d k e to n e I I , w ere f o a n d t o b e o p t i o a l l y a c t i v e ;

w hereas i f th e r e d a c t i o n

w ere c a r r i e d o a t o a t a l y t i o a l l y t o g i v e a s t e r e o o h e m i o a l l y p a r e d i h y d r o - P - v e t i v o l , t h e n t h e s a b s e q a e n t p r o d a c t s w ere f o a n d t o b e i n a c t i v e , y e t g a v e no m . p . d e p r e s s i o n w i t h t h e o th e r s e r ie s .

T hese i n a c t i v e com poands w ere assam ed t o b e

i n t e r n a l l y c o m p e n s a te d , fro m w h ic h i t f o l l o w s t h a t t h e s y s te m

5.

\

C -C

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C I

c

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CO

./

--

m ast b e p r e s e n t i n d i h y d r o - (2 - v e t i v o n e , t h e two r i n g s b e i n g unequal in s iz e , m etry .

t h u s g i v i n g t h e m o le c u l e a n a x i s o f sym­

S in o e d i h y d r o - p - v e t i v o n e fo rm s a d i b e n z y l i d e n e

d e r i v a t i v e i t c a n t h e r e f o r e be f o r m u l a t e d i n a o c o r d a n c e w i t h th e iso p re n e r u le as I I I ,

th e c o rre sp o n d in g s tr u c tu r e f o r

p - v e t i v o n e b e i n g IY .

t=o III

XT

T hese f o r m u la e e x p l a i n t h e f a c t s i f i t i s a ssum ed ( a^ t h a t t h e r i n g s a r e f u s e d i n a c i s p o s i t i o n , and (b ) t h a t o a t a l y t i o h y d r o g e n a t i o n o f IY d i r e o t s t h e Me on C1Q c i s t o t h e Me on 0 ^ , r e s u l t i n g i n an i n a c t i v e compound (V ), w h i l e S a/E tO S p r o d u c e s t h e o p p o s i t e r e s u l t ( Y I ) ,

H T

h

ft*

a t any r a t e i n p a r t

ru

H

Thus t h e d e r i v a t i v e s o f Y a r e i n a c t i v e , YI a c t i v e .

and t h o s e o f

D e h y d ra tio n o f th e h y d ro x y k e to n e Y II o a n ta k e

p l a c e i n two d i r e c t i o n s , g i v i n g e q u a l am ou nts o f V I I I and I X ,

6.

OH

V II

0=?

V III

w h ic h , i f t h e meso form i s u s e d ,

IX a r e o p t i c a l a n t i p o d e s so

t h a t t h e p r o d u c t i s a r a c e m a te o f two a c t i v e f o r m s , w h e r e ­ a s when t h e a sy m m e tric fo rm o f VII i s d e h y d r a t e d ,

th e p ro d u c ts

a r e b o t h a c t i v e , b u t n o t e n a n t io m o r p h o u s . On t h i s b a s i s , t h e n , t h e a z u l e n e

woul 1 '• 1 * \ t ? I \ i . 1 < ‘ . 1 \ \ C 1 * \i . -4 4 4 * 4 J 4 . 1 • - * N v4 J * i . , \ N « J i , ..j— i— 1 1 1 -1 >

14000 tso o o

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1-Methvl-azulen 1 .4 ,7 -Trimethyl-azulen Cham-azulen Guaj-azulen 1 .4 -D im e th y l-a z u le n A zu len

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4 -M eth vl-azu Ien 4. S -I)iin e th v l-a z iile u

200011

Kl;. 1. A baorptionabanden

i* i

\ / u l e n e d e r e r * te n Cl

be W ellen za h len (»• ) der Raiiden mix! den T ab ellen en tn o m m en . D ie H o h e d er • ti B a n d en en tsp rieh t 4 0 0 ° ) a b l u e c o l o u r d e v e l o p e d , and a f t e r s e v e r a l d a y s c r y s t a l s o f a z u l e n e fo rm e d .

The l a t t e r w ere i d e n t i f i e d b y means o f t h e

t r i n i t r o b e n z e n e compound, w h ic h w as t h e n decom posed by c h r o m a to g r a p h y t o g i v e p u re a z u l e n e .

At l o w e r t e m p e r a t u r e s

( 3 0 0 - 3 5 0 ° ) up t o 60$ o f t h e d e o a h y d r o a z u l e n e was r e c o v e r e d unchanged.

D e h y d r o g e n a ti o n o f dec ahy d r o a z u l e n e w i t h s u l p h u r f o l l o w e d b y d i s t i l l a t i o n o f t h e p r o d u c t gave a b l u e f r a c t i o n , b a t 7 ( $ o f t h e s t a r t i n g m a t e r i a l was r e c o v e r e d an d much t a r r y m a t t e r was f o r m e d . A tte m p ts w ere made t o d e h y d r o g e n a t e k e t o o c t a h y d r o - , k e t o d e c a h y d r o - , and d e c a h y d r o a z u l e n e s by h e a t i n g v d t h S o r Se in se ale d ta b e s .

Ho b l a e p r o d u c t s w ere i s o l a t e d .

T r e a tm e n t o f k e t o o o t a h y d r o a z u l e n e w i t h a lu m in iu m iso p ro p o x id e in b o i l i n g to lu e n e o r x y len e gave a m ix tu re o f a c r y s t a l l i n e o a r b i n o l and a l o w e r b o i l i n g h y d r o c a r b o n , p r o sum ab ly t h e o l e f i n e fo rm ed b y d e h y d r a t i o n .

B o th o f t h e s e

p ro d u c ts c o u ld be f a i r l y r e a d i l y d e h y d ro g e n a te d w ith se len iu m , b u t much r e s i n i f i c a t i o n t o o k p l a c e and t h e y i e l d o f a z u l e n e was n o t s u f f i c i e n t t o w a r r a n t f u r t h e r i n v e s t i g a t i o n . T h a t t h e (0 * 3 j 5 ) - b i c y c l o d e o a n e s k e l e t o n c a n e x i s t i n o l a - and t r a n s - fo rm s h a s b e e n shown b y HfiLckel's worl: on t h e 4 - k e t o d e o a h y d r o a z o l e n e s and t h e

c is

A

4 .5

-o c ta h y d ro a z u le n e s

tra n s

The d e c a h y d ro a z u l e n e o b t a i n e d h e r e i s p o s s i b l y t h e r e f o r e a m i x t u r e o f s u c h i s o m e r s ( b u t Cj£ a l s o P l a t t n e r , S’l l r s t and J i r a s e kv (

3 9 , ;\ .

An a t t e m p t was a l s o made t o p r e p a r e 1 - p h e n y l a z u l e n e

by G rig n ard r e a c t i o n o f k e to -o c ta h y d ro -a z u le n e w ith phenyl m agnesium b ro m id e f o l l o w e d b y d e h y d r o g e n a t i o n .

A b lu e-g re en

o o l o u r was o b t a i n e d b u t no t r i n i t r o b e n z e n e co m p lex i s o l a t e d . I t h a s s i n c e b e e n shown b y P l a t t n e r ^ ® 0 ^ , h o w e v e r, t h a t a p h e n y l g ro u p i n t h e 1 - p o s i t i o n m i g r a t e s t o t h e E - p o s i t i o n d u r i n g d e h y d r o g e n a t i o n and t h e r e s u l t i n g 2- p h e n y l - a z u l e n e d o e s n o t form an a d d i t i o n com plex w i t h t r i n i t r o b e n z e n e . The s u i t a b i l i t y f o r l a r g e s c a l e p r e p a r a t i o n s o f t h i s sy n th e sis i s d o u b tfu l.

A p a r t fro m t h e d e h y d r o g e n a t i o n s t a g e ,

w h ic h i s n e c e s s a r y t o a l l l a b o r a t o r y s y n t h e s e s so f a r d e v i s e d , th e a c e tic a n h y d rid e -zin o o h lo rid e o y c l i s a t i o n i s u n s a t i s ­ fac to ry ,

o v e r 5CjS o f t h e s t a r t i n g m a t e r i a l b e i n g o o n v e r t e d to

a m i x t u r e o f two a c i d s .

P h e se g i v e t h e same a n a l y s i s ,

and

t h e same e q u i v a l e n t ( o a 106) i s o b t a i n e d b y d i s s o l v i n g them i n e x c e s s UaOH and b a c k - t i t r a t i n g .

D ir e c t t i t r a t i o n w ith a lc o ­

h o l i c p o t a s h , h o w e v e r, shows t h a t w h i l e one i s d i b a s i c , w i t h an e q u i v a l e n t o f c a 1 0 6 , t h e o t h e r i s m o n o b a s io , w i t h an e q u iv a le n t o f oa 212.

I n a d d it i o n , th e form er r a p i d l y d e­

c o l o u r i s e s a l k a l i n e XM nO ^ w h i l e t h e l a t t e r d o e s n o t .

fh ese

f a c t s p o i n t t o t h e f o r m u la e XXIX and XXX w i t h w h ic h t h e a n a l y s e s a r e i n a g re e m e n t ( t h e p o s i t i o n o f t h e d o u b le b o n d i n XXIX b e i n g , o f c o u r s e , assum ed) .

XXIX

xxx

A ttem p ts to c y c l i s e th e m ix tu re ,

o r th e pare l a c to n e ,

b y Johnson* s m eth o d h a v e f a i l e d c o m p l e t e l y , dae no d o a b t t o th e p resen c e o f th e e x tr a c a rb o x y l group .

B o ilin g th e

m i x t u r e w i t h a c e t y l c h l o r i d e and t r e a t i n g t h e p r o d u c t ( p r e ­ su m a b ly an a n h y d r i d e ; w i t h SnCl^ b y t h e m ethod o f Gook and (6 7 ) L aw rence f a i l e d t o p ro d u c e c y c l i s a t i o n . T r e a tm e n t o f t h e m i x t u r e o f h a l f e s t e r s X X III and XXYIII w i t h a n h y d ro u s h y d r o g e n f l u o r i d e p a r t l y c o n v e r t e d i t t o a l i q u i d a n h y d r i d e o f XXIX;

t h e r e s t o f t h e m a t e r i a l was

c o n v e r t e d t o a m i x t u r e o f XXIX and XXX.

T re a tm e n t o f t h e

h a l f e s t e r s w i t h Hi1 a f t e r h y d r o g e n a t i o n a l s o f a i l e d t o produce c y c l i s a t i o n . f u r t h e r w ork b y J o h n s o n e t a l . ^ ® ^

su g g e ste d t h a t

b e t t e r y i e l d s m ig h t b e o b t a i n e d b y c o n d e n s in g e t h y l s u c c i n a t e w ith

o^~oyano s u b e r o n e , t h e s e a u t h o r s h a v i n g c a r r i e d o u t th e

c o n d e n s a t i o n on

oC - c y a n o - k e t o h y d r o p h e n a n t h r e n e s a c c o r d i n g t o

t h e schemes o KOCfUa

h y d r o l y s i s a n d Dieckmann c o n d e n s a t i o n t a k i n g p l a c e a t t h e same t i m e .

< < -c y a n o s u b e ro n e w as t h e r e f o r e p r e p a r e d from ( 6 9 ,7 0 ) h y d r o x y m e th y le n e s u b e r o n e and h y d r o x y la m in e , but t r e a t m e n t w i t h e t h y l s u c c i n a t e and p o t a s s i u m t e r t - b u t o x i d e

d id n o t p ro d ace t h e p in k c o lo a r c h a r a c t e r i s t i c o f t h e s e con­ d e n s a t i o n s and no k e t o n i c p r o d u c t s w e re i s o l a t e d .

S im ila r

t r e a t m e n t o f h y d r o x y m e t h y le n e s u b e r o n e and m e th o x y m e th y le n e sub e r o n e g a v e a p i n k c o l o a r , b a t t h e p r o d u c t s a p p e a r e d t o c o n s is t m ain ly o f th e s t a r t i n g m a t e r i a l . 2 . B e n za zu le n e s e r i e s . B enzosuberone, th e s t a r t i n g m a t e r i a l i n t h i s s e r i e s , i s o b t a i n e d i n 87$ y i e l d by t h e c y c l i s a t i o n o f p h e n y l y a l e r y l c h l o r i d e w i t h A lC lg i n a l a r g e volum e o f b o i l i n g c a r b o n d isu lp h id e

f 71

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cf

72)

*

.

About 14$ o f b e n z o su b e r o n e i s

o b t a i n e d by t r e a t i n g t h e c h l o r i d e w i t h H3P, b u t t h e f r e e a c i d i s n o t o y c l i s e d i n t h i s w ay. P h e n y l v a l e r i c a c i d h a s b e e n p r e p a r e d i n 85$ y i e l d fro m c in n a m a ld e h y d e by c o n d e n s a t i o n w i t h m a lo n io a c i d i n p r e s e n c e o f q u i n o l i n e , r e d u c t i o n o f t h e c in n a m y lid e n e ,- m a lo n io a c i d w i t h R aney 3Ji/A l a l l o y i n UaCH s o l u t i o n and d e c a r b o x y l a ­ t i o n o f th e cru d e p ro d u ct by h e a tin g i n v a c . i n th e p re se n c e o f c o p p e r p o w d e r. Pu •fU'.CH-CHO

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T h i s r e p r e s e n t s a c o n s i d e r a b l e a d v a n c e on p r e v i o u s w o rk , i n (7 3 ) w h ic h o n l y 27$ o v e r a l l y i e l d s h a v e b e e n o b t a i n e d

A n o th e r m e th o d u s e d was t o h y d r o g e n a t e c i n n a m y l i d e n e m a lo n ic a c i d i n c e l l o s o l v e s o l u t i o n o v e r p a l l a d i s e d s t r o n t i u m c a r b o n a t e and d e c a r b o x y l a t e b y b o i l i n g t h e s o l u t i o n .

The

d e c a r b o x y l a t i o n o f c i n n a m y l i d e n e m a l o n ic a c i d by h e a t i n g i n p y r i d i n e o r q u i n o l i n e was fo u n d t o b e u n s a t i s f a c t o r y owing t o t h e f o r m a t i o n o f b y - p r o d u c t s and t a r s . C o n d e n sa tio n o f b en zo su b ero n e w ith e th y l s u c c in a te b y t h e same m ethod a s b e f o r e g a v e 67$ o f c r u d e a c i d i o m a t e r i a l w h ic h was r e f l u x e d w i t h AOgO / HA / ZnClg s o l u t i o n .

28$ o f

a n e u t r a l , k e t o n i c o i l was o b t a i n e d , t h e r e m a i n d e r o f t h e m a t e r i a l g i v i n g an a c i d i c p r o d u c t .

The n e u t r a l m a t e r i a l

was s e p a r a t e d b y d i s t i l l a t i o n i n t o a s o l i d k e t o n e m .p . 5 9 -6 0

o

whose s e m io a r b a z o n e a n a l y s e d f o r t h e r e q u i r e d k e t o h y d r o b e n z a z u l e n e 22X11, an d a s m a ll amount o f a s o l i d m .p . 1 9 9 - 2 0 1 ° w h ic h g a v e a 2 : 4 - d i n i t r o p h e n y l h y d r a z o n e o n ly on l o n g s t a n d i n g . T h i s d i d n o t a n a l y s e i n a g re e m e n t w i t h e i t h e r o f t h e s t r u c t u r e s XXXVI o r X X X III. fOfcH

XXVI

XXXI

XXXII

29 .

o XXXVI

XXXIII

xxxiv

xxm i

XXXV

An a t t e m p t t o d e h y d r o g e n a t e t h e fcetone XXXII byh e a t i n g w i t h Se i n a s e a l e d t u b e g a v e no h i g h l y c o l o u r e d p ro d u c t. The a c i d s o b t a i n e d d u r i n g t h e c y c l i s a t i o n o f XXXI w e re e x t r a c t e d w i t h HaHCO„ and t h e r e s i d u e was o b s e r v e d t o o

h a v e a p h e n o l i c s m e l l , p o s s i b l y due t o t h e p r e s e n c e o f XXXVII, t h o u g h an e t h e r e a l s o l u t i o n ga v e no c o l o u r a t i o n w i t h a q . i?eC lg . The m i x t u r e o f a c i d s h a s n o t b e e n s e p a r a t e d , b u t may c o n t a i n s e v e r a l i s o m e r s , e . g . , XXXIV and XXXV a s w e l l a s l a c t o n e s a n a l o g o u s t o XXX.

XXXVIII

The k e t o n e XXXII was r e d u c e d w i t h a lu m in iu m i s o p ro p o x id e i n b o i l i n g to lu e n e and t h e p ro d u c t s e p a r a te d i n t o th re e f r a c tio n s by d i s t i l l a t i o n :

a f a i r l y m o b il e o i l ,

b . p . 9 5 ° / o . l mm., a m ore v i s c o u s o i l , b . p . 1 2 0 ° / Q . l mm. and c r y s t a l s , m .p . 1 2 3 -1 2 4 ° . first

Jfrom t h e a n a l y t i c a l r e s u l t s t h e

o f t h e s e a p p e a r s t o b e m a i n l y t h e h y d r o c a r b o n XXXVIII,

an d t h e se c o n d a m i x t u r e o f t h i s h y d r o c a r b o n w i t h t h e o a r b i n o l XXXIX.

The h y d r o c a r b o n was h e a t e d w i t h p a l l a d i u m

b l a c k u n d e r n i t r o g e n , b u t t h e m a t e r i a l t u r n e d t a r r y and g a v e no h i g h l y c o l o u r e d p r o d u c t s .

The t r i c y c l i c k e t o n e w a s a l s o

h y d r o g e n a t e d o v e r PtOg (Adams* c a t a l y s t )

a n d R aney n i c k e l .

•The f o r m e r c a t a l y s t g a v e a m i x t u r e o f s a t u r a t e d c a r b i n o l an d h y d r o c a r b o n , b u t t h e l a t t e r g a v e a more hom ogeneous p r o d u c t , a p p a r e n tly m a in ly c a r b i n o l .

T h i s w as d e h y d r o g e n a t e d w i t h

s e l e n i u m a t c a 4 0 0 ° , b u t a l t h o u g h H^Se was e v o l v e d , t h e p r o ­ d u c t w as a t a r .

P a l l a d i u m and s u l p h u r d e h y d r o g e n a t i o n s w ere

a lso t r i e d w ith o u t su c c e ss . I t may b e n o t e d t h a t Cook, McGriimis and M i t c h e l l w e re a l s o u n s u c c e s s f u l i n do h y d r o g e n a t i n g a s i m i l a r p r e c u r s o r (8 2 ) t o 5 s6 - b e n z a z u l e n e The l i m i t i n g f a c t o r i n t h e s e s y n t h e s e s t h e n , i s t h e f i n a l d e h y d ro g e n atio n o f a r e l a t i v e l y s a tu r a te d s t r u c tu r e w h ic h g i v e s y i e l d s o f c a 1^ o r l e s s .

The d i a z o a c e t i c e s t e r

m e th o d i 3 s u p e r i o r i n t h i s r e s p e c t s i n c e t h r e e d o u b l e b o n d s

a r e p r e s e n t b e f o r e d e h y d r o g e n a t i o n , b u t e v en h e r e t h e y i e l d s a r e se ld o m more t h a n 5 -1 0 $ and o f t e n muoh l e s s ,

e sp e c ia lly

i f d e c a rb o x y la tio n i s ta k in g p la c e sim u lta n e o u sly .

I f th e

m a t e r i a l to b e d e h y d ro g e n ate d i s s a t u r a t e d ,

deca-

as e .g .,

h y d ro a z u le n e , th e r e a c tio n r e q u ir e s d r a s t ic c o n d itio n s , b u t t h e u n r e a c t e d s t a r t i n g m a t e r i a l i s r e l a t i v e l y s t a b l e and o a n b e re c o v e re d : w hereas i f i t

i s u n s a tu r a te d th e re i s a con­

s i d e r a b l e l o s s fro m r e s i n i f i o a t i o n , and t h e tim e o f c o n t a c t w i t h t h e c a t a l y s t m u st be k e p t to a minimum.

T h is a p p l i e s

e s p e c i a l l y i n t h e c a s e o f a z u l e n e i t s e l f w h ic h i s n o t so s t a b l e a s i t s h i g h e r h om olo gues and i s q u i t e r e a d i l y i s o m e r i s e d t o n a p h t h a l e n e a t t e m p e r a t u r e s a r o u n d 300

n(35, 36)

I n an a t t e m p t t o overcom e t h e s e d i f f i c u l t i e s a n a p p a r a t u s was c o n s t r u c t e d f o r d e h y d r o g e n a t i o n i n t h e v a p o u r p h a s e and s u b s e q u e n t re m o v a l o f t h e p r o d u c t s fro m t h e r e a c t i o n . T h is (7 8 ) was b a s e d on a n a p p a r a t u s d e s o r i b e d b y R u z ic k a and i s i l l u s t r a t e d i n t h e a c c o m p a n y in g d ia g r a m A*

The c a t a l y s t

o a n b e h e a t e d e l e c t r i o a l l y t o any d e s i r e d t e m p e r a t u r e ,

and

t h e r a t e o f flo w o f t h e s u b s t r a t e i s d e t e r m i n e d b y t h e n itr o g e n stre a m .

The v a p o u r i s t h e n o o n d e n s e d a n d c o l l e o t e d

i n a r e s e r v o i r and o a n b e r e t u r n e d p e r i o d i c a l l y t o t h e b o i l i n g f l a s k v i a th e t a p . T h is a p p a r a t u s was u s e d f o r t h e d e h y d r o g e n a t i o n o f d e c a h y d ro a z u le n e o v e r a ICff p a lla d iu m c h a r c o a l c a t a l y s t , b u t

*1.

some o f t h e a z u l e n e fo rm ed a p p e a r e d t o decompose i n t h e b o i l i n g f l a s k , and a t h ig h te m p e r a tu re s (o a 400°) th e f o r ­ m a t i o n o f n a p h t h a l e n e was n o t e d .

The t r i c y c l i c c a r b i n o l

o b t a i n e d b y Haney n i c k e l r e d u c t i o n o f t h e k e t o n e XXXII was a l s o v a p o u r i s e d i n t h i s a p p a r a t u s a t o_a 4 3 0 ° , b u t no o o l o u r e d p r o d u c t s w ere o b t a i n e d . The a p p a r a t u s u se d t i l l r e c e n t l y b y P l a t t n e r and h i s c o l l a b o r a t o r s i n Z d ric h f o r th e d e h y d ro g e n a tio n o f d ia z o a c e tio

e s t e r a d d u c t s was a s i m p le c o l l a r f l a s k a s shown i n

d ia g ra m B .

The s u b s t r a t e i s dHopped on to t h e h e a t e d

c a t a l y s t fro m a f i n e p i p e t t e and t h e p r o d u c t a llo w e d t o c o n ­ d e n s e i n t h e o o l l a r , from w h ic h i t o a n be rem ov ed p e r i o d i c a l l y w ith a p i p e t t e ,

th e a z u le n e e x tr a o te d w ith p h o sp h o ric a c id ,

and t h e r e s i d u e r e - t r e a t e d .

T h is h a s now b e e n r e p l a c e d b y

t h e a p p a r a t u s shown i n d ia g r a m 0 , w h io h was u s e d f o r t h e p r e ­ p a r a t i o n o f E -m e th y la z u le n e -6-o a r b o x y lic e s t e r as d e s c rib e d b e lo w .

The c a t a l y s t i s c o n t a i n e d i n t h e h o r i z o n t a l p o r t i o n

o f th e tu b e ,

th e v e r t i c a l p a r t b e in g l o o s e ly packed w ith

g l a s s w ool i n o r d e r to e n s u r e t h e v a p o r i s a t i o n o f t h e m a te ria l b efo re i t reach es th e c a t a l y s t .

H e re a g a i n t h e

a z u l e n e i s e x t r a c t e d fro m t h e p r o d u c t b e f o r e r e - c y c l i n g , w h ic h may b e r e p e a t e d s e v e r a l t i m e s . B e C e n tly ( A p r i l 1949) (74 ) Uunn and B ap so n have d e s c r ib e d an a p p a ra tu s f o r vapour p h a s e d e h y d r o g e n a t i o n i n v a cu o w h ic h h a s a p p a r e n t l y b e e n

v e r y s u c c e s s f u l i n t h e p r o d u c t i o n o f 1 : 2- b e n z a z u l e n e fro m t h e c a r b i n o l X L v/hich c o u ld n o t b e d e h y d r o g e n a t e d "by o t h e r m e a n s .

oh

XL

A s t i l l more r e c e n t p a p e r (May 1949) b y t h e s e a u t h o r s ^ 8(^ d e s c r i b e s t h e d e h y d r o g e n a t i o n o f XLI t o 4 : 5 - b e n z a z u l e n e XXVII, w h ic h h o w e v e r, was f o u n d t o b e u n s t a b l e an d h a s o n l y b e e n i s o l a t e d as th e W

o r t r i n i t r o b e n z e n e co m p lex es.

A f u l l c h e m ic a l i n v e s t i g a t i o n o f t h e a z u l e n e stru c tu re s t i l l m e th o d .

a w a its th e d iso o v e ry o f a s u i t a b l e s y n th e tic

The m o st h o p e f u l l a r g e s c a l e p r o c e s s so f a r r e ­

p o rte d i s th e p o ly m e ris a tio n o f a c e ty le n e w ith a n ic k e l c y a n i d e o a t a l y s t w h ic h was d e v e l o p e d i n Germany d u r i n g t h e war f o r th e s y n t h e s i s o f c y c lo o c ta te tr m e n e produced as a by p ro d u c t i n t h i s r e a c t i o n ,

(52)

.

A z u le n e i s

and i s b e l i e v e d t o

have been o b ta in e d in f a i r l y la r g e q u a n t i t i e s , b u t s in c e i t i n v o l v e s h a n d l i n g a c e t y l e n e a t 15 atm* p r e s s u r e i t i s n o t s u ita b le f o r o rd in a ry la b o ra to ry u se.

D u r in g a few m o n th s s p e n t i n t h e l a b o r a t o r i e s o f P r o f e s s o r L* B u z io k a and P r o f e s s o r P.A* P l a t t n e r a t t h e E i d g e n d s s i s e h e T e o h n is c h e H o c h s c h u le , Z & rich , some new com­ p o u n d s o f t h e a z u l e n e s e r i e s w ere p r e p a r e d b y u t i l i s i n g t h e

c o m p a r a t i v e l y r e a d i l y a v a i l a b l e 2- m e tb .y l- 6 - o a r b e t h o x y a z u . l e n e . T h is e s t e r (XLH) was made b y t r e a t i n g 2 - m e t h y l i n d a n e w i t h d i a z o a c e t i o e s t e r and d e h y d r o g e n a t i n g t h e medium b o i l i n g f r a c t i o n o f t h e p r o d u c t w i t h 10$ p a l l a d i u m c h a r c o a l i n t h e v a p o u r p h a s e a p p a r a t u s p r e v i o u s V m e n tio n e d ( d i a g r a m G ) .

T h is

p r o c e s s g a v e o v e r a l l y i e l d s o f £ a 7$ fro m 2- m e t h y l i n d a n e .

A

s p e c im e n o f 2 - m e t h y l a z u l e n e f o r X - r a y and i n f r a - r e d m e a s u r e ­ m e n t s was a l s o p r e p a r e d b y d e h y d r o g e n a t i n g t h e a d d i t i o n p r o ­ duct a f te r h y d ro ly sis.

The y i e l d i n t h i s c a s e w as o a 2*5$

fro m 2- m e t h y l i n d a n e . I t was f i r s t o f a l l d e s i r e d t o p r e p a r e t h e amide X L I I I and a t t e m p t i t s

d e g r a d a t i o n b y t h e Hofmann r e a c t i o n t o t h e

am ine XLIV, a t y p e o f compound h i t h e r t o unknown i n t h e a z u l e n e se rie s.

The e s t e r was t h e r e f o r e h y d r o l y s e d w i t h 1$ a l c o h o l i c

p o t a s h t o t h e f r e e a c i d XLV, w h ic h was t h e n t r e a t e d w i t h t h i o n y l c h l o r i d e and ammonia.

Ho amide was o b t a i n e d h o w e v e r,

t h e p r i n c i p a l p r o d u c t b e i n g a g r e e n am orphous compound s o l u b l e o n ly in a lc o h o ls .

H ext t h e e s t e r was t r e a t e d w i t h a l c o h o l i c

ammonia i n t h e c o l d , b u t a f t e r s t a n d i n g f o r a week and t h e n r e f l o x i n g , no am ide was o b t a i n e d .

T r e a tm e n t o f t h e e s t e r

a t 1 9 0° f o r 23 h o u r s w i t h ammonia g a s i n 96$ e t h a n o l c o n t a i n ­ i n g a few d r o p s o f e t h y l e n e g l y c o l g a v e t h e am ide i n o a 76$ y ie ld ,

to g e th e r w ith a l i t t l e

o f th e f r e e a c i d .

I t is

i n t e r e s t i n g t o n o t e t h a t when 99$ a l c o h o l w as s u b s t i t u t e d ,

v ery l i t t l e

amide was fo rm e d and t h e e s t e r w as r e c o v e r e d

unchanged. The Hofmann r e a c t i o n on t h e amide X L III w as a t t e m p t e d u s i n g sodium h y p o c h l o r i t e , a s i t was t h o u g h t t h a t h y p o b r o m it e m ig h t l e a d t o h a l o g e n a t i o n o f t h e a z u l e n e n u c l e u s .

Hypo-

o h l o r i t e was f o u n d t o be w i t h o u t a c t i o n on g u a j a z u l e n e u n d e r th e c o n d itio n s o f th e r e a c t i o n .

The amide was k e p t f o r 2

h o u r s a t 35° w i t h a q u e o u s H aO HrH aO Cl, b u t was r e c o v e r e d l a r g e l y unchanged.

I t was n e x t s o u g h t t o p r e p a r e t h e

u r e t h a n e XLVI b y o a r r y i n g o u t t h e r e a c t i o n i n m e t h a n o l , b u t h y d r o l y s i s r e s u l t e d a n d much o f t h e amide was c o n v e r t e d t o th e f r e e a c id .

The r e s t o f t h e m a t e r i a l w as n o t a c i d s o l u b l e .

36.

XUi

i J k< m /(:h> h

Li AIH4

COA>Hv

fltOH

X L . Ill

Hof**™i

Nil

Owing t o s h o r t a g e o f tim e t h e Hofmann r e a c t i o n was n o t p u r s u e d , and a t t e m p t s w e re made t o r e d u c e t h e amide w i t h l i t h i u m a lu m in iu m h y d r i d e t o o b t a i n t h e am ine XLVII, b u t t h e s e w e re u n s u c c e s s f u l ,

o n ly

a

t r a c e o f p in k a c id s o lu b le m a t e r i a l

b e in g o b ta in e d . 2 - M e th y l- 6 - o a r b e th o x y a z u le n e w as lith iu m v io le t

a lu m in iu m h y d r id e a lc o h o l

X L V III.

and r e a d ily

gave

a lso

tre a te d

w ith

a c ry s ta llin e ,

A s i m i l a r v i o l e t com pound w as a ls o

p ro d u o e d b y r e d u c t i o n o f t h e f r e e a c i d 2 LY. w i t h L iA lH ^, b u t

t h i s m a t e r i a l w as n o t c h a r a c t e r i s e d .

D u r in g t h e r e d u c t i o n

o f t h e e s t e r a t r a c e o f p u r e b l u e m a t e r i a l , n o t a b s o r b e d on t h e c h ro m a to g ra m , and w i t h a oom plex s p e c tr u m s u g g e s t i n g 2 : 6 - d i m e t h y l a z u l e n e XLIX, was o b t a i n e d .

38.

E x p erim e n tal 1.

A a a le n e S e r i e s .

S a b e ro n e (, 1 )v M ethod o f M o s e t t i g and B a r g e r ( 6 6 > 480 g . o y c l o h e x an o n e d i s s o l v e d i n 600 m l . m e th a n o l was added t o 8 . 7 5 1 . o f an e t h e r e a l s o l a t i o n c o n t a i n i n g 269 g . d iaz o m e th an e .

(The l a t t e r was p r e p a r e d fro m n i t r o s o m e t h y l -

a r e a i n t h e a s a a l way and e s t i m a t e d b y t r e a t i n g a sa m p le w i t h e x c e s s g l a o i a l a c e t i o a o i d and m e a s n r i n g t h e n i t r o g e n g i v e n o ff) .

The m i x t a r e was c o o l e d i n i t i a l l y t o 0° b a t a s o n l y a

s lo w r e a c t i o n s e t i n i t w as a l l o w e d t o s t a n d a t room t e m p e r a -

I

t a r e f o r two w e e k s , a f t e r w h ic h i t becam e a lm o s t c o l o a r l e s s . The e t h e r and m e t h a n o l w e re d i s t i l l e d o f f a n d t h e r e s i d a e f r a o t i o n a t e d , d a r i n g w h ic h 15 g . o f a w h i t e , h y g r o s o o p i o s o l i d m. 1 2 8 - 3 5 ° s e p a r a t e d and was f i l t e r e d o f f (p o ly m e th y le n e s S j o f . M o s e t t i g and B a r g e r l o c . o i t . ) .

The s e p a r a t i o n was f o a n d

jj

t o be o n s a t i s f a o t o r y owing t o t h e p r e s e n c e o f o y o l o - o o t a n o n e and o t h e r b y p r o d a o t s so t h e f r a c t i o n s w e re r e - c o m b in e d and

j

t r e a t e d w i t h s o d ia m b i s a l p h i t e s o l a t i o n .

j

A f t e r w a s h in g w i t h

e t h e r t h e oompoand was s te a m d i s t i l l e d w i t h Ha^GO^, t h e

j

d istilla te

)

d r ie d and r e - d i s t i l l e d i n v a c .

b . 7 3 - 7 7 ° / 2 3 mm. ( 2 8 $ ) .

155 g . ,

I t was i d e n t i f i e d a s s a b e r o n e b y

m eans o f t h e s e m io a r b a z o n e w hich c r y s t a l l i s e s fro m a l o o h o l i n s h i n i n g p l a t e s m. 1 6 2 - 1 6 3 . 5 ° , w h i l e c y o l o h e x an o n e s e m i c a r bazone c r y s t a l l i s e s

i n e f f l o r e s c e n t n e e d l e s m. 1 6 6 - 1 6 7 . 5 °

w h ic h a r e e a s i l y d i s t i n g u i s h e d .

M ixed m . p . 1 5 6 - 1 5 9 ° .

The

r e s i d u e s fro m t h e b i s u l p h i t e e x t r a c t i o n s w e re t r e a t e d w i t h s e m i o a r b a z i d e h y d r o c h l o r i d e and p y r i d i n e i n a q . a l c o h o l and g a v e 3 .0 1 g . o f a s e m io a r b a z o n e m. 1 6 1 - 1 6 3 ° , m ixed w i t h s u b e r o n e s e m i c z . m. 1 5 1 - 1 5 4 ° , m ix ed w i t h o v o l o h e x a n o n e s e m io z . m. 1 5 0 -1 5 5 ° ( o y o l o - o o ta n o n e s e m io z . m. 1 6 3 - i 6 4 . 5 ° ) . The r e s i d u e s fro m t h i s t r e a t m e n t w e re d i s t i l l e d and g a v e 138 g. , b . 1 4 0 ° /2 3 mm. o f a y e l l o w o i l w h io h t u r n e d deep o r im s o n on s t a n d i n g , and 2 0 .2 g . , b . 1 6 0 - 1 8 0 ° / 2 3 mm. o f a t h ic k o rang e o i l .

T h ese c o r r e s p o n d w i t h t h e b y p r o d u o t s

found by K o h l e r ^ . 1 ).

A* - o v o l o h e x e n v l c a r b i n o l

2) . p i - c y o l o h e x r l d i o x a n e ( ? )

b . 9 2 - 9 4 ° / l 5 mm. b . 1 4 7 . 5 - 1 4 8 ° / l l mm. / c

e

j

( i i ) M ethod o f K o h l e r , T i s h l e r , P o t t e r and Thomson To a s t i r r e d m i x t u r e o f 10 m l . o y o l o h e x a n o n e . 10 m l . a b s . m e t h a n o l an d 50 mg. a n h y d r . Ha^CO^ was a d d e d 1 m l. n itro s o m e th y lu re th a n e .

A f te r an in d u c t i o n p e rio d o f about

30 m i n a t e s , r e a c t i o n commenced, a s e v i d e n c e d b y a r i s e i n t e m p e r a t u r e and e v o l u t i o n o f n i t r © g e n .

The t e m p e r a t u r e was

k e p t a t 2 0 - 2 5 ° b y i c e w a t e r and t h e r e m a i n d e r o f t h e 12 g .

40.

n i t r o s o m e t h y l u r e t h a n a a d d e d o v e r two h o u r s . The m i i t u r e was s t i r r e d f o r a f a r t h e r h o a r and l e f t o v e rn ig h t.

A f t e r re m o v in g t h e a l o o h o l t h e k e to n e was p u r i -

f i e d t h r o a g h t h e h i s a l p h i t e oompoand, and r e d i s t i l l e d . Y ie ld ,

5 g.

(3 -o a r t e t h o x y -

b . 1 7 8 - 1 8 2 ° / 7 6 0 mm. (4S?i) .

9 - A '-aaberenyl propionic

a o i d ZZII1.

( S to b b e

con d en sation on sab e r o n e . ) 50 g . sab e r o n e a n d 120 g . e t h y l s a o e i n a t e w e re a d d e d t o a o h i l l e d s o l a t i o n o f 2 5 g . p o t a s s i u m i n 500 m l. t - b a t y l a l o o h o l , and t h e m i x t u r e , w h ic h d e v e l o p e d a d e e p p i n k o o l o a r , was r e f l u x e d 40 m i n a t e s ,

i n a n a tm o s p h e r e o f n i t r o g e n .

o o o l i n g a n d a c i d i f y i n g w i t h HC1 ( l j 5 )

A fte r

t h e a l o o h o l w as rem oved

a n d e r r e d a o e d p r e s s u r e , t h e o i l e x t r a c t e d w i t h e t h e r , w h ic h , a f t e r w a s h in g , was e x t r a c t e d w i t h HagOO^ s o l a t i o n .

T h is was

w ash ed w i t h e t h e r and a c i d i f i e d , y i e l d i n g 98 g . G rade a c i d i c m a t e r i a l , w h ic h on d i s t i l l a t i o n g a v e t h e f o l l o w i n g f r a c t i o n s *1) b . 1 6 0 ° / l * 5 mm;

o a 10 ml*

2) b . 1 8 0 ° / l . 5 mm.

s o l i d i f i e d to sm a ll w h ite n e ed les* an o i l .

T h ese f r a c t i o n s ( i s o m e r i o ) w e re n o t s e p a r a t e d * t o t a l y i e l d 7 2 .5 g . ( 68$ ) . A s m a l l amount o f t h e s o l i d w as c o l l e c t e d and c r y s t a l l i s e d fro m p e tro le u m * m .p . 6 8 - 7 0 ° .

c l u s t e r s of w h ite n e e d le s ,

41.

(E ound:

G ■ 6 5 .1 $ , H - 8 . 2 $ ;

Gi 3 S 2 0 °4 r e q a i r e s C = 6 5 .0 $ ,

H * 8 .3 $ ). E x a m in a tio n o f th e r e s i d u e s a f t e r th e a l k a l i n e e x t r a c t i o n r e v e a l e d some u n c h an g e d sob e ro n e w h ic h on r e - t r e a t ­ m ent g a v e a f a r t h e r q u a n t i t y o f h a l f e s t e r , b r i n g i n g t h e t o t a l y i e l d ap t o 8 0 $ . 1 -k e to -

A 9 *1Q- o c t a h y d r o a z a l e n e XXIY. 1 3 .6 g . o f t h e above m i x t a r e o f i s o m e r s was d i s s o l v e d

i n 155 m l . a c e t i c a n h y d r i d e and 78 m l. g l a c i a l a c e t i c a c i d c o n t a i n i n g 20 mg. f a s e d z i n c c h l o r i d e p e r m l .

T h is w as r e -

fla x e d fo r 3 .1 /2 h o a rs in a c o rre n t o f n itro g e n .

155 m l .

w a t e r was t h e n a d d ed f o l l o w e d b y 62 m l . c o n c . HC1 and t h e s o l a t i o n r e f l a x e d a f a r t h e r 45 m i n a t e s t o h y d r o l y s e t h e i n t e r ­ m ed iate

P —k e t o e s t e r .

The s o l v e n t w as d i s t i l l e d o f f i n

v a c . and t h e r e s i d a e d i g e s t e d w i t h 200 m l . 5$ KGK f o r l / 2 h o a r on t h e s te a m b a t h .

Erom t h i s b y e t h e r e x t r a c t i o n w as

o b t a i n e d 2 . 1 g . k e t o n e , b . 6 2 - 6 4 ° / 0 . 1 mm. ( 2 5 $ ) .

A fte r 0

p a r i f i c a t i o n t h r o a g h t h e s e m io a r b a z o n e (m. 2 3 5-236 d e c o m p .; Found C = 6 3 .8 $ ; C = 6 3 .8 $ ;

H = 8 .1 $ ;

H = 8 .2 $ ;

c o lo u rle s s o il,

H = 2 0 .3 $ ).

b . 5 8 - 6 0 ° / 0 * l mm.

(Found 0 = 7 9 .9 $ ; H 3 9 .3 $ ).

1 = 2 0 .4 $ ;

H = 9 .2 $ ;

^ 11^ 1 7 ^®$ r e q a i r e s

T h is w a s o b t a i n e d a s a ]ipS = 1 . 5 2 7 5 .

G10S1 4 0 r e q a i r e s 0 = 8 0 .0 $ ;

D a r in g t h e o y o l i s a t i o n c o n s i d e r a b l e d a r k e n i n g o c c u r r e d e v e n when ,TA n a l a r ,T r e a g e n t s w ere u s e d .

The a l k a l i n e

e x t r a c t s on a c i d i f i c a t i o n ga v e 1 .5 2 g . o f a b r o w n is h w h i t e s o l i d m. 1 5 7 - 1 6 0 ° . On a l a r g e r s c a l e 5 7 .5 g . m a t e r i a l was t r e a t e d as above:

a deep p u r p l e c o l o a r d e v e l o p e d on a d d in g t h e HOI, and

some s o l i d p r e c i p i t a t e d d a r i n g t h e re m o v a l o f t h e s o l v e n t . 8 . 5 g . k e t o n e (2 4 $ ) was o b t a i n e d and a t o t a l o f 2 8 .2 g . a c i d i c s o l i d , i n c l u d i n g two l o t s o f m a t e r i a l p r e c i p i t a t e d a s a b o v e , and a t h i r d o b t a i n e d b y a l k a l i e x t r a c t i o n .

T hese

h a d m .p . 1 6 8 -1 7 0 ° , 1 8 4 - 1 8 6 ° and 1 7 4 - 1 7 5 ° ( s i n t . 1 5 7 ° ) r e s p e c t i v e l y a n d on p u r i f i c a t i o n b y r e p e a t e d c r y s t a l l i s a t i o n fro m d i l a t e a c e t i c a c i d w ere f o u n d t o c o n t a i n two p u r e com­ pounds o n ly : Q = 6 2 .3 $ ; (F o u n d :

(A) s t r o n g w h i t e n e e d l e s m. 1 7 1 ° (F o u n d : H = 7 .2 $ ) a n d (B) s m a l l w h i t e p l a t e s m. 1 8 4 - 1 8 6 °

0 = 6 2 .3 $ ;

H 3 7 .4 $ ).

M ixed m .p . 1 5 8 - 1 6 1 ° .

The

f o r m e r d e c o l o u r i s e d KMh04 r a p i d l y , t h e l a t t e r d i d n o t . T it r a t i o n of a c id by p ro d u c ts. 71 mg. A was d i s s o l v e d i n 10 m l. 0 . 1 H HaGH and t i t r a t e d w ith

0 . 1 1 HOI u s i n g p h e n o l p h t h a l e i n a s i n d i c a t o r . T itra tio n

=

.* .

71 mg. A

=

i.e .

e q u iv . o f A 3

2 .4 m l. 7 .6 m l. 0 . 1 I HaCH ^ x 1 0 ,0 0 0 1000 7 .6

B

B was t i t r a t e d s i m i l a r l y : i.e .

7 7 .5 mg. = 8 . 0 m l . 0 . 1 U HaOH

e q u iv . of B = 97.

D i r e c t t i t r a t i o n s w e re t h e n c a r r i e d o u t i n a l c o h o l i c s o l u t i o n u s i n g a l c o h o l i c KGK w i t h p h e n o l p h t h a l e i n a s i n d i c a t o r . 10 m l . 81 mg.

0 .1 U HOI - 1 2 .1 m l . KQH A

*

.* . e q u iv . of

9 . 2 m l . KOH Ar

^ x 1 2 .1 x 1000 = 1000 9.2 ~

1 0 6 .5 -------------------------

75 mg. B = 5 .1 m l . XQH . *. e q u i v . o f B (XXIX ( g11h 1 6 g4 ) r e q u i r e s XXX

^Gh Hi 6 ^4 ^

=—^ x 1 2 .1 1000

x 1000 = 5 .1

C = 6 2 .3 $ ;

H = 7 .6 $ ;

e q u iv .

= 1 06:

0 B 6 2 .3 $ ;

H = 7 .6 $ ;

e q u iv .

* 2 1 2 .)

S u b s e q u e n t p r e p a r a t i o n s o f t h e k e t o n e w e re c a r r i e d out w ith o u t p u r if y in g th e in te rm e d ia te h a l f e s t e r ,

and y i e l d s

up t o 33$ fro m s u b e r o n e w e re o b t a i n e d . 1 -Ke t o - d e c a h y d r o a z u l e n e . 1 . 3 4 g . XXIY was s h a k e n w i t h h y d r o g e n i n p r e s e n c e o f Adams* p l a t i n u m c a t a l y s t i n e t h a n o l f o r 5 h o u r s a f t e r w h ic h t h e a b s o r p t i o n was v i r t u a l l y c o m p l e t e .

The p r o d u c t gave a

s e m io a r b a z o n e m. 2 2 9 -2 3 0 ° decom p. (Found C = 6 3 .3 $ ; H = 2 0 .0 $ :

r e q u i r e s 0 a 6 3 .2 $ ;

H = 8 .9 $ ;

H = 9 . 1 $ ; I = 2 0 .1 $ )

U s in g Pd/SrGOg t h e r e d u c t i o n w as c o m p le te i n 2 . 1 / 4 h o u r s , t h e same p r o d u c t b e i n g fo rm e d .

D e c a h y d ro a z u le n e . 0 .9 5 g . 1 - k e t o - d e c a h y d r o a z u l e n e was r e d u c e d b y Qlemm ensen*s m eth o d u s i n g 2 g . am alg am ated z i n c an d 6 m l . HOI (7 p a r t s cone . HOI: g la c ia l a c e tic a c id .

3 p a r t s H^O) w i t h a few d r o p s o f A f t e r 12 h o u rs * r e f l u x i n g 25$ o f t h e

m a t e r i a l was u n c h a n g e d .

A f t e r 30 h o u rs* r e f l u x i n g a 60$

y i e l d o f d e c a h y d r o a z u l e n e fc. 1 9 2 ° was o b t a i n e d , 10$ o f t h e k e t o n e b e in g r e c o v e r e d . D e h y d r o g e n a ti o n o f dec a h y d ro az u l e n e . 1 .1 6 g . dec a h y d ro a z u l e n e was r e f l u x e d w i t h 3 . 5 g . Se a t 360° f o r 4 d a y s u s i n g a l o n g n e c k e d f l a s k w i t h i n t e r n a l c o n d e n s e r , t h e t e m p e r a t u r e b e i n g a ll o w e d t o r i s e f i n a l l y to p > 4 0 0 °.

B l u e c r y s t a l s fo r m e d on t h e c o n d e n s e r and on e x ­

t r a c t i n g w i t h p e t r o l e u m a d e e p b l u e s o l u t i o n was o b t a i n e d . T h i s w as e x t r a c t e d w i t h p h o s p h o r i c a c i d ( s . g . 1 . 7 5 ) , t h e e x t r a c t w a sh e d w i t h p e t r o l e u m , d i l u t e d and e x t r a c t e d w i t h e th e r.

On e v a p o r a t i o n o f t h e l a t t e r a b l u e s o l i d r e m a i n e d .

T h i s w as t a k e n up i n 5 m l. a l c o h o l a n d warmed w i t h 1 0 0 mg. j3- t r i n i t r o b e n z e n e .

On c o o l i n g f i n e brow n n e e d l e s w e re

d e p o s i t e d w h ic h on r e c r y s t a l l i s a t i o n from a l o o h o l g a v e 56 mg. a z u l e n e t r i n i t r o b e n z o l a t e m. 1 6 5 -1 6 7 ° ( l i t . 1 6 6 . 5 - 1 6 7 . 5 ° ) • T h i s was d i s s o l v e d i n 10 m l . c y c l o h e x a n e /b e n z e n e ( 1 : 1 ) p a s s e d t h r o u g h a 5 cm. colum n o f a lu m i n a .

and

The a z u l e n e was

w a sh e d t h r o u g h w i t h 20 m l. c v o l o h e x a n e and t h e r e s u l t i n g deep

■blue s o l u t i o n d i s t i l l e d ( t h r o u g h a s h o r t colum n t o p r e v e n t v o l a t i l i s a t i o n of a zu len e ) .

B r ig h t b lu e c r y s t a l s o f a zu len e

re m a in e d m. 8 5 - 8 9 ° (m ic r o a p p a r a t u s ) ( l i t . 9 8 - 9 9 ° ) . 1 g . h y d r o c a r b o n and 0 . 2 g . s u l p h u r (1 6 $ o f t h e o r y ) w ere h e a t e d i n a l o n g n e c k e d f l a s k t o 210° when r e a c t i o n s e t i n and H^S was e v o l v e d . e v o lu tio n of

A f t e r 12 h o u r s a t 2 1 0 -2 4 0 ° t h e

a p p e a r e d t o h a v e s t o p p e d and t h e d a r k , brown

t a r r y p r o d u c t was d i s t i l l e d .

0 .7 1 g . h y d r o c a r b o n w as r e ­

c o v e r e d , f o l l o w e d b y a d ro p o f a b r i g h t dob a l t b l u e l i q u i d . The c o l o u r c o u l d b e e x t r a c t e d w i t h c o n c . p h o s p h o r i c a c i d and re g e n e ra te d by d ilu tio n w ith w a te r. H e a t i n g w i t h s e l e n i u m a t 3 60° f o r 55 h o u r s g a v e a d e e p e r b l u e p r o d u c t w i t h no t a r i y m a t t e r , b a t 63$ o f t h e h y d r o c a r b o n was r e c o v e r e d an d t h e amount o f a z u l e n e p r e s e n t was t o o s m a l l t o i d e n t i f y .

T r e a tm e n t w i t h a few mg. a - t r i o n i t r o b e n z e n e i n a l c o h o l g a v e some b l a c k n e e d l e s m. o a 110 decom p. H e a t i n g d e c a h y d r o a z u l e n e o r XXIY w i t h s e l e n i u m i n s e a l e d t u b e s a t 3 0 0 - 3 5 0 ° f o r p e r i o d s up t o 52 h o u r s g a v e no

b lu e p ro d u cts. P o n n d o r f r e d a c t i o n o f k e t o o c t a h y d r o a z a l e n e XXIY. The k e t o n e XXIY ( 2 . 7 5 g . ) was r e f l u x e d f o r 4 h o u r s w i t h a lu m in iu m i s o p r o p o x i d e ( r e - d i s t i l l e d , (5 0 m l . ) .

8 g .) in x y len e

A f t e r w a s h in g w i t h d i l . HC1 and e v a p o r a t i n g t h e

s o l v e n t , t h e p r o d u c t was d i s t i l l e d , g i v i n g two f r a c t i o n s : ( l ) m o b il e b . 8 0 ° / l 7 mm. ( 0 . 3 7 g . ) 1 4 0 ° / l mm. ( 1 . 8 2 g . ) .

and (2 ) v i s c o u s b . c_a

The l a t t e r was r e - d i s t i l l e d b . 1 4 8 ° /

1 mm., and was r e c r y s t a l l i s e d from a q . a l c o h o l t o g i v e f i n e w h ite n e e d le s m .p . 4 1 ~ 4 3 °. s a tis fa c to ry . 0

(P o u n d :

The a n a l y s i s o f t h e s e was n o t

C » 8 1 . 6 9 , 8 1 .8 2 $ ;

H = 9 .0 7 , 9 .2 6 $ :

H 0 r e q . C = 7 8 . 9 0 ; H* 1 0 . 6 0 $ ) . 10 16 The u s e of b e n z e n e o r t o l u e n e a s s o l v e n t s i n a n

a t t e m p t to p r e v e n t d e h y d r a t i o n o f t h e c a r b i n o l lo w e r e d t h e y i e l d c o n s i d e r a b l y , much k e t o n e b e i n g r e c o v e r e d . The c a r b i n o l ( 0 . 3 7 g . ) was t r e a t e d w i t h 3 : 5 - d i n i t r o b e n zo y l c h lo r id e ( 1 .5 g .) i n benzene w ith th e a d d itio n of a few d r o p s o f p y r i d i n e . c o o lin g ,

A f t e r b o i l i n g f o r a few m i n u t e s and

e t h e r was a d d e d ,

t h e p r e c i p i t a t e f i l t e r e d , w ashed

w i t h d i l u t e a c i d , a l k a l i and w a t e r .

T h i s m a t e r i a l ( m .p . c a

1 9 6 ° ) d i d n o t c r y s t a l l i s e w e l l and was t h e r e f o r e t r e a t e d w i t h < * -n a p h th y la m in e i n e t h e r .

A r e d com plex was fo rm e d w h ic h

c r y s t a l l i s e d i n s m a ll r e d n e e d l e s from m e t h a n o l , m .p . 1 9 7 - 1 9 8 ° . The a n a l y s i s o f t h i s c o u l d n o t b e i n t e r p r e t e d . C = 5 7 .6 7 $ ;

H = 3 .7 3 $ ;

(P o u n d ;

H * 1 2 .0 5 $ ).

B o th P o n n d o r f p r o d u c t s w ere d e h y d r o g e n a t e d w i t h Se a t 2 5 0 -3 3 0 ° ( 3 - 4 h o u r s )

an d w i t h p a l l a d i u m c h a r c o a l a t c a 250-

340° ( 4 5 m i n u t e s u n d e r E g ) .

Deep b l u e d i s t i l l a t e s w e re

o b t a i n e d i n a l l c a s e s fro m w hich t h e a z u l e n e c o u l d b e e x t r a c t e d

w i t h p h o s p h o r i c a c i d and c o n v e r t e d to t h e t r i n i t r o b e n z e n e c o m p le x , b u t t h e y i e l d s w ere s m a l l and much t a r was f o r m e d . D e h y d r o g e n a ti o n o f d e c a h y d r o a z u le n e i n t h e v a p o u r p h a s e a p p a r a t u s ( d i a g r a m A) u s i n g 10$ p a l l a d i u m c h a r c o a l a t c a 4 3 0 ° g a v e s m a ll am ounts o f a z u l e n e t o g e t h e r w i t h some n a p h ­ th a le n e

( i d e n t i f i e d a s t h e p i c r a t e , m .p . and m ix e d m . p . ) .

G r i g n a r d r e a c t i o n on k e t o - o c t a h y d r o a z u l e n e . P h e n y l m agnesium b r o m id e (5 0 $ e x c e s s ) was p r e p a r e d fro m 3 .9 3 g . b ro m o b e n z e n e and 0 .6 1 g . m agnesium w i t h t h e a i d of a l i t t l e d ro p w ise,

m e t h y l m agnesium i o d i d e .

To t h i s was a d d ed ,

2 .5 g . k e t o - o c t a h y d r o a z u l e n e i n d r y e t h e r .

A

y e l l o w gummy s o l i d p r e c i p i t a t e d and a f t e r s t a n d i n g o v e r n i g h t t h e m i x t u r e was r e f l u x e d 30 m i n u t e s an d t h e c o m p lex decom posed w ith ic e

and d i l . HgSO^.

The p r o d u c t , o b t a i n e d b y e t h e r

e x t r a c t i o n , c o n s i s t e d o f 3 .2 9 g . t h i c k g r e e n i s h b row n o i l , w h ic h d i d n o t d i s t i l a t w a t e r b a t h t e m p e r a t u r e u n d e r 18 mm. p ressu re. T h is was h e a t e d u n d e r r e f l u x w i t h 3 . 3 g . s e l e n i u m a t 360 ° f o r 16 h o u r s .

Some low b o i l i n g m a t e r i a l ( o a . 2 0 0 °)

a p p e a r e d t o b e p r e s e n t and a l s o some m o i s t u r e (fr o m d e h y d r a ­ t i o n o f t h e c a r b i n o l ?) b u t t h e m a in b o d y o f t h e l i q u i d s t a r t e d t o b o i l a t £ a 3 1 0 ° and H^Se was e v o l v e d so on a f t e r . On d i s t i l l i n g

t h e p r o d u c t , some y e l l o w o i l d i s t i l l e d a t c a

1 4 0 ° / l 8 mm., t h e n a d ro p o f b l u e l i q u i d a p p e a r e d a t £ a 2 20 °

( a i r b a th te m p era tu re )

f o l l o w e d b y some t h i c k g r e e n l i q u i d .

E x t r a c t i o n o f t h e c o l o u r i n g m a t t e r s w i t h c o n e . H^PO^ g a v e 72 mg. g r e e n o i l fro m w h ic h , h o w e v e r, no t r i n i t r o b e n z e n e compound c o u l d be o b t a i n e d . A tte m p te d c y c l i s a t i o n o f X X III w i t h h y d r o g e n f l u o r i d e . 5 g . c r u d e p r o d u c t from t h e S to b b e c o n d e n s a t i o n on s u b e r o n e was p l a c e d i n a p l a t i n u m c r u c i b l e w h ic h was t h e n f i l l e d w i t h 10 m l. a n h y d ro u s h y d r o g e n f l u o r i d e and l e f t f o r 5 hours*

The h y d r o g e n f l u o r i d e was t h e n a llo w e d t o e v a p o r ­

a t e , t h e r e s i d u e t a k e n up i n e t h e r a n d w ashed w i t h w a t e r and w i t h HagOOg s o l u t i o n .

The a l k a l i n e e x t r a c t y ie ld e d J .1 9 g .

o f an a c i d s i n t . 1 6 0 ° m. 1 6 6 -1 6 7 ° w hich p r o v e d t o be a m i x t u r e o f XXIX and XXX, w h i l e e v a p o r a t i o n o f t h e e t h e r l a y e r g a v e 2 .6 2 g . r e d d i s h brow n o i l b . 1 5 8 - 1 6 6 ° / 0 . 8 mm. was r e a d i l y h y d r o l y s e d b y a c i d o r a l k a l i , f o r some t i m e t o t h e a c i d d e s c r i b e d a b o v e .

The l a t t e r

or by s ta n d in g T h i s a c i d was

i d e n t i c a l w i t h XXIX - m ix ed m .p . 1 7 1 ° . H y d ro g e n atio n o f X X III. 10 g . c r u d e S to b b e c o n d e n s a t i o n p r o d u c t was h y d r o ­ g e n a t e d o v e r Pd/S rO O g.

H y d ro g en w as r a p i d l y a b s o r b e d t o

g i v e a c o l o u r l e s s o i l w h ic h was u s e d w i t h o u t f u r t h e r p u r i f i ­ c a tio n . 2 g . o f t h i s m a t e r i a l was t r e a t e d w i t h h y d r o g e n f l u o r i d e a s a b o v e , and a n o t h e r p o rtio n w jth H A /A c o /Z n C l . . 2 2

The p r o d u c t s h a v e n o t b e e n f u l l y c h a r a c t e r i s e d , b u t no k e t o n i c m a te r ia l h a s been i s o l a t e d . A tte m p te d c y o l i s a t i o n o f t h e m i x t u r e o f XXIX and

1). With

xxt.

S n C lA*

1 g . o f t h e c r u d e m i x t u r e o f a c i d s was r e f l u x e d 30 m i n u t e s i n 5 m l. a c e t y l c h l o r i d e .

A f t e r re m o v a l o f t h e

e x c e s s a c e t y l c h l o r i d e i n v a c . a t h i c k brown o i l re m a in e d w h ich p a r t l y s o l i d i f i e d .

T h is was t r e a t e d w i t h 1 . 2 5 g .

s t a n n i c c h l o r i d e i n c a r b o n d i s u l p h i d e b y t h e m ethod o f Oook and L a w r e n c e ^ .

A f t e r d e co m p o sin g t h e co m p lex w i t h i c e

and e x t r a c t i n g w i t h c a r b o n d i s u l p h i d e ,

e v a p o ra tio n o f th e

e x t r a c t g av e 0 .3 3 g . o f an o i l w h ic h c r y s t a l l i s e d a f t e r s e v e r a l m o n th s , g i v i n g l o n g n e e d l e s m. 7 1 ^ 2 ° , w h ic h h a d no k e to n ic p r o p e r tie s .

(F o u n d :

C, 6 4 .5 0 , H, 7 . 9 6 $ ) .

2J • W ith HA/ACqO/Zn O lp . 1 . 1 7 g . a c i d was r e f l u x e d 4 ^ h o u r s u n d e r n i t r o g e n w i t h 19 m l. ACgO, 6 m l. g l a c i a l . (2 0 m g ./ ml) .

HA a n d 6 m l . HA/ZnClg

0 .9 7 g . a c i d was r e c o v e r e d u n c h a n g e d .

T h is was r e p e a t e d u s i n g t h e p u r e l a c t o n e XXX w i t h sim ila r r e s u l t . H y d ro x y m e th y le n e s u b e r o n e ( W a lla c h , S t e i n d o r f f

(7 6 )

).

( i ) . HaOMe m e th o d . 2 . 1 g . 35a was d i s s o l v e d i n 30 m l. m e t h a n o l and t h e s o l u t i o n e v a p o ra te d under red u ced p r e s s u r e .

The 35aOMe was

po w d ered and 6 . 6 5 g . e t h y l f o r m a t e i n 45 m l . so d iu m d r i e d

b e n z e n e a d d e d , f o l l o w e d b y 5 g . s u b e ro n e i n 50 m l . d r y b e n z e n e , w i t h c o o l i n g and s w i r l i n g .

The f l a s k was t h e n e v a c u a t e d ,

f i l l e d w i t h Hg and l e f t o v e r n i g h t .

A f te r h y d r o l y s i s w ith

c o l d w a t e r , t h e o r g a n i c l a y e r was s e p a r a t e d and w ashed w i t h d i l u t e HaOH and t h e c o m b in ed a q u eo u s l a y e r s a c i d i f i e d . p r e c i p i t a t e d o i l was e x t r a c t e d w i t h e t h e r , tille d .

Y ie ld , 4 .8 5 g .

The

d r i e d and d i s -

b . 9 0 - 9 4 ° / l 8 mm.

( 7 8 f t) .

( i i ) . A to m ised Ha m e th o d . 2 g . Ha was a to m is e d i n b o i l i n g t o l u e n e , t h e t o l u e n e d e o a n t e d and t h e Ha c o v e r e d w i t h d r y e t h e r . f o r m a t e i n e t h e r was t h e n a d d e d , b y 4 .7 1 g . s u b e r o n e i n e t h e r .

6 .5 g . e th y l

followed w i t h c o o l i n g i n i c e , B e a c tio n s e t in a t once,

as

e v id e n c e d b y e f f e r v e s c e n c e and t h e f o r m a t i o n o f a sa lm o n p in k p r e c i p i t a t e .

A f te r s ta n d in g 2 h o u rs i n ic e w a te r, th e

m i x t u r e was a llo w e d t o s t a n d o v e r n i g h t a t room t e m p e r a t u r e and was t h e n h y d r o l y s e d w i t h m o i s t e t h e r and w orked up a s b efo re.

Y i e l d , 5 .0 1 g . (8 9 £ ) o o l o a r l e s s o i l .

b . 1 0 4-110°/

23 mm. ( l i t . b . 1 0 0 ° / l 0 mm.) c*v-cyano s u b e r o n e .

( Z ie g le r e t a l.

( 77)

).

4 . 3 2 g . h y d r o x y m e th y le n e s u b e r o n e w as s t i r r e d w i t h 4 . 3 g . p ow d ered h y d r o x y l a m in e h y d r o c h l o r i d e (IOQJg e x c e s s ) i n 50 m l . g l a c i a l a c e t i c

a c i d a t 7 0 -8 0 ° f o r 8 h o u r s .

On

c o o l i n g t h i s was f i l t e r e d from e x c e s s HHg.QH.H01 and t h e

51.

s o l v e n t rem oved i n v a c .

The o r a n g e r e s i d u e was w a sh e d w i t h

w a t e r and e x t r a c t e d w i t h e t h e r , t h e e x t r a c t b e i n g w ash ed w i t h UaHCOg s o l u t i o n t o rem ove u n c h a n g e d s t a r t i n g m a t e r i a l *

The

m ix tu re of iso m e ric is o x a z o le s o b ta in e d by e v a p o ra tio n o f t h i s e x t r a c t was d i s s o l v e d i n 50 m l.

d r y e t h e r and 10

a c o n c e n t r a t e d s o l u t i o n o f so d iu m i n

m eth an o l added.

m l. o f ' A

w h i t e p r e c i p i t a t e fo rm e d and a f t e r 1 h o u r t h i s was h y d r o l y s e d w i t h c o l d w a t e r , t h e e t h e r s e p a r a t e d and t h e a q u e o u s l a y e r s a t u r a t e d w i t h s a l t and a c i d i f i e d .

The p r e c i p i t a t e d

was e x t r a c t e d w i t h e t h e r , d r i e d and d i s t i l l e d .

o il

Y ie ld ,

1 . 6 5 g . (3 9 i l ) p a l e y e l l o w o i l , 5 . 1 4 0 - 1 4 2 ° / l 7 mm. ( l i t . 1 4 l ° / l 2 m m .)•

1 40-

T h is g r a d u a l l y d e p o s i t e d a s o l i d p o ly m e r on

s ta n d in g . The s t a b l e

saberpnyl iso x a z o le

was r e c o v e r s a xroai

x a y e r uy *•reai/menu

w ith a s a t u r a t e d a lc o h o lic s o l u t io n o f m e rc u ric c h lo r i d e , when t h e w h i t e c r y s t a l l i n e d o u b le s a l t p r e c i p i t a t e d 98-100°) .

(m. c a

I t was decom posed b y d i s s o l v i n g i n HC1, p r e -

c i p i t a t i n g t h e Hg w i t h HaOH and rem o v in g t h e i s o x a z o l e b y s te a m d i s t i l l a t i o n . o o lo u r & e s s l i q u i d

The compound was t h u s o b t a i n e d as a b . 5 0 - 5 2 ° / 0 . 2 mm.

H = 7 .6 $ ;

3J = 1 0 . 0 $ :

H = 8 *0$;

H = 1 0 .2 $ ).

(b o u n d s

0 - 6 9 .5 $ ;

CqH-^OU r e q u i r e s C = 7 0 .1 $ ;

C o n d e n s a ti o n o f 1*71 g . (5 0 $ e x c e s s )

g ^ -c y a n o s u b e r o n e and e t h y l s u c c i n a t e . flC-cyano s u b e r o n e was m ix e d w i t h 3 . 3 g .

e t h y l s u c c i n a t e a n d added t o a c h i l l e d s o l u t i o n

o f 0 .5 5 g . p o t a s s i u m i n 10 m l . t_ -b u ty l a l c o h o l .

A w h ite

p r e c i p i t a t e fo rm e d and t h e m a t e r i a l w as r e f l u x e d u n d e r Hg f o r 1 hour.

A f t e r w o r k in g up i n t h e u s u a l way some gummy

m a t e r i a l was o b t a i n e d fro m w h ic h some s t a r t i n g m a t e r i a l was re c o v e re d by a l k a l i e x tr a c t i o n .

Ho k e t o n i c p r o d u c t s w ere

iso la te d . C o n d e n s a t i o n o f h y d r o x y m e t h y le n e - s u b e r o n e and e t h y l s u o c i n a t e . 0 . 5 g . h y d r o x y m e t h y l e n e - s u b e r o n e was t r e a t e d as above w i t h 1 g . e t h y l s u c c i n a t e and 0*3 g . p o t a s s i u m i n 10 m l . t- b u ty l a lc o h o l.

A deep r e d c o l o u r d e v e l o p e d , b u t t h e p r o ­

d u c t s a p p a r e n t l y c o n s i s t e d m a i n l y o f s t a r t i n g m a t e r i a l s and p o ly m e rs.

The u se o f m e th o x y m e th y le n e - s u b e r o n e ( b . 1 1 6-

1 2 0 ° / l 3 mm., fro m h y d r o x y m e t h y l e n e - s u b e r o n e w i t h d ia z o m e th a n e i n p re s e n c e o f m eth an o l) gave s i m i l a r r e s u l t s . 2 . B en zazu len e s e r i e s . S -P h e n y lv a le ric a c id . C in nam ic a ld e h y d e (1 0 0 g . ) , m a l o n i c a c i d (8 0 g . )

and

q u i n o l i n e (98 g . ) were m ix e d and w arn ed t o a c l e a r s o l u t i o n on t h e w a t e r b a t h .

A few d r o p s o f p i p e r i d i n e w e re t h e n

a d d e d an d t h e m i x t u r e a l l o w e d t o s t a n d 4 d a y s i n t h e c o l d .

I t was t h e n warmed 2 h o u r s on t h e w a t e r h a t h , UaOH (2 7 0 g . i n 2 1 . w a t e r ) w ith e th e r .

d isso lv e d in

and t h e q u i n o l i n e e x t r a c t e d

A fte r d i s t i l l i n g o ff th e d isso lv e d e th e r,

t h e s o l u t i o n was r a i s e d t o b o i l i n g p o i n t and R aney U i / A l a l l o y (1 6 0 g . )

ad d ed w i t h v i g o r o u s s t i r r i n g

d u rin g £ h o u r

( s e o . o c t y l a lc o h o l u sed to re d u c e f r o t h i n g ) . was t h e n s t i r r e d

The m i x t u r e

a t 90° f o r -g- h o u r and f i l t e r e d .

The h o t

f i l t r a t e was now s ip h o n e d s l o w l y i n t o h o t s u l p h u r i c a c i d (6 0 0 m l . c o n e . - 1 1 .

w a ter) w ith v ig o ro u s s t i r r i n g .

On

c o o l i n g , t h e p r e c i p i t a t e d o i l was s e p a r a t e d , d i s s o l v e d i n e t h e r and w ashed f r e e fro m a lu m in iu m s a l t s .

A fte r ev ap o ra­

t i o n o f t h e e t h e r i t was t h e n h e a t e d u n d e r v a c . [oa. 2 0 mm.) i n p r e s e n c e o f c o p p e r p o w d e r, f o r 2 h o u r s a t 1 4 0 - 1 8 0 ° .

The

m e s u l t i n g p h e n y l v a l e r i c a c i d was c r y s t a l l i s e d fro m p e t r o l e u m ( 4 0 - 6 0 ° ) , m .p . 5 9 - 6 0 ° .

Y i e l d , 115 g .

(85$ o v e r a l l ) .

I n o t h e r p r e p a r a t i o n s t h e i n t e r m e d i a t e o i n n a m y l id e n e m a l o n i c a c i d was i s o l a t e d a n d h y d r o g e n a t e d i n c e l l o s o l v e s o l u t io n over p a lla d is e d stro n tiu m c a rb o n a te .

The p r o d u c t

c o u l d t h e n be d e c a r b o x y l a t e d b y b o i l i n g t h e s o l u t i o n f o r 1 h o u r.

G in n a m y lid e n e m a lo n ic a c i d was a l s o d e c a r b o x y l a t e d

d i r e c t l y b y r e f l u x i n g i n p y r i d i n e o r q u i n o l i n e , b u t much t a r was fo rm ed and t h e p r o d u c t was c o n t a m i n a t e d w i t h an u n i d e n t i ­ f i e d b y p r o d u c t , m .p . 1 3 7 - 1 3 9 ° ( l o n g w h i t e n e e d l e s from benzene or g l a c i a l a c e tic a c id ) .

2 : 3 - B e n z o s u b e r o n e - ( 1 ) XXVI

(P la ttn e r

1 9 .6 g . p h e n y l v a l e r i c

(

71)

).

a c i d was t r e a t e d w i t h 20 m l.

t h i o n y l c h l o r i d e , warmed on t h e w a t e r h a t h t i l l

e v o lu tio n

o f HOI commenced a n d t h e r e a c t i o n a llo w e d t o p r o c e e d w i t h o u t h e a t.

When e v o l u t i o n o f HOI c e a s e d t h e m i x t u r e was warmed

10 m i n u t e s on t h e b o i l i n g w a t e r b a t h and t h e e x c e s s t h i o n y l c h l o r i d e rem o ved i n vac .

The

c h l o r i d e was d i s s o l v e d i n 1 1 .

r e m a in i n g p a l e y e ll o w CSg ( d r i e d o v e r and r e - d i s ­

t i l l e d fro m a lu m in iu m t r i c h l o r i d e )

and d r i p p e d i n t o 500 m l.

c a r b o n d i s u l p h i d e and 28 g . a lu m in iu m t r i c h l o r i d e a t sim m e r­ in g p o i n t , w ith v ig o ro u s s t i r r i n g .

The a d d i t i o n t o o k a b o u t

40 h o u r s a n d was f o l l o w e d b y a f u r t h e r 2 h o u r s *

stirrin g .

Most o f t h e c a r b o n d i s u l p h i d e was t h e n d i s t i l l e d o f f and t h e r e s i d u e t r e a t e d w i t h a b o u t 750

g. ic e .

d i s t i l l e d u n t il th e d i s t i l l a t e

was c l e a r ( 2 . 5 1 . ) , t h e d i s ­

tilla te

s a t u r a t e d w i t h s a l t and e x t r a c t e d w i t h e t h e r .

Y i e l d , 1 5 .9 g . 1 5 .3 6 g . (lit. i

T h is was t h e n s te a m

b . 1 4 3 ° /l6 .5 m m .

(9 0 $ ).

b . 7 8 ° / 0 . 2 mm. ( 8 7 . 5 $ ) .

R e d is tille d

Semic a rb az one m. 2 1 0 -2 1 3 °

b . 1 3 8 - 1 3 9 ° / l 2 mm., s e m ic a r b a z o n e m. 216° ( 2 0 6 - 2 0 7 ° ) )

A tte m p te d o y c l i s a t i o n o f p h e n y l - v a l e r i c

a c id w ith hydrogen

flu o rid e . 5 g . c r u d e p h e n y l v a l e r i c a c i d was d i s s o l v e d i n 15 ml h y d r o g e n f l u o r i d e and l e f t 1 0 h o u r s . unchanged.

The a c i d w as r e c o v e r e d

O y c l i s a t i o n o f p h e n y l ^ v a l e r y l o h l o r i d e w i t h HP. P h e n y l v a l e r y l c h l o r i d e ( 5 g . ) was m ix ed w i t h a n ­ h y d r o u s HP { oq . 15 m l . )

and a llo w e d t o s t a n d o v e r n i g h t .

A f t e r e v a p o r a t i o n o f t h e HP, t h e r e s i d u e was e x t r a c t e d w i t h HagCO

and t h e a l k a l i i n s o l u b l e p o r t i o n s e p a r a t e d . T h is 3 l a t t e r g a v e a brow n o i l ( 0 .5 6 7 g . t 14$) w h ich g a v e a s e m i-

o a r b a z o n e i d e n t i c a l w i t h t h a t fro m b e n z o s u b e r o n e ( m .p . and m ix e d m . p . ) .

P h e n y l v a l e r i c a c i d was r e c o v e r e d on a c i d i f y ­

i n g t h e Ha^GO^ e x t r a c t . C o n d e n s a t i o n o f b e n z o s u b e r o n e and e t h y l s u c c i n a t e ;

k e to -

h e x a h y d r o b e n z a z u l e n e . 5cvcy n A m ix tu re o f b e n zo su b ero n e (2 3 .1 g .)

and e t h y l

s u c c i n a t e (4 5 g . ) was a d d ed t o a c h i l l e d s o l u t i o n o f p o t a s s i u m (8 g . ) i n t - b u t y l a l c o h o l (160 m l . ) .

A fter re flu x in g under

n i t r o g e n f o r 45 m i n u t e s and w o r k in g up a s d e s c r i b e d above t h i s g a v e t h e o r u d e h a l f - e s t e r XXXI ( 3 9 . 2 g . = 9 5 $ ) , w h ic h was o y c l i s e d w i t h o u t f u r t h e r p u r i f i c a t i o n b y r e f l u x i n g h o u r s u n d e r n i t r o g e n w i t h a o e t i o a n h y d r i d e (4 0 0 m l . ) , g l a c i a l a c e t i c a c i d (2 0 0 m l . )

and f u s e d z i n c c h l o r i d e (4 g . ) .

T h i s w as w o rk e d up a s f o r k e t o o o t a h y d r o a z u l e n e ,

and d i s ­

t i l l a t i o n o f t h e n e u t r a l r e s i d u e gave a w h ite c r y s t a l l i n e s o l i d , m . p . 5 9 -6 1 ° ( 6 . 5 7 g . ) w h ic h d i s t i l l e d a t 1 4 3 - 1 4 8 ° / 0 . 4 mm.

T h is w as r e o r y s t a l l i s e d from p e t r o l e u m ( 4 0 - 6 0 ° )

and t h e n a q . a l c o h o l ;

w h i t e n e e d l e s , m .p . 6 1 - 6 2 ° (XXXII) .

(P oun ds

0, 8 4 .9 1 ,

H, 7 .0 1 $ ;

C ^ H ^ O r e q u i r e s C, 8 4 . 8 4 ,

H, 7 . 0 7 $ ) . T h is k e t o n e g a v e a s e m io a r b a z o n e w h ic h c r y s t a l l i s e d fro m a lQ o h o l i n s o f t s p h e r i c a l c l u s t e r s o f n e e d l e s s i n t . 2 2 7 - 2 3 0 ° , deootnp. 2 3 6 ° .

(J?ound, C, 6 9 . 7 3 , H, 6 . 4 7 , H, 1 6 .6 3 ^

°X5H170H3 r e 4 a l r e s °* 7 0 .6 0 , H, 6 . 6 7 , H, 1 6 . 4 7 $ ) . S u b lim a tio n o f th e r e s id u e s l e f t a f t e r d i s t i l l i n g t h e k e t o n e g a v e a few mg. y e ll o w p r i s m s s u b l . 1 5 5 - 1 6 0 ° / 0 . 4 mm. R e c j r y s t a l l i s a t i o n fro m e t h a n o l g av e c o l o u r l e s s p r i s m s , m .p . 1 99 -201°.

(P oun d, C, 7 5 .4 2 , H, 5 . 6 5 $ ) .

T h i s compound ga v e

a 2 : 4 - d i n i t r o p h e n y l h y d r a z o n e , b u t o n l y on l o n g s t a n d i n g , and i t was n o t i n v e s t i g a t e d f u r t h e r . The a l k a l i s o l u b l e p r o d u c t s w ere e x t r a c t e d w i t h HaHCOg t o rem ove a c i d s , and t h e r e s i d u e , w h ic h h a d a p h e n o l i c s m e l l , was s o l u b l e i n HaOH.

An e t h e r e a l s o l u t i o n h o w e v er

g a v e no c o l o u r a t i o n w i t h a q . P e O l ^ . I n a n o th e r c y c l i s a t i o n ,

a f t e r th e a lk a li tre a tm e n t

t h e n e u t r a l p r o d u c t was e x t r a c t e d w i t h OHClg.

The f i r s t

e x t r a c t was d a r k brow n and c o n t a i n e d m o s t o f t h e p r o d u c t , b u t s u b s e q u e n t e x t r a c t s h a d a d e ep b l u e - v i o l e t c o l o u r . T r i a l c h ro m a to g ra m s o f t h i s s o l u t i o n w e re m ade, b u t on s i l i o a no a b s o r p t i o n t o o k p l a c e , w h i l e on a lu m i n a a v i o l e t b a n d w as fo rm e d w h ic h c o u l d n o t be e l u t e d .

O th e r a t t e m p t s

a t i s o l a t i n g t h e c o l o u r i n g m a t t e r w ere u n s u c c e s s f u l , and on

s t a n d i n g f o r 2 -3 d a y s ( i n t h e d a r k ) t h e c o l o u r v a n i s h e d . T h is e x p e r i e n c e was n o t r e p e a t e d i n o t h e r p r e p a r a t i o n s . A tte m p te d d e h y d r o g e n a t i o n o f t h e k e t o n e XXXTI. The t r i o y c l i c k e t o n e ( 0 . 3 g . ) was h e a t e d i n a s e a l e d t u b e w i t h s e l e n i u m ( 0 .3 6 g . ) f o r 26 h o u r s a t 3 0 0 - 3 5 0 ° . E x t r a c t i o n o f th e p ro d u c t gave o n ly a y e llo w o i l w ith a g r e e n f l u o r e s c e n c e (25 m g . ) . R e d u c t i o n o f t h e k e t o n e XXXII. ( i ) . A lum inium l s o p r o p o x i d e . The t r i c y c l i c k e t o n e (1 g . )

and d i s t i l l e d a lu m in iu m

i s o p r o o o x i d e ( 3 g . ) w ere d i s s o l v e d i n d r y t o l u e n e ( o a 20 m l . ) and r e f l u x e d f o r Z \ h o u r s .

A f t e r w a s h in g f r e e fro m

a lu m in iu m s a l t s t h e p r o d u c t was d i s t i l l e d and t h r e e f r a c t i o n s o o lle o te d i( a ) p a l e y e l l o w o i l b . 9 5 ° / 0 . 1 mm.

(found:

C, 9 1 . 3 0 ,

H, 7 . 6 9 $ ) . ( b ) b r i g h t o r a n g e o i l b . 1 2 0 ° / 0 . 1 mm.

(found:

C, 8 8 .0 2 ,

H, 7 . 4 7 $ ) . (o )

c r y s t a l s s u b l . 1 4 0 - 1 5 0 ° / 0 . 1 mm., r e o r y s t a l l i s e d fro m

o v c l o h e x a n e . m .p . 1 2 3 - 1 2 4 ° .

(found:

0 , 8 5 . 1 7 , H, 7 . 3 5 $ ) .

The f i r s t two a p p e a r t o b e m i x t u r e s o f t h e h y d ro o a r b o n XXXVIII (C14H1 4 r e q u i r e s 0 , 9 2 . 3 5 , H, 7 .6 9 $ ) a n d t h e c a r b i n o l XXXIX (C14H1 6 0 r e q u i r e s C, 8 4 . 0 0 , H, 8 . 0 0 $ ) .

( i i ) . P t 02 h y d r o g e n a ti o n . The t r i c y c l i c k e t o n e (2 g . ) was d i s s o l v e d i n g l a c i a l a c e tic

a c i d (15 m l . )

c a t a l y s t (2 0 m g . ) .

a n d h y d r o g e n a t e d o v e r Adams' EfOg A b s o r p t i o n t o o k p l a c e a t 100 m l . / h r .

u n t i l 1 d o u b le b a n d h a d b e e n s a t u r a t e d ;

it

t h e n slo w e d to

40 m l . / h r . u n t i l 2 d o u b l e b o n d s h a d b e e n s a t u r a t e d and t h e n a b s o r p t i o n was v e r y slo w u n t i l a f t e r 16 h o u r s , 3 m o l e c u l e s Hg h a d b e e n a b s o r b e d a n d a b s o r p t i o n s t o p p e d . The p r o d u c t on d i s t i l l a t i o n g a v e two f r a o t i o n s : ( a) m o b i l e , c o l o u r l e s s b . 1 0 5 - 1 1 0 ° / 0 . 6 mm. ( 1 . 1 4 g . ) (found:

C, 8 6 . 7 0 , H, 9 .0 8 $ )

(b) v i s c o u s , c o l o u r l e s s b . 1 1 5 - 1 2 0 ° / 0 . 6 mm. ( 0 . 7 2 g . ) (found:

C, 8 2 . 4 2 , H, 8 . 4 4 $ ) . T hese a r e p r o b a b l y m i x t u r e s o f th e s a t u r a t e d h y d ro ­

carb on and o a r b in o l c o r r e s p o n d i n g t o XXXVIII and XXXIX re sp e c tiv e ly . (°14H18 r e ^a i r e s G» 9 0 .3 3 , H, 9.68$*

C ^H ^O re q u ire s

C, 8 3 . 1 6 , H, 9 .7 8 $ ) . ( i i i ) . R an ey n i c k e l h y d r o g e n a t i o n . The t r i c y c l i c k e t o n e ( 1 g . ) was h y d r o g e n a t e d i n (79 ) a l c o h o l s o l u t i o n o v e r R aney n i c k e l ( P a v l i c and A d k in s ). A b s o r p t i o n s t o p p e d a f t e r 5 h o u r s , when 2 m o l s . h y d r o g e n h a d been absorbed.

The p r o d u c t was d i s t i l l e d and ga v e an

a p p a r e n t l y hom og en eo us, v e r y v i s c o u s l i q u i d b . 1 0 5 ° / 0 . 2 mm.

(Sou nd !

C, 8 0 .7 0 , H, 7 .9 3 f ) .

D e h y d r o g e n a ti o n o f t h e r e d u c t i o n p r o d u c t s . The low b o i l i n g f r a c t i o n ( a) o f t h e ^ tO ^ r e d u c t i o n p r o d u c t ( 0 . 8 4 g . ) was h e a t e d u n d e r r e f l u x w i t h s e l e n i u m (1 g . )

a t 3 3 0 -3 6 0 ° f o r 3 d a y s .

The m a t e r i a l became v e r y

d a r k brow n and t a r r y and was e x t r a c t e d w i t h CHG1_, t h e ext r a c t b e i n g c h ro m a to g r a p h e d on a s h o r t a lu m in a colum n t o rem ove Q o l l o i d a l s e l e n i u m .

A fte r e v a p o ra tio n o f th e so lv e n t

t h e r e s i d u e was e x t r a c t e d i n a S o x h l e t w i t h p e t r o l e u m b u t t h e e x t r a c t was o n l y l i g h t o r a n g e i n c o l o u r ( g r e e n f l u o r e s c e n c e D e h y d r o g e n a ti o n o f t h e same m a t e r i a l w i t h p a l l a d i u m b l a c k a t 3 2 0 - 3 3 0 ° f o r 4^- h o u r s and d i s t i l l a t i o n o f t h e p r o d u c t ga v e o n l y a c o l o u r l e s s d i s t i l l a t e . D e h y d ro g e n a tio n o f th e m ix tu re o f p r o d u c t s w i t h s u l p h u r (7 5 $ o f t h e o r e t i c a l ) to t h e e v o l u t i o n o f Hg S .

re d u c tio n a t 2 2 0 -3 0 0 ° l e d

On d i s t i l l a t i o n some s t a r t i n g

m a t e r i a l was r e c o v e r e d , b u t e x t r a c t i o n o f t h e r e s i d u e w i t h CHGlg, e v a p o r a t i o n o f t h e s o l v e n t , e x t r a c t i o n o f t h e r e s i d u e w i t h p e t r o l e u m a n d c h ro m a to g r a p h y o f t h i s s o l u t i o n on a lu m i n a g a v e a p i n k b a n d on t h e c o lu m n .

T h is w as e l u t e d

w i t h b e n z e n e - p e t r o l e u m t o g i v e a d a r k r e d s o l u t i o n vfcich d id not have an a zu len e s p e o tru a , b u t had a s tro n g a b s o r p tio n b a n d a t 5428 1 .

Ho t r i n i t r o b e n z e n e c o m p le x o f t h i s m a t e r i a l

c o u ld be o b ta in e d . The R aney n i c k e l r e d u c t i o n p r o d u c t was r e f l u x e d w ith se len iu m a t p a 4 0 0 ° fo r 5 h o u r s . w as f a i r l y v i g o r o u s a t f i r s t ,

E v o l u t i o n o f H^Se

b u t t h e p r o d u c t was v i s c o u s

a nd t a r r y and g a v e no a z u l e n e . T h is r e d u c t i o n p r o d u c t was a l s o v a p o u r i s e d o v e r 10$ p a l l a d i u m c h a r c o a l i n t h e v a p o u r p h a s e a p p a r a t u s A a t 4 3 0 ° b u t t h e d i s t i l l a t e s w e re c o l o u r l e s s .

A d d itio n o f d ia z o a c e tic e s t e r to 2 -m e th y lin d a n e . To 2 - m e t h y l i n d a n e (6 8 g . ) i n a O l a i s e n f l a s k was added d i a z o a o e t i o e s t e r (1 0 g . ) d a r i n g 1 h o u r , t h e t e m p e r a ­ tu r e b e in g m a in ta in e d a t 1 3 0 -1 4 0 °. o f gas to o k p la c e .

A v e r y slo w e v o l u t i o n

The t e m p e r a t u r e was r a i s e d t o 165°

d u r i n g 15 m i n u t e s , t h e e v o l u t i o n o f g a s b e c o m in g more v i o l e n t , a n d was m a i n t a i n e d t h e r e f o r 2 h o u r s .

The u n ­

c h a n g e d in d a n e was d i s t i l l e d an d r e - t r e a t e d w i t h m ore d i a z o a c e tic e s te r ,

a t o t a l o f 14 a d d i t i o n s b e i n g made u s i n g 83 g .

d ia z o a o e tic e s t e r .

1 6 .2 g . i n d a n e was r e o o v e r e d b . *£1.125°/

15 mm. The a d d i t i o n p r o d u c t was now d i s t i l l e d and g a v e (1 ) 8 . 5 g .

b . ^ C . 1 4 0 ° / 4 mm.,

(3 ) 5 . 3 g .

b.

(2 ) 3 4 .7 g .

1 6 5 - 1 7 5 ° / 4 mm.,

b.

1 4 0 - 1 5 5 ° / 3 mm.

(4 ) 5 7 .4 g . r e s i d u e .

H y d ro ly sis of th e a d d itio n p ro d u c t. The a d d i t i o n p r o d u c t ( m id d le f r a c t i o n , 22 g . ) was r e f l u x e d 14 H o u rs w i t h a l c o h o l i c p o t a s h (1 7 5 m l. 96$ EtOH, 19 m l . H2 0 and 1 1 . 5 g . KOH) .

The a l c o h o l w as d i s t i l l e d

and t h e r e s i d u e d i l u t e d w i t h w a t e r and e x t r a c t e d w i t h e t h e r . T h is g a v e o n l y o a 30 mg. r e s i d u e on e v a p o r a t i o n ;

a c id ific a ­

t i o n o f th e a l k a l i n e l a y e r fo llo w e d by e x t r a c t i o n gave th e c ru d e a c id (1 8 .1 2 g . ,

v i s c o u s brow n l i q u i d ,

9 5$).

D e h y d r o g e n a ti o n o f h y d r o l y s e d a d d i t i o n p r o d u c t : 2 - m e t h y l a z u le n e . The a c i d 1.19 g . ) w as d e h y d r o g e n a t e d o v e r 10$ p a l l a d i u m c h a r o o a l s u p p o r t e d on a s b e s t o s , v a p o u r p h a s e a p p a r a t u s ( d ia g r a m C ) .

a t 2 8 0 -3 0 0 ° i n t h e

The p r o d u c t w as d i s ­

s o l v e d i n p e t r o l e u m and e x t r a c t e d w i t h 85$ HgPO^, w h ic h was t h e n w a sh e d w i t h p e t r o l e u m , d i l u t e d w i t h w a t e r an d e x t r a c t e d w ith e th e r .

The e t h e r was t h e n w ash ed w i t h Ha^CO^ s o l u t i o n

t o rem ove a c i d s .

T h is g a v e 0 .9 1 g . m a t e r i a l , w b i l e 1 .4 7 g .

n e u t r a l m a t e r i a l r e m a in e d i n t h e e t h e r .

9 .4 2 g . r e m a in e d

i n s o l u b l e i n HgPO^. The n e u t r a l f r a o t i o n was d i s s o l v e d i n p e t r o l e u m and c h r o m a to g r a p h e d on 25 g . a lu m i n a ( a c t i v i t y I I - I ) , w a s h in g w ith p e tro le u m b e in g c o n tin u e d u n t i l th e v i o l e t c a l c a r ohanged to b l u e .

E v a p o r a t i o n g a v e 2 - m e th y l a z u l e n e ( 1 . 0 6 g . )

w h ic h c r y s t a l l i s e d on c o o l i n g .

R e o r y s t a l l i s e d fro m a q . a l c o h o l , b l u e - v i o l e t l e a f ­ l e t s m.p* 4 6 . 5 ° ( o o r r . ) . a a l e . t o r Ci :lH1 0 : S p e c tru m :

(P o u n d :

C, 92*12, H, 7 .3 9 $ ;

C, 9 2 . 9 1 , H, 7 .0 9 $) .

673 f f , 649 s , 610*5 f f ,

590 m, 562 f f ,

523 s s

(p etro leu m ). The t r i n i t r o b e n z e n e co m p lex c r y s t a l l i s e d f r o m a l ­ c o h o l i n b ro w n n e e d l e s , m . p . 1 4 1 -1 4 2 ° ( o o r r . ) . (P o u n d :

0, 5 7 .4 3 , H, 3 . 6 3 $ ;

c a lc , for

:

G, 5 7 .4 6

H, 3 . 6 9 $ ) . D e h y d ro g en a tio n o f u n h y d ro ly se d a d d i t i o n p ro d u c t:

2 -m eth y l -

a z u le n e - 6 - c a r b o x y lic e s t e r , X L II. The a d d i t i o n p r o d u c t (m id d le f r a c t i o n : 4 2 .8 g . ) w as d eh y d ro g en ated i n

th e vapour p h ase a p p a ra tu s o v er p a lla d iu m

c h a r c o a l (10$) on a s b e s t o s a t 3 0 0 -3 1 0 ° d u r i n g

ca 3 h o u rs.

A

d e e p b l u e c o n d e n s a t e ( 3 9 . 1 g . ) w as o b t a i n e d and e x t r a o t e d w i t h HgPO^, g i v i n g a g r e e n i s h bro w n n e u t r a l f r a c t i o n ( 8 . 1 g . ) some a c i d i c m a t e r i a l e x t r a o t a b l e w i t h Ha^CO^ (1 0 0 m g.) and 30 g . HgPO^ i n s o l u b l e m a t e r i a l . The n e u t r a l m a t e r i a l was e x t r a c t e d w i t h p e t r o l e u m and c h r o m a to g r a p h e d on a l u m i n a (8 0 g . ) .

A b l u e o i l was

o b t a i n e d ( 3 . 2 g . ) w h ic h was r e - o h r o m a t o g r a p h e d and t h e n d i s t i l l e d , b . p . 1 3 0 ° / 0 . 1 mm. ( 2 . 2 4 g . ) . H, 6 . 6 9 $ j

C14H1 4 02 r9(l a i r 9 a :

S peotrum s

752 f ,

716 m, 670 m, 653 f ,

572 m,

560 s ,

( i'o a n d i

78

0 , 7 7 .9 9 ,

6 .5 9 $ ).

628 m, 614 m, 594 f f ,

549 f ( p e t r o l e u m ) .

The t r i n i t r o b en zen e d e r i v a t i v e fo rm ed bro w n n e e d l e s m.p# 6 5 - 6 5 . 5 ° , w b ich w ere more s o l u b l e i n a l c o h o l t h a n trin itro b e n z e n e i t s e l f . C J L „ 0 oI _ r e q u i r e s ! 20 I f

o 3

(Pound*

G,

5 6 .2 7 , H , 3 . 9 6 , H, 9 .8 8

C, 5 6 .2 1 , H, 4 . 0 1 , H, 9 . 8 3 $ ) .

A d e a n s e p a r a t i o n o f e s t e r fro m t r i n i t r o b e n z e n e o o u l d n o t b e o b t a i n e d b y c h r o m a to g r a p h y on n e u t r a l o r a l ­ k a l i n e a lu m in a , u s i n g p e t r o l e u m , b e n z e n e o r c y o lo h e x a n e a s s o l v e n t s s i n o e t h e two co m p o n e n ts w e re a d s o r b e d w i t h a p p r o x i m a t e l y t h e same s t r e n g t h . I n o th e r p r e p a r a tio n s of th e e s t e r , t r a c e s o f th e v i o l e t 2 - m e t h y l a z u l e n e w ere o b t a i n e d , and a l s o a b l u e m a te ria l.S p e o tru m *

722 f f ,

686 m, 649 f f ,

561 s , 538 s , 524 s s ,

616 m, 587 f f , 506 s s ( 2 - m e t h y l -

a z u le n e -5 -c a rb o x y lic e s t e r ? ) . H y d ro ly s is o f 2 - m e th y la z u le n e -6 -o a rb o x y lic e s t e r - 2 -m eth y l a z a l e n e - 6 - o a r b o x y l i o a c i d XLV. The e s t e r ( 5 3 0 m g.) w as r e f l u x e d 3 h o u r s w i t h a l cob&io p o t a s h (1$*

30 m l . ) .

W a te r w as a d d e d , t h e a l c o h o l

d i s t i l l e d , and t h e s o l u t i o n e x t r a c t e d w i t h e t h e r , w h ic h rem o ved o n l y a t r a c e o f g r e e n m a t e r i a l .

The a q u e o u s l a y e r

o n a c i d i f i c a t i o n g ave a d a r k g r e e n s o l i d (3 8 0 m g .) w h ic h o r y s t a l l i s e d from a l a r g e volume o f c y o l o h e x a n e i n d a r k b l u e - g r e e n c r y s t a l s m .p . 1 6 4 - 1 6 5 ° . H, 5 . 0 9 $ (

c 12H10 02

re q u ire s!

(Pound*

G, 7 6 .8 2 ,

C, 7 7 . 4 0 , H, 5 . 4 1 $ ) .

Spectrum *

654 f f ,

631 s , 594 f f ,

574 s ,

550 m. ( a l o o h o l ) .

A tte m p te d p r e p a r a t i o n o f a c i d c h l o r i d e and amide fro m 2m e th y la z u le n e -6 -o a rb o :x y lio a c i d . The a c i d (1 5 0 m g.) was d i s s o l v e d i n d r y e t h e r (1 0 m l . ) a n d t h i o n y l c h l o r i d e ( 0 . 1 5 m l . ) i n d r y e t h e r (5 m l . ) a d d e d w ith sh a k in g .

A fte r sta n d in g \ h o u r i n th e c o ld , th e s o lu tio n

w h ich w as now d e ep r e d , was p o u r e d i n t o o f ammonia (1 0 m l . ) w i t h c o o l i n g i n i c e .

an e t h e r e a l s o l u t i o n A .g re e n p r e c i p i t a t e

fo rm e d , i n s o l u b l e i n s o l v e n t s o t h e r t h a n a l c o h o l s .

The

s o l u t i o n was e v a p o r a t e d and t h e r e s i d u e and p r e c i p i t a t e d i s ­ s o l v e d i n m e t h a n o l / e t h e r and c h r o m a to g r a p h e d on a l u m i n a .

A

s m a l l amount o f t h e o r i g i n a l a c i d ( i d e n t i f i e d b y s p e c tr u m ) was r e c o v e r e d b y e l u t i o n w i t h ammonia, b u t t h e m a j o r i t y o f t h e m a t e r i a l c o u l d n o t b e e l u t e d from t h e a l u m i n a . A tte m p te d p r e p a r a t i o n o f t h e amide fro m t h e e s t e r . The e s t e r (5 5 m g .) w as d i s s o l v e d i n e t h a n o l (2 m l . ) , t h e s o l u t i o n s a t u r a t e d v d t h ammonia g a s a n d a llo w e d t o s t a n d 5 days i n th e c o ld .

A p o r t i o n w as t h e n e v a p o r a t e d b u t t h e

r e s i d u e was l i q u i d .

A f t e r a f u r t h e r 2 days th e s o l u t i o n

was r e f l u x e d 3 h o u r s and t h e n e v a p o r a t e d , b u t t h e r e s i d u e was s t i l l l i q u i d and s o l u b l e i n p e t r o l e u m .

C h ro m a to g ra p h y on

a lu m i n a showed t h a t t h e m a t e r i a l w as p r a c t i c a l l y hom ogeneous,

o n l y a t r a c e r e m a i n i n g on t h e oolum n a f t e r w a s h in g w i t h benzene.

The s p e o tr u m o f t h e e l u a t e was i d e n t i c a l w i t h

t h a t o f th e s t a r t i n g m a te r ia l. 2 - M e t h y l a z u l e n e - 6 - c a r b o x y l i c amide

aL

III.

The e s t e r (1 5 5 m g.) was d i s s o l v e d i n 9 6 $ e t h a n o l ( o a 1 m l.)*

a few d r o p s o f e t h y l e n e g l y c o l a d d e d , t h e

s o l u t i o n s a t u r a t e d w i t h ammonia g a s and h e a t e d 23 h o u r s a t 190° i n a s e a le d tu b e .

The a l o o h o l w a s t h e n e v a p o r a t e d ,

t h e r e s i d u e d i s s o l v e d i n OHOlg an d w a sh e d w i t h d i l . ffagGOg s o l u t i o n w h ic h rem oved some b l u e - g r e e n a c i d (3 0 m g . ) . S pectrum *

652 m ( 6 2 8 ? ) ,

595 f ( 5 7 2 ? )* 549 f .

The CHGlg l a y e r was e v a p o r a t e d and g a v e a s o l i d r e s i d u e (1 0 0 mg. = 7 6 $ ) .

T h i s w a s s e p a r a t e d i n t o two

f r a c t i o n s b y c r y s t a l l i s a t i o n from e t h a n o l * 1 ) . v i o l e t p l a t e s m .p . 2 2 5 -2 2 7 ° ( s m a l l q u a n t i t y ) (P o u n d :

C, 7 2 . 3 4 , H,

6 .0 3 , I , 8 .5 3 $ ) ,

2 ) . b l u e p l a t e s m . p . 2 1 2 -2 1 4 ° (m a in f r a c t i o n ) (P o u n d : q u ire s* S pectrum *

664

C, 7 7 .9 2 , H,

5 . 9 9 , ff, 7 .6 1 $ ;

C, 7 7 .8 4 , H,

5 . 9 5 , ff, 7 . 5 7 $ ) .

m ( 6 4 2 ? ) , 606 f ( 5 8 3 ? ) , 557 f

C12H1;]Off r e ­

(a lo o h o l).

S u b s e q u e n t p r e p a r a t i o n s i n w h ic h 99$ e t h a n o l was s u b s t i t u t e d f o r 96$ w ere u n s u c c e s s f u l . I n an e a r l y e x p e r i m e n t , c o n d u c t e d a t 1 40° f o r 6| ” h o u r s ,

a b r i g h t g r e e n a c i d was o b t a i n e d , m .p . 2 1 5 -2 2 0 °

d e co m p .;

m ixed w i t h t h e d a r k b l u e - g r e e n a c i d ( m . p . 1 6 2 - 1 6 4 ° )

fro m t h e h y d r o l y s i s o f t h e e s t e r m .p . c^a 160 Speotrum *

o

decom p.

669 m, 607 m, 558 s . On t r e a t m e n t w i t h d ia z o m e th a n e t h i s g a v e a b l u e

so lid e ste r

s p e o tr u m :

(5 6 4 s s ) , ( 5 4 2 ? )

676 f , 651 s , 636 s , 613 m, (577 s s ) ,

(p e tro le u m ).

The b y p r o d u c t from l a t e r amide p r e p a r a t i o n s a p p e a r e d t o b e a m i x t u r e o f t h e two a o i& s . A tte m p te d Hofmann r e a c t i o n on 2 - m e t h y l a z u l e n e - 6 - c a r b o x y l i c a m id e. A s t o c k s o l u t i o n o f 0 . 5 ff ffaOCl was p r e p a r e d b y a b s o r b i n g t h e c h l o r i n e fro m 21 m l . HC1 and 1 .6 1 5 g . KMhO^ i n 100 m l . 10$ HaOH ( s e e Adams:

O rg a n ic R e a c t i o n s , v o l . I I I ) .

The e f f e c t o f t h i s s o l u t i o n o n g u a j a z u l e n e was t r i e d b y d i s ­ s o l v i n g 100 m g. o f t h e l a t t e r i n 1 m l . d i o x a n e , a d d in g 2 m l . ffaOCl s o l u t i o n and a l l o w i n g t h i s to s t a n d a t 3 0 - 4 0 ° f o r Z\

hours.

The a z u l e n e was r e c o v e r e d u n c h a n g e d . The c r u d e amide T175 m g .) w as k e p t a t 3 5° f o r 2 h o u r s

w i t h 0 . 5 ff ffaOCl s o l u t i o n (4 m l . ) . s o lv e , b u t tu r n e d brow n.

The s o l i d d i d n o t d i s ­

So HC1 s o l u b l e m a t e r i a l was

o b t a i n e d and m ost o f t h e amide (1 20 m g .) was r e o o v e r e d . T h is r e c o v e r e d amide (1 2 0 m g.) was d i s s o l v e d i n

m e t h a n o l ( c a 5 m l . ) , ffaOCl s o l u t i o n ( 2 . 7 m l . )

added and t h e

m i x t u r e warmed on t h e w a t e r b a t h f o r a few m i n u t e s .

The

o o l o u r r a p i d l y c h a n g e d t o p u r p l e and a brow n gum w as d e ­ p o site d .

A f t e r c a 10 m i n u t e s t h e m i x t u r e was d i l u t e d w i t h

w a t e r and t h e m e t h a n o l d i s t i l l e d .

The a q u e o u s l a y e r was

e x t r a c t e d w i t h e t h e r and t h e n GHC1_, t h e n a c i d i f i e d a n d e x 3

tr a c te d ag ain .

The l a t t e r e x t r a c t gave some b l a c k s o l i d

(7 0 m g.) w h ic h o n r e o r y s t a l l i s a t i o n fro m o y c l o h e x a n e g a v e g r e e n c r y s t a l s m .p . 1 5 5 - 1 6 0 ° (4 1 m g.) a p p a r e n t l y i d e n t i c a l v / it h 2 - m e t h y l a z u l e n a - 6 - c a r b o x y l i c a c i d . The f i r s t

e x t r a c t ( p u r p l e ) ga v e a d a r k p u r p l e s o l i d

(5 0 m g.) w h ic h was d i s s o l v e d i n a l i t t l e

e t h a n o l and t r e a t e d

w i t h d i l . HgSO^, b u t no o o l o u r e d a c i d s o l u b l e m a t e r i a l w as o b tain ed *

The o r i g i n a l m a t e r i a l was r e c o v e r e d and c h r o m a to ­

g r a p h e d g i v in g * 1 ) b l u e o i l (1 0 m g.) 2) p i n k , s e m i - s o l i d (3 0 m g.) 3 ) g r e e n - b r o w n , gum ( t r a c e ) 4) b l u e s o l i d (1 0 m g.) - u n c h an g e d a m id e . A tte m p te d r e d u c t i o n o f t h e a s i d e w i t h l i t h i u m a lu m in iu m h y d rid e . The amide was t r e a t e d w i t h e x c e s s LiAlH^ i n e t h e r and a b ro w n co m p lex was fo rm e d , b u t on h y d r o l y s i n g t h i s no

a o i d s o l u b l e m a t e r i a l was o b t a i n e d , t h e s t a r t i n g m a t e r i a l b e in g re c o v e re d unchanged. to in c re a s e s o l u b i l i t y ,

When some d r y b e n z e n e w a s a d d e d

and t h e s o l u t i o n warmed f o r a few

m i n u t e s , a t r a c e o f p i n k m a t e r i a l s o l u b l e i n a c i d w as o b t a i n e d , b u t t h e b u l k o f t h e amide was r e c o v e r e d u n c h a n g e d .

When

t h e r e a c t i o n was p e r f o r m e d i n b e n z e n e and t h e c o m p le x r e f l u x e d 2 h o u r s , t h e b l u e o o l o u r w as d e s t r o y e d c o m p l e t e l y and no a c i d s o l u b l e m a t e r i a l was o b t a i n e d , a b ro w n gum r e m a i n i n g i n th e n e u tr a l f r a c tio n o f th e p ro d u ct. R e d u c t i o n o f 2 - m e t h y l a z u l e n e - 6 - c a r b o x y l i c e s t e r w i t h L iA lH ^i 2 - m e t h y l - 6 - h y d r o x y m e t h y l a z u l e n e , X L V I I I. The e s t e r (2 0 0 mg#) d i s s o l v e d i n d r y e t h e r ( o a 20 m l . ) was p l a c e d i n a f l a s k f i t t e d w i t h c o n d e n s e r a n d d r o p p i n g fu n n e l p r o te c te d by d ry in g tu b e s . J iA lH * ( 3 . 5 m g . / m l .

An e t h e r e a l s o l u t i o n o f

i 4 m l . ) was d ro p p e d i n w i t h s h a k i n g .

A

p u r p l e com plex was d e p o s i t e d and a ll o w e d t o s t a n d o v e r n i g h t * A few d r o p s o f w a t e r w e r e t h e n a d d e d , t h e e x c e s s rem oved w i t h UagSO^ and t h e s o l u t i o n f i l t e r e d

and e v a p o r a t e d .

The

r e s i d u e ( v i o l e t ) was o n l y s p a r i n g l y s o l u b l e i n p e t r o l e u m and was d i s s o l v e d i n b e n z e n e and c h ro m a to g r a p h e d g i v i n g : 1)

a tra c e

t

b lu e

611 m, 591 m, 575 f , a zu len e?)

* s p e c tr u m 692 f f ,

559 s ,

542 s ,

670 m, 649 s ,

532 s ( 2 : 6 - d i m e t h y l -

626 f f ,

2) 80 mg. * b l u e - v i o l e t 578 s ,

551 f ,

* s p e o tru m 658 f ,

635 s ,

599 f ,

511 s s (u n c h a n g e d e s t e r )

3) 125 mg. : v i o l e t ( e l u t e d w i t h e t h e r )

:

s p e o tr u m 654 s s ,

601 m, 561 m. R e c r y s t a l l i s a t i o n o f f r a c t i o n 3 from c y c l o h exane g av e d a r k p u r p l i s h b l a c k p r i s m s o f 2 - m e t h y l - 6- h y d r o x y m e t h y la z u l e n e m .p . 1 2 4 - 1 2 5 ° . (Pound*

0 , 8 3 .4 4 , H,

C12H1 2 ° m a i r e a *

C,

7 .2 3 ,

nH,f ( S e r e w i t i n o f f ) 0 .6 1 $ ;

8 3 . 6 9 , H, 7 . 0 2 , "Hw 0 . 5 9 $ ) .

S im ila r re d u c tio n of th e f r e e 2 -m e th y la z u le n e -6 o a r b o x y l i c a c i d gave a v i o l e t o i l b u t t h e p r o d u c t was n o t o ry s ta llis e d . A subsequent e x c e s s o f LiAlH^ gave

r e d u c t io n o f th e e s t e r u sin g a l a r g e no u n c h a n g e d e s t e r , b u t much

g r e e n brow

by p ro d u c t. T r e a tm e n t o f t h e a l o o h o l w i t h b e n z o y l c h l o r i d e and p y r i d i n e i n e t h e r g a v e a b l u e - v i o l e t o i l w h ic h c o u l d n o t b e o ry sta llise d .

The r e a c t i o n w as f a i r l y v i g o r o u s and t h e

a lo o h o l does n o t ap p ear to be v e ry s ta b le as i t r e s i n i f i e s re a d ily in a ir .

70.

T a b le o f S p e o t r a These s p e c t r a w e re m e a s u re d on a v i s u a l s p e c t r o ­ m e t e r , t h e o e n t r e s o f thA b a n d s b e i n g t a k e n as t h e a v e r a g e o f a num ber o f d e t e r m i n a t i o n s . Wave l e n g t h s a r e i n mp and t h e i n t e n s i t i e s o f t h e b a n d s a r e d e n o te d q u a l i t a t i v e l y a s f o l l o w s : f f = v e r y s t r o n g , f - s t r o n g , m * medium, s - w eak, s s B v e r y weak 2 E ste r X L II

(P e tr.)

3

4

5

6

A c id (fr o m am ide p re p .)

E ste r (fro m a c i d 3)

Amide X L II I

A lc o h o l XLV I I I

(EtOH) (EtOH)

(E th e r)

(EtOH)

(E th e r)

A c id XLV

7

8

2- M e th y l H ydro a zu len e o arb o n (fro m e s t e r + LiAlH4 ) XLIX (P e tr.) (P e tr.)

751 f 716 m 692 f f 669 m.

670 m 653 f

654 f f

676 f

664 m 654 s s

651 s

673 f f

670 m

649 a

649 s

(64 2 ?) 628 m 614 m

626 f f

636 S

631 s 607 m

613 m

606 m

611 f f

611 m

590 m

591 m

601 m 594 f f

594 f f (5 8 3 ?)

572 m

574 s 558 s

560 S

549 m

575 f

(577 s s ) (5 6 4 ss) 557 f

561 m

562 f f

559 s

550 m 542 s

(542 ?)

532 s 523 SS

B ib lio g ra p h y . The r e f e r e n c e s w i l l b e f o u n d l i s t e d i n o r d e r a t t h e e n d o f t h e v o lu m e . R e v ie w s : (2 6 ) P .A . P l a t t n e r , H e lv .C h im .A o ta , 1 941, 24, 283E . (4 5 ) H. A r n o ld , Die Chemie, 1943, 56, 7 . S .H . H a r p e r ,

Ann. R e p o r t s , 1 9 4 7 , 1 6 2 .

E a r l y Work: it Sem m ler, A t h e r i s c h e O le , L e i p z i g , 1 9 0 6 , I I I ,

260 f f .

E o r a c r i t i c a l r e v i e w o f w o rk up t o 1936 s e e : (6)

A.S* P f a u and P .A . P l a t t n e r , H e l v .C h im .A o t a , 1 9 3 6 , 1 £ , 858

S tru o ta re : (6)

A . S .P f a u and P . A . P l a t t n e r , H e lv .C h im .A o ta , 1 9 3 6 , 19^, 8 5 8 . Id e m , e t aL, i b i d . ,

(v e tiv o n e s):

(1 1 )

( t ) 1 9 3 9 , 22 , 6 4 0 ;

(1 0 ) 1 9 40, 2 3 , 768

1 9 4 0 , 2 3 , 8 97;

(1 2 ) 1 9 4 0 ,

2 3 , 9 0 7;

(13 )

19 41, 24 , 1 9 1 ;

(1 4 ) 1 9 4 1 ,

24, 1163;

(1 5)

1 94 2, 2 5 , 581 ( g u a j o l ) .

S y n th e sis: ( 6 , 7 ) A .S .P f a u a n d P . A . P l a t t n e r , H e l v .C h im .A o t a , 1 9 3 6 , 1 9 , 8 5 8 ; 1937 , 2 0 , 224 (fro m H a o k e l* s k e t o n e ) . ( 8 ) A . S .P f a u and P . A . P l a t t n e r , i b i d , 1 9 3 9 , 2 2 , 202 ( v e t i v a z u l ene:

d i a z o a c e t i o e s t e r m eth o d ).

P o r sab s e q u e n t m o d i f i c a t i o n s o f t h e d i a z o a c e t i o e s t e r m ethod s e e : (2 8 ) P l a t t n e r and R o n i g e r , i b i d , 1 943, 26 , 9 0 5 . ( 3 7 ,3 8 ) A r n o ld , B . , 1 947, 80* 1 2 3 , 1 7 2 . S y n th e se s o f 5 -m e th y la z u le n e by d ia z o a c e tio e s t e r m eth o d , Demjanow r i n g e x p a n s i o n , a n d c l o s u r e o f t h e 7membered r i n g : (2 0 ) P l a t t n e r and H o n i g e r , H e l v .C h im .A o t a , 1 9 4 2 , 2J5, 5 9 0 . (2 1 ) A r n o ld , B . , 1 943 , 7 6 , 7 7 7 . (2 2 ) Sorm e t a l , Co 1 1 . Czech*Chem.Comm., 1 9 4 7 , X I I , 81, 2 5 1 , 554 (2 3 ) P l a t t n e r , P f t r s t a n d S t u d e r , H e l v . C h i m . A o t a , 1 9 4 7 , 3 0 ,1 0 9 1 (2 4 ) P l a t t n e r , H e i l b r o n n e r and P l i r s t , i b i d , 1 1 0 0 . D ia z o m e th a n e r i n g e x p a n s i o n (4 6 ) C o a ts and Cook, J . C . S . , 1 9 4 2 , 5 5 9 . (2 3 ) P l a t t n e r ,

P t t r s t and S t u d e r , H e lv .C h im .A o ta , 1 9 4 7 , 3 0 ,1 0 9 1 .

S to b b e c o n d e n s a t i o n on o y o l o h e p t a n o n e * ( 4 0 ) P l a t t n e r and B d o h i , i b i d , 1 9 4 6 , 2 9 , 1 6 0 8 . (5 1 ) Cook, P h i l i p an d S o m e r v i l l e , J . C . S . ,

1948, 1 6 4 .

B io lo g ic a l p r o p e r tie s : C h a m a z u le n e :

(4 3 ) W .A rn o ld , A r o h . E x p t l . P a t h . P h a r m . , 192 7 ,

123, 129; (4 2 )

H e u b n e r and G r a b s , i b i d . ,

1933, 171, 329;

H e u b n er and A l b a t h , i b i d . , 1 9 3 9 , 1 9 2 , 3 83 ;

(4 1 ) W .A lb a th , i b i d . , (4 4 ) Ch.Pommer, i b i d . ,

1 9 3 9 , 1 9 3 , 619; 1942, 19 9 , 74.

A z u le n e and v e t i v a z u l e n e : (4-4) Ch.Pommer, i b i d . , 19 42 , 1 9 9 , 7 4 . S- and S e - g u a ^ a z u l e n e s : (4)

R u z ic k a a n d H a a g e n - S m it, H e lv .C h im .A o ta , 1 9 3 1 , 1 4 , 1122

S p e o tra ,: G l a s s i f i o a t io n i n t o s p e c t r u m g r o u p s : (2 6 )

P .A .P la ttn e r,

ib id .,

(28) P l a t t n e r a n d R o n ig e r ,

19 41, 2 4 , 283B; ib id .,

1 9 4 3 , 26^ 9 0 5;

(24 ) P l a t t n e r , H e i l b r o n n e r and P l i r s t ,

i b id # , 1947, 30, 1100.

X -ray: (5 5) M isc h a n d v a n d e r Wyk, C .A ., 1 9 3 8 , 32, 6523; i (83 ) G ttn th a rd , P l a t t n e r and B r a a d e n b e r g e r , B x p e r i e n t i a , 1948 4, 425. In fra-red : (8 4) G O nthard and P l a t t n e r , H e lv .C h im .A o ta , 1 9 4 9 , 32 , 2 8 4 . C hom atog r aphy t (2 8) P l a t t n e r and R o n i g e r , i b i d . , g iv e n .

1943, 26^ 905 and r e f s ,

P a rt I I

-

Ir o p o lo n es.

Summary. A s y n th e s is of 3 :4 -b e n z tro p o lo n e ( 3 :4 -b e n z c y c lo h e p ta 5 : ^ - t r i e n - l - o l - 2 - o n e XXX) i s d e s c r i b e d . 2 :3 -n en zsu b ero n e i s o x id is e d w ith selen iu m d io x id e t o th e g ^ d i k e t o n e XXIX, w h ic h i s t h e n d e h y d r o g e n a t e d w i t h p a l l a d i s e d c h a rc o a l in tric h lo ro b e n z e n e to b e n z tro p o lo n e . f u s i o n of t h i s w ith p o tash g iv e s c ^ -n a p h th o ic a c id , w h ile t h e p r e s e n c e o f t h e 7-m em bered r i n g i s c o n f i r m e d b y h y d r o g e n a ­ t i o n t o 3 : 4 - b e n z s u b e r a n - l : 2 - d i o l XXXII w h ic h i s o x i d i s e d b y h y p o b r o m it e t o t h e known ^ - 2- c a r b o x y p h e n y l b u t y r i o a c i d XXXIIi and b y p e r i o d i c a c i d t o y - 2 - fo rm y lp h e n y lb u t y r a l d e h y d e XXXIIIa* B e n z s u b e r a n d i o n e h a s a l s o "been b ro m L n a ie d t o a m i x t u r e o f a mo nob r omob enz sub e r a n d i o n e and a m o n o b ro m o b e n z tr o p o lo n e , and t h e l a t t e r h a s b e e n deb n o m in a te d t o b e n z t r o p o l o n e . P a lla d iu m d e h y d ro g e n a tio n o f su b e ran d io n e h a s n o t been s i m i l a r l y s u c c e s s f u l i n p ro d u c in g tro p o lo n e , b u t b r o m i n a t i o n h a s r e s u l t e d i n a bromo t r o p o l o n e , w h ic h h o w e v er h a s n o t b een d e b ro m in ate d .

OfL

[The name n t r o p o l o n e 11 was s u g g e s t e d b y Dewar00 f o r t h e o y c lo h e p t a t r i e n o l o n e s y s te m I , o e r t a i n u n iq u e f e a t u r e s . o f t h e d ik e t o n e I I I ,

and t h i s s t r u c t u r e h a s

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th e c o n ju g a tio n o f th e t h r e e d o u b le

b o n d s and t h e k e t o g ro u p t o fo rm a c l o s e d s y s te m , and t h e p o s s i b i l i t y o f r e s o n a n c e w i t h t h e a l t e r n a t i v e fo rm I I ,

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fro m w h ic h m ig h t b e e x p e c t e d a c o n s i d e r a b l e d e g r e e o f a c id ity ,

and Dewar s u g g e s t e d i n a d d i t i o n t h a t t h e c l o s e d

s y s te m I s h o u l d e x h i b i t q u a s i a r o m a t i c p r o p e r t i e s , w i t h s u p p r e s s i o n o f b o t h c a r b o n y l and d o u b l e b o n d r e a c t i v i t y . H is o r i g i n a l th e o r y a ls o in c lu d e d th e e x is te n c e o f a h y d r o g e n b o n d a s i n IV , w h ic h w ould i n c r e a s e t h e r e s o n a n c e e n e r g y and h e n c e t h e s t a b i l i t y , b u t o a l o u l a t i o n o f t h e 0 - 0 b o n d d i s t a n c e h a s shown t h a t i t may b e to o l o n g t o p e r m i t a n

o r d in a r y hy d ro g en bond S tip ita tio

87

a o id .

arhe o c c a s i o n f o r t h i s s p e c u l a t i o n was t h e d i s c o v e r y o f a m ould m e t a b o l i t e , s t i p i t a t i o

a c i d , w h ic h was v e r y f u l l y

d e s c r i b e d and c h a r a c t e r i s e d , t o g e t h e r w i t h some o f i t s 68

d e r i v a t i v e s , b y B i r k i n s h a w , Chambers and R a i s t r i c k i n 1942 ° . A lth o u g h t h i s s u b s t a n o e h a s t h e a p p a r e n t l y s im p le m o l e c u l a r fo rm u la

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sodium s a l t i s s t r o n g l y

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s o l u t i o n fro m w h ic h i t c a n b e r e g e n e r a t e d b y d i l u t i o n , s u g g e s t i n g t h e f o r m a t i o n o f an oxonium s a l t .

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o r k e t o g ro u p c o u l d b e d e t e c t e d w i t h a w id e v a r i e t y o f r e ­ a g e n ts.

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o a r b o x y l g r o u p , and t h e p r e s e n c e o f a p h e n o l i c h y d r o x y l a n d a s t r o n g l y a c i d i o - e n o l g r o u p w as a l s o d e m o n s t r a t e d .

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f i f t h ox y g en atom was u n a c c o u n te d f o r u n t i l i t was fo u n d t h a t on h y d r o g e n a t i o n a t e t r a h y d r o s t i p i t a t i o

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w h ic h was k e t o n i c and o n l y a mono b a s i c a o i d .

T h is

s u g g e s t e d t h e p r e s e n c e o f a c a r b o n y l g ro u p whose a c t i v i t y w as m asked i n some way i n t h e o r i g i n a l com pound.

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g e n e r a l s t a b i l i t y o f t h e m a t e r i a l s u g g e s t s an a r o m a ti c

compound - b ro m in e f o r ex am ple fo rm s a mono s u b s t i t u t i o n com­ pound w h ic h i s n o t r e a d i l y h y d r o l y s e d - an d a s t r i k i n g f a c t i s t h a t f u s i o n v /ith p o t a s h a t 300° g i v e s an e x c e l l e n t y i e l d o f t h e i s o m e r i c 5 -h y d r o x y i s o p h t h a l i o a c i d V.

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The o n l y f o r m u l a w b ic h B i r k i n s h a w , Chambers and R a i s t r i c k w e re a b l e t o s u g g e s t was 2 - f o r m y l - 3 : 5 - d i h y d r o x y b e n z o i c a c i d V I, b u t on s y n t h e s i s t h i s compound p r o v e d to b e d iffe re n t,

and i n f a c t g a v e t y p i c a l a ld e h y d e r e a c t i o n s .

Dewar now p r o p o s e d a h y d r o x y t r o p o l o n e s t r u c t u r e V I I . The se o o n d a c i d i c f u n c t i o n and t h e m asked c a r b o n y l r e a c t i v i t y a r e e x p l a i n e d b y t h e - e n o lo n e g r o u p i n g ,

and t h e s t a b i l i t y o f

th e su b s ta n c e by th e reso n an c e d e s c rib e d p r e v io u s ly . i s o - p h t h a l i o a c i d i s p ro d u c e d b y b e n z i l i c

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w o r k e r s h a v e a l s o shown t h a t two o t h e r f u n g u s p r o d u c t s - p u b e r u l i c and p u b e r u l o n i c

a c id s - have a tro p o lo n e s t r u c t u r e .

C o lc h ic in e . S h o r t l y a f t e r t h e s e s p e c u l a t i o n s , Dewar

89

p a t forw ard

t h e s u g g e s t i o n t h a t r i n g C o f o o l c h i o e i n e m ig h t a l s o h a v e a tro p o lo n e s t r u c t u r e ,

and t h a t c o l c h i c i n e an d i s o c o l c h i c i n e

w e re t h e two p o s s i b l e i s o m e r i c m e th y l e t h e r s .

T h is w o u ld

e x p la in th e a o i d i t y o f c o lc h ic e i n e , th e fo rm a tio n o f iso m erio d i b e n z e n e s u l p h o n a t e s , t h e i n t e n s e f e r r i c r e a c t i o n w h ic h i s n o t g iv e n b y c o l c h i c i n e , t h e i n t e n s e y e llo w c o lo u r o f i t s a lk a lin e so lu tio n s , c h lo rid e .

and t h e f o r m a t i o n o f a y e l l o w d i h y d r o -

The l a o k o f c a r b o n y l r e a c t i v i t y i s a l s o e x p l a i n e d

much m ore s a t i s f a c t o r i l y t h a n b y t h e o r i g i n a l h y d r o x y m e th y le n e 90 k e t o n e f o r m u l a o f W indaus , a s i s t h e s t a b i l i t y o f t h e d o a b l e b o n d s to w a r d s m a l e i c a n h y d r i d e and p e r b e n z o i o a c i d .

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W indaus

f u r t h e r e v id e n c e i s p ro v id e d by h y d ro g e n a tio n

91

, w hioh

p r o d u c e s a new h y d r o x y l f u n c t i o n , t h e p r o d u c t g i v i n g a c a r b o n y l compound w i t h p e r i o d i c a c i d ,

a s w o u ld b e e x p e c t e d fro m t h e o ( -

g l y c o l I Z , t h o u g h p r o b a b l y n o t fro m t h e

-g ly c o l IZ a.

f u r t h e r e v i d e n c e on t h i s p o i n t i s d i s c u s s e d l a t e r .

A lk a li 92 f u s i o n f o l l o w e d b y EMnO^ o x i d a t i o n g i v e s tjpfcrnellitio a o i d Z #

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