1). Synthesis of Dibenzcycloheptadienone. 2). Stereochemistry of Two Metabolic Diols

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1). Synthesis of Dibenzcycloheptadienone. 2). Stereochemistry of Two Metabolic Diols

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i).

s h t h b s is

Z) .

SfEKfiQCSEMIS TBY Off

op

dibkhzqyclqhjsptadikuqeb

A

TWO METABOLIC

T h e sis

su b m itted f o r th e d e g r e e o f D o cto r o f P h ilo so p h y a t th e U n iv e r s it y

of

Glasgow

W i ll i am I . W i l l i amson, B . Sc •

U n iv e r s it y o f G lasgow, Deo ember, 1 9 4 9 .

.

DIOLS -

ProQuest N um ber: 13870203

All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is d e p e n d e n t upon the quality of the copy subm itted. In the unlikely e v e n t that the a u thor did not send a c o m p le te m anuscript and there are missing pages, these will be noted. Also, if m aterial had to be rem oved, a n o te will ind ica te the deletion.

uest ProQuest 13870203 Published by ProQuest LLC(2019). C opyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying 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

Acknowl edgm ents. The au th or d e s i r e s to p la c e on r e c o r d h i s g r a t it u d e to P r o f e s s o r J.W. Cook and D r. J.D* Loudon f o r t h e i r gu id an ce and u n f a ilin g encouragem ent d u rin g th e p r o s e c u tio n o f t h e s e r e s e a r c h e s . He a ls o w ish e s to thank P r o fe s s o r L . Young f o r a g i f t o f l s 2 - d ih y d r o x y - ls 2 : 3 : 4 - t e t r a h y d r o n a p h th a le n e , Mr. J.M .L . Cameron and M iss R.H. Kennaway f o r m ic r o -a n a ly s e s , and th e D epartnent o f S c i e n t i f i c and I n d u s t r ia l R esearch f o r th e g r a n tin g o f a m aintenance a llo w a n ce c o v e r in g t h e p e r io d o f t h i s work.

The work c o n ta in e d in P art I form s p a r t o f a p ap er,

’C o lc h ic in e and R e la te d Compounds P a rt IX*

w hich h a s b een a c c e p te d f o r p u b lic a t io n by th e Chem ical S o c ie t y . 1949.

A b r i e f resume' o f p a r t o f th e work c o n ta in e d i n P a rt I I h as appeared in th e 2 6 th Annual Report o f th e B r i t i s h Empire Cancer Campaign (1 9 4 8 ), p . 2 4 9 .

G o u t

e n t a.

Page Summary Pari? I

P a rt I I

•••

•••

1

S y n t h e s is o f D ib e n z c y c lo h e p ta d ie n o n e I n tr o d u c tio n

...

...

4

D is c u s s io n

...

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15

E xp erim en tal

...

•••

Z9

B ib lio g r a p h y

...

...

52

S te r e o c h e m istr y o f Two M eta b o lic Dio I s I n tr o d u c tio n

...

...

54

D is c u s s io n

...

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63

E x p erim en ta l

...

•••

76

B ib lio g r a p h y

...

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107.

P a rt I .

S y n th e s is

of

Dib e n z c y o lo h e p t ad i en o n e .

Summary» P art I . An attem p t h a s b een made to s y n t h e s is e d e r i v a t i v e s o f d ib e n z o y o lo h e p ta d ie n e b y a p p r o p r ia te tr a n s fo r m a tio n o f th e two c a r b o x y lic a c id groups o f d ip h e n ic a c id ( I ;

R^CO^H)

COjM

(X)

(II)

(III)

By an a d a p ta tio n o f th e M cPadyen-Stevens p r o c e s s ^ ^

th e

aldehydo a c id ( I - R = OHO) h as been p rep ared and h en ce v i a th e d e r iv e d a c r y l ic ( I ; (I;

R = CH = CH.CQ^H) and p r o p io n ic

R s QHg.GH2 'CO^H) a c id s c y c l i s a t i o n to d ib e n z e y c lo -

h e p ta d ien o n e ( I I ) h as been d em o n stra ted .

The y i e l d s ,

h ow ever, are n o t good and attem p ted improvement b y desu.1 p h g r is a t io n o f th e p - t o l y l t h i o l e s t e r ( I ; (p ) ) a ffo r d e d o n ly th e a lc o h o l ( I ;

R 5 CO.S.CgH^.CHg

R = CH^OH).

An a l t e r n a t i v e m ethod, in v o lv in g th e s y n t h e s is o f (ill;

R - CO^H) and th e p r o je c te d ex p a n sio n o f th e c a r b o x y lic

t o th e p r o p io n ic a c id s i d e c h a in , f a i l e d b y r e a so n o f th e n n r e a c tiv e n a tu re o f th e e s t e r ( I I I ; f a c i l i t y w ith w hich ( I I I ; met h y lo l i d (IY)

R = GO^Me) and th e

R = CO^H) y ie ld e d th e d ip h e n y l-

OMe.

(IV )

(V)

(VI)

P a rt I I . As a c o n t r ib u t io n to know ledge o f th e s t e r e o ­ ch em ica l c o n f ig u r a t io n o f th e 1 : 2 - d ih y d r o x y - 1 : 2 - d ih y d ro n a p h th a len e and - a n th ra c en e, m e t a b o lit e s o f th e r e s p e c t i v e arom atic h yd rocarbons i s o l a t e d by Y o u n g ^

and by B o y l a n d ^

from r a t and r a b b it u r in e , th e c i s - and t r a n s - form s o f th e d i o l s (V) and (VI) have been s y n t h e s is e d .

In each

c a se th e c o n f ig u r a t io n h as b e e n a ss ig n e d on th e b a s i s o f th e g e n e r a l o r i t e r i a e s t a b lis h e d by C r ie g e e . In th e c a se o f (V) o p t i c a l r e s o l u t io n o f th e t r a n s ­ compound in t o i t s d and 1 - form s shows th a t th e form er i s i d e n t i c a l w ith th e d ih y d r id e o b ta in e d by Young through c a t a l y t i c h y d ro g e n a tio n o f th e n ap h th alen e m e t a b o lit e .

In

th e c a s e o f (VI) th e p h y s ic a l p r o p e r tie s o f th e s y n t h e t ic d l - t r a n s - compound i n d ic a t e i t s i d e n t i t y w ith th e d ih y d r id e o f th e o p tim a lly i n a c t i v e an th racen e m e ta b o lite d e s c r ib e d by B o y la n d .

In c o n ju n c tio n t h e r e f o r e w ith th e f a c t th a t th e

9 : 1 0 - d ih y d r o x y -9 : 1 0 -d ih y d ro p h en a n th ren e, th e c o r r esp o n d in g m e t a b o lit e o f phenanthr ene from r a t s ,

i s s a id to b e o p t i c a l l y

a ctiv e^ ® 4^ and m ast a c c o r d in g ly be th e tr a n s iso m e r , i t app ears th a t th e m e ta b o lic p r o c e s s o f h y d r o x y la tio n le a d s t o th e t r a n s - and n o t to th e c i s - c o n f ig u r a t io n .

P art I »

I n t r o d u c t io n . The w id esp rea d i n t e r e s t i n c o l c h i c i n e , th e a lk a lo id o f th e meadow s a f f r o n (G olchicum autum nale L .) d e r iv e s , p r im a r ily , from i t s b i o l o g i c a l p r o p e r t i e s .

The m ost p ro ­

nounced o f t h e s e i s i t s a n t im it o t ic a c t io n w hich makes i t an in v a lu a b le r ea g e n t f o r p rod u cin g p o ly p lo id v a r i e t i e s o f p la n ts .

I t h a s a ls o b een found to i n h i b i t tumour

grow th, a lth o u g h i t s u se in t h i s l a t t e r r e s p e c t i s lim i t e d by i t s v e r y h ig h t o x i c i t y . The ch em ical c o n s t i t u t i o n o f c o lc h i c i n e i s s t i l l unknown a lth ou gh r e c e n t work i n t h e s e la b o r a t o r i e s h as added c o n s id e r a b ly to our know ledge i n t h i s f i e l d . MeO' 1^0 m

OMe

% /P (II)

(I)

(III)

The form u la ( I ) f o r c o lc h i c i n e proposed i n 1924 by Windaus^*^ h a s been shown i n r e c e n t y e a r s t o b e u n s a t i s ­ fa cto r y .

I t i s conceded t h a t c o lc h i c i n e c o n ta in s a

t r i c y c l i c system and t h a t r in g A h as th e s t r u c t u r e a s s ig n e d to i t by W indaus.

The six-m em bered r in g s t r u c t u r e s o f i3

and C how ever h ave b een s u b j e c t t o a d v erse c r i t i c i s m

as

b e in g in c o m p a tib le w ith th e known c h em ica l p r o p e r t ie s o f c o lc h ic in e .

In th e p r e s e n t d i s c u s s i o n we w i l l c o n s id e r

o n ly th e n a tu r e o f r in g B .

T h is problem h a s b een p a r t l y

e lu c id a t e d by a c o n s id e r a t io n o f th e d e g r a d a tio n p rod u ct o f c o l c h i c i n e , d e a m in o c o lc h in o l m eth yl e th e r , to w hich Windaus a ss ig n e d th e s tr u c tu r e ( I I ) . C o lc h ic in e c o n t a in s one m eth oxyl group w hich i s r e a d ily h y d r o ly s e d , th e produ ct o f h y d r o ly s is b e in g c o l c h ic e in e .

Treatm ent o f c o lc h i c e i n e w ith io d in e in th e

p r e sen ce o f a l k a l i y i e l d s U - a c e t y lio d o c o l c h i n o l s CEIH23°6H

*

1

>

+

(CH0)

D e h a lo g e n a tio n fo llo w e d by d eam in ation o f t h i s produ ct y i e l d s d e a m in o c o lc h in o l m eth yl e th e r and th e is o m e r ic is o -d e a m in o c o lc h in o l m eth yl e th e r .

When dem ethyl a t ed by

trea tm en t w ith h y d r io d ic a c id and th e n d i s t i l l e d w ith z in c d u st, d e a m in o c o lc h in o l m eth yl e th e r was c o n v e r te d to 9 m eth ylphenan thren e and on t h i s b a s i s Windaus assumed i t . a. w a s^ te tra m e th o x y la ted m eth y lp h en a n th ren e. Windaus d ecid ed i t was a 9 -m eth yl phenanthr ene ( I I ) r a th e r th a n a 1 0 -m eth y l d e r iv a t i v e on th e f o llo w in g e v id e n c e .

G o lc h ic in e i s

o x id is e d by chromic a c id to a k e to n e , o x y c o lc h ic in e , U22S 23°7^

^ ^ y l e n e group im p lie d by t h i s o x id a tio n

can be p rovid ed o n ly in r in g B.

I f such a m eth ylen e group

i s p r e s e n t i n r in g B th e n th e two s u b s t it u e n t s p r e s e n t in t h i s r in g , v i z . -uHg and -BHGOCHg, mast be a tta c h e d to th e same carb on atom .

How o o lc h in o l m eth y l e th e r ( I I I )

was o x id is e d by chrom ic aofid to 4 -m eth o x y p h th a lim id e, s u g g e s t in g t h a t th e n it r o g e n atom i s se p a r a te d from r in g G by a s i n g l e carb on atom .

I t f o llo w s t h e r e f o r e th a t th e

-MCOCHg group, and h en ce a ls o th e -CHg group, i s a tta c h e d to th e 9 - p o s i t i o n i n r in g B .

A nother p ie c e o f e v id e n c e

brought forw ard by Windaus i n fa v o u r o f th e six-m em bered n a tu re o f r in g B was th e o x id a t io n o f I -b e n z o y l t r im e th y l o o lc h in ic a c id .

f r im e t h y lc o lc h in ic a c id i s formed by

d e a c e t y la t io n o f c o lc h i c e i n e , and trea tm en t o f i t s H -b en zoyl d e r iv a t iv e w ith c o ld a l k a l i n e permanganate le a d s to th e o x id a t io n o f r in g G w ith fo rm a tio n o f H -b e n z o y lc o lc h id e and I - b e n z o y lc o lc h in ic a c id a n h y d r id e .

(IT )

(V)

(Y I)

(Y II)

fh e s t r u c t u r e s p o s tu la t e d by Windaus f o r t h e s e o x id a t io n p r o d u c ts, (IV ) and (V) r e s p e c t i v e l y , were con ­ s i s t e n t w ith ;

(a ) th e read y d ea m in a tio n o f th e form er,

which w ould be r e p r e se n te d as ( I V )

> (Y I) on t h i s

f o r m u la tio n , and (b ) th e fo r m a tio n o f a l a c t o n e , su p p o se d ly p e r i- l ih k e d as in (V I I ) , by tre a tm en t o f th e anh ydride w ith h y d r io d ic a c id . I h a t W indaus's fo r m u la tio n o f d e a m in o c o lc h in o l m eth y l e th e r and o f c o lc h i n o l m eth yl e th e r as ( I I ) and ( i l l ) r e s p e c t i v e l y was n ot i n accord an ce w ith th e p r o p e r t ie s o f th e s e compounds was f i r s t p o in te d out by Gohen, Gook and E oe^ •

Thus ( I I I ) i s a d e r iv a t iv e o f 9 -a m in o -9 slO -d i-

hydrophenanthrene w hich sh o u ld r e a d il y e lim in a t e ammonia and p a ss in t o th e w h o lly arom atic s t a t e .

G o lc h in o l m eth yl

e th e r how ever d is p la y s no such r e a d in e s s to e lim in a t e ammonia.

M oreover, when c o lc h i n o l m etb y l e th e r i s co n ­

v e r te d to a c a r b in o l by trea tm en t w ith n it r o u s a c id , th e o a r b in o l o b ta in e d i s much more r e s i s t a n t to th e e lim in a t io n o f w a ter than w ould be th e c a s e w ith th e t e r t i a r y c a r b in o l th a t would a r is e from form u la ( I I I ) .

fh e s e i n d ic a t io n s

th a t th e form u la ( I I ) was in c o r r e c t were co n firm ed b y th e s y n t h e s is o f b oth compounds c o rresp o n d in g to t h i s form u la, n e it h e r o f w hich was i d e n t i c a l w ith d e a m in o c o lc h in o l m eth yl ether^. An a l t e r n a t i v e s t r u c t u r e (V II) f o r d e a m in o c o lc h in o l m eth y l e th e r was p roposed by B a rto n , Cook and L o n d o n ^ .

8.

10 US

(V I II)

(V II)

(IX)

On th e b a s i s o f t h i s d ib e n z c y c lo h e p ta tr ie n e s t r u c t u r e a l l th e f a c t s e x p la in e d by Windaus by h i s s i x membered r in g B s t r u c t u r e can be e q u a lly w e l l e x p la in e d . Thus th e fo rm a tio n o f 9-m eth ylp h en an th ren e from deam inoo o lc h in o l m eth yl e th e r by d e m e th y la tio n fo llo w e d by z in c d u st d i s t i l l a t i o n means th a t th e d r a s t ic c o n d itio n s have b rough t about a c o n t r a c t io n o f th e seven-m em bered r in g . That th e d ib e n z c y c lo h e p ta tr ie n e frameworh d o es rea rra n g e i t s e l f under t h e s e c o n d it io n s h a s b een proved by th e obt'3*S s e r v a t io n th a t 3 : 4 t 5 t 6 - d i b e n z - A - o y c lo h e p t a tr ie n e a ff o r d s 9-m eth y l phenanthrene when h e a te d w ith h y d r io d io a o id and th en d i s t i l l e d w ith z i n c .

The o x id a tio n o f c o l ­

c h in o l m eth yl e th e r to 4-m eth oxyp h th alim id e and o f c o l ­ c h ic in e to o x y c o lc h ic in e are s t i l l u n d ersta n d a b le i f r in g B i s seven-m em bered and fu rth erm ore th e p r e se n c e o f s u c c in ic a c id among th e o x id a t io n p ro d u cts o f c o l c h i c i n e and i t s d e r iv a t i v e s , w hich was o b served by W indaus, now becomes u n d ersta n d a b le a l s o .

The fo rm a tio n o f N -b en zo y l c o lc h id e

amo(,

U - b e n z o y lc o lc h in ic a c id an h ydride d o es n o t i n v a l i d a t e t h i s new p r o p o s a l s in c e th e stru.ctu.re o f th e s e o x id a t io n p ro ­ d u c ts h a s n ot b een r ig o r o u s ly proved and i t may be t h a t th e y a ls o c o n ta in a seven-m em bered r in g .

A more p o s i t i v e

p r o o f o f th e c o r r e c t n e s s o f th e p o s t u la t e d seven-m em bered r in g s t r u c t u r e i s p ro v id ed by th e f o llo w in g s e r i e s o f r e (4 ) aci

(Z)

(Z I)

(Z II)

D e a m in o co lch in o l m eth yl e th e r (V II) and th e iso m e r ic i s o ­ deamino c o lc h in o l m eth y l e th e r (V III) are b oth r e a d il y h y d ro g en ated w ith p r o d u c tio n o f th e same d a h y d r id e .

She

e t h y le n ic lin k a g e th u s d i s c l o s e d i n d e a m ih o c o lc h in o l m eth yl e th e r i s s u b je c te d to s te p w is e o x id a t io n , f i r s t w ith osmium t e t r o x i d e to a g l y c o l (Z) th e n by c le a v a g e w ith le a d t e t r a ­ a c e t a t e to a d i-a ld e h y d e (Z I) w hich c y c l i s e s to th e 10ph en anth rald eh yde ( Z I I ) .

fhe s t r u c t u r e o f t h i s ald eh yd e

i s proved b y i t s o x id a t io n to th e c a r b o x y lic a c id and com­ p a r is o n o f th e l a t t e r w ith a s y n t h e t ic specim en o f 2 s 3 s 4 j 7 tetr a m e th o x y p h e n a n th r e n e -1 0 -c a r b o x y lic a c id .

A s im ila r

s e r i e s o f r e a c t io n s s t a r t i n g from is o -d e a m in o c o lc h in o l m eth yl e th e r g iv e s r i s e to th e co rresp o n d in g 9 -p h en an th r-

a ld e h y d e .

S in c e Hofmann d e g r a d a tio n d oes n ot g e n e r a lly (5 ) in v o lv e any change i n th e carbon s k e le t o n , i t may be assumed t h a t c o lc h i n o l m eth y l e th e r a ls o c o n ta in s a s e v e n membered r in g as shown i n ( I X ) . W hile i t

i s not y e t c e r t a i n t h a t c o l c h i c i n e i t s e l f

c o n ta in s a seven-m em bered r in g , th e p r e se n c e o f such a r in g i n c e r t a i n o f i t s d e g r a d a tio n p r o d u cts makes i t o b v io u s ly d e s ir a b le to e v o lv e a method o f s y n t h e s is in g s im ila r d ib e n z e y c lo h e p ta tr ie n e s -

Such a method would need to be

a p p lic a b le to th e s y n t h e s is o f d ib e n z c y c lo h e p ta tr ie n e s u n sy m m etrica lly s u b s t it u t e d i n th e arom atic n u c l e i .

Most

o f th e s y n th e s e s h it h e r t o a c h ie v e d f a i l to f u l f i l t h i s l a t t e r c o n d it io n . The f i r s t s u c c e s s f u l s y n t h e s is o f a d ib e n z c y c lo f6) h e p ta d ie n e was due to Kenner ' who o b ta in e d th e k e to n e (X III) from 2 : 2 ’ - d i t o l y l - w •

(X III)

-d ic a r b o x y lo n itr ile .

(XV)

C on tin u in g t h i s work on th e c y c l i s a t i o n o f d e r iv a t i v e s o f (7)

2 :2 f - d i t o l y l ,

Kenner

f

o b ta in e d from ^

-d ib r o m o -2 s2 f -

d i t o l y l by c o n d e n sa tio n w ith m alonic e s t e r , d i e t h y l - 3 j 5 d ib e n z -

i-.s

- c y c lo h e p ta d ie n e - 1 : l- d ic a r b o x y la t e w hich on

h y d r o ly s is and d e c a r b o x y la tio n y i e l d e d th e a c id ( X I V ) (B = COgH) .

The amine (XIV, B s M g ) was o b ta in e d from

t h i s a c id by th e C u r tin s r e a c t io n and dry d i s t i l l a t i o n o f i t s h y d r o c h lo r id e a ffo r d e d 3 :5 -d ib e n z -A ' 3 3- c y c lo h e p t a t r ie n e (XV) •

A s im ila r s y n t h e s is o f a d ib e n z c y c lo h e p ta t r ie n e

r eco rd ed by W eitzenbdck

( 8)

i s th e c y c l i s a t i o n o f b ip h e n y l-

e n e - 2 : 2 ’ - d ia c e ta ld e h y d e t e t r a m e t h y la c e t a l to th e ald eh yd e (XVI) .

Somewhat s im ila r i s th e fo rm a tio n o f th e k e to n e

(XVII) by h e a t in g 2 -b r o m o -5 -n itr o -a c e to p h e n o n e w ith copper where in tr a m o le c u la r c o n d e n sa tio n o f th e in te r m e d ia r y d ip h e n y l (X V III) o ccu rs

The c o n d e n sa tio n o f d ip h e n ic anhydride w ith cL - p i c o l i n e and q u in a ld in e g iv e s r i s e to d ib e n z c y c lo h e p ta d ie n e s o f th e , ,( 10,11) ty p e (XIX) . Hone o f th e s e m ethods, how ever, gave prom ise o f b e in g a p p lic a b le to th e s y n t h e s is o f unsymm e t r i c a l ly s u b s t it u t e d d ib e n z o y c lo h e p ta tr ie n e s , b u t t h i s c o n d it io n i s f u l f i l l e d i n a r e c e n t l y d e s c r ib e d s y n t h e s i s ^ 2 ^ . Here th e s t a r t i n g m a te r ia l i s a 9 - or 1 0 -m eth y l phenanthrene which i s o x id is e d w ith osmium t e t r o x i d e .

C leavage o f th e

d i o l so form ed w ith le a d t e t r a - a c e t a t e a f fo r d s an ald eh yd e w hich c y c l i s e s to a d ib e n z c y c lo h e p t a t r ie n e .

I n t h i s way

9 s l 2 i l 3 i l 4 - t e t r a m e t h o x y - 3 s 4 ?5 : 6 - d ih e n z c y c lo h e p t a - ls 3 i5 t r ie n e - 7 - o n e (XXI) h a s been s y n t h e s is e d from 2 * 3 i4 * 7 tetram eth oxy-9-m eth ylp h en an th ren Q (XX) as i l l u s t r a t e d i n th e f o llo w in g schem es-

(XX)

(XXI)

T his s y n t h e t ic p rod u ct h as been found to be i d e n t i o a l w ith an o x id a tio n p rodu ct o f d e a m in o c o lc h in o l m eth y l e t h e r . s y n t h e s is d e s c r ib e d i n a r e c e n t p u b lic a t io n by Rapoport (13) and W illia m s w hich may a ls o prove a d a p ta b le to th e s y n t h e s is o f u n sy m m etrica lly s u b s t it u t e d d e r i v a t i v e s , and w hich i n p a r t d u p lic a t e s th e work to be d e so r ib e d i n t h i s t h e s i s , i s shown i n o u t l i n e b e lo w .

A

(mi) CM CMO CM

(mu)

(2X7)

The oyano a o id (XXII) i s o b ta in e d by Beckmann r e a r r a n g e ­ ment o f phenanthrenequinonem onoxim e and c o n v e rted to th e aldehyd e ( m i l )

by Rosenmund r e d u o tio n o f i t s o h lo r id Q .

C o n d en sa tion o f t h i s aldehyde w ith m alon ic a o id a ffo r d e d th e oyano cinnam ic a o id (XXIV) w hich was c o n v e r te d to th e sa tu r a te d d ib a s ic a c id (XXVI) b y e it h e r o f th e two r o u te s in d ic a t e d .

The a c id (XXVI) was c y c l i s e d to th e k eto n e

(XXX) by two m ethods:

a) by p y r o ly s is o f th e thorium s a l t

and b) by th e Dieckmann method fo llo w e d by s a p o n i f i c a t i o n and d e c a r b o x y la tio n o f th e in te r m e d ia te

(3 -k e to e s t e r ,

i n a l t e r n a t i v e , and more e f f i c i e n t method f o r c o n v e r tin g

14.

tli© oyano cin nam ic a c id (XXIY) t o th e c y c lo h e p ta d ie n e i s a ls o o u t l i n e d .

T h is in v o lv e s fo rm a tio n o f th e d i n i t r i l e

(XXVIII) whioh i s c y c l i s e d by t h e Z ie g le r p roced u re to th e o y a n o -im in e (XXIX) .

H y d r o ly s is o f t h i s c y a n o -im in e

a f f o r d s th e k e to n e (XXX) i n e x c e l l e n t y i e l d . In th e f o llo w in g s e c t i o n th e p r e s e n t a u th o r ! s a ttem p ts to fin d an a l t e r n a t i v e approach to th e d e S ir e d s y n t h e s is are d e s c r ib e d .

rI

■"' ■o fci: o;v O-f a 0 o r b o n a t cm :V;£



r e l;r!1 4 p t'h--

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1}g t m

-

t ':

"-V'

P i so a s s i o n .

In th e p r e s e n t work tfto m ethods o f approach to th e s y n t h e s is o f d ib e n z o y c lo h e p ta tr ie n e d e r iv a t i v e s were con ­ sid e r e d sc—

(A)

(B)

A d ip h en y l n u c le u s i s p r e se n t i n th e s t a r t i n g m a te r ia l in each o a s e .

In (A) th e s t a r t in g m a te r ia l i s d ip h e n ic a c id

o r i t s d e r iv a t iv e s and an attem p t i s made to com p lete th e r in g hy th e in t r o d u c t io n o f a carbon atom as s k e tc h e d .

In

(B) an attem pt i s made to b r id g e th e two phenyl r e s id u e s by a th r e e carbon atom c h a in a tta c h e d to one o f them, i . e . , th e s t a r t in g m a te r ia l i n t h i s c a s e i s a p h en yl hydro cinnam ic a c id .

A p a r t ic u la r approach b y th e f i r s t r o u te w ould be

f o r exam ple, co

2 he i n i t i a l problem i s to make th e h a l f ald eh yd e

and to

th a t end th e procedure f i r s t c o n sid e r e d was an a d a p ta tio n

o f t h a t used f o r th e p r e p a r a tio n o f a ld e h y d e s from mono(14 j

b a s ic a c id s by MoEadyen and S te v e n s' B.002H ----- »

, v iz :-

l a 2003 R.OO.IH.HH.SOgPB -------- ^ B.OHO ♦ PhS02Ba ♦

S in c e i n th e p r e s e n t c a s e t h i s w ould need to be a p p lie d to o n ly one o f the c a r b o x y l groups o f d ip h e n ic a c id , i t had f i r s t to b e a s c e r ta in e d th a t the d e s ir e d m onophenylsulphonh y d ra z id e c o u ld b e made a v a i l a b l e .

Two m ethods o f o b t a in ­

in g th e m onophenylsulphonhydrazide o f d ip h e n ic anhydride were s u c c e s s f u l l y e la b o r a te d ; (a )

b y trea tm en t o f th e anhydride w ith h y d ra z in e h y d ra te to

form th e m onohydrazide, fo llo w e d by r e a c t io n w ith b en zen esu lp h o n y l c h lo r id e , (b)

and

d i r e c t l y , by t r e a t i n g th e anhydride w ith b en zen esu lp h o n -

h y d r a z id e .

The l a t t e r ,

though g iv in g a produ ct con tam in ated

w ith a sm a ll amount o f an iso m e r ic compound, had th e ad­ va n ta g e o f few er s t a g e s and b e t t e r y i e l d based on th e an­ h y d r id e .

I t was a ls o a p p lic a b le to p h th a lic anhydride

w hich, through out t h i s s e r i e s o f e x p erim en ts, was f r e q u e n t ly u sed as a g u id e to th e p rob ab le b eh a v io u r o f d ip h e n ic an­ h y d r id e . Attem pted d e c o m p o sitio n o f th e p h en ylsu lp h on h y d ra zid e o f p h t h a lic a c id f a i l e d to produce any a ld e h y d e . On th e o th e r hand, i n i t i a l a ttem p ts in th e d ip h e n ic a c id

s e r i e s showed th a t i n t h i s c a s e th e ald eh yd e c o a id be ob­ t a in e d .

The y i e l d however was poor and th e a s a a l se p a r a ­

t i o n o f th e n e a t r a l aldehyde p ro d a ct from b o th unchanged sodium c a r b o x y la te and th e sodium sulphibnate produced i s ren dered in a p p lic a b le by t h e p r e sen ce o f th e r e s i d u a l ca rb o x y l group i n th e h a l f aldehyd e (XXXI) .

crto

M o d ific a tio n s o f th e r e a c t io n c o n d it io n s , w ith r e s p e c t to b o th tem perature and d u r a tio n o f th e r e a c t io n f a i l e d to e f f e c t a s a t i s f a c t o r y in c r e a s e in t h e y i e l d o f a ld eh y d e, a c o n s id e r a b le p e r ce n ta g e o f th e p h en ylsu lp h orih yd razid e r e s i s t i n g d e c o m p o sitio n .

fu r th e r a ttem p ts were th e n made

a lo n g th e l i n e o f more e f f i c i e n t s e p a r a tio n o f th e ald eh yd e from t h e unchanged su lp h on h yd razid e and th e sodium s u l p h in a te produ ced.

I t was c o n sid er ed th a t a s e p a r a tio n

c o u ld p o s s ib ly be e f f e c t e d by form ing an a c e to x y -la c to n e (XXXII) o f th e aldehydo a c id (XXXI) w hich c o u ld be r e a d i l y se p a r a te d from th e p h en yl su lp h on h yd razid e and t h e sodium s u lp h in a te because o f i t s

a lk a lin e i n s o l u b i l i t y ,

and from

w hich th e a ld e h y d o -a c id c o u ld be r e a d il y r e g e n e r a te d .

It

was a s c e r t a in e d th a t th e a ld e h y d o -a c id d id in d eed form an a lk a lin e i n s o l u b l e a c e t o x y - la c t o n e , c o n v e n ie n tly p rep ared by trea tm en t o f th e a ld e h y d o -a c id w ith a c e t i c anhydride i n p re sen ce o f a l i t t l e c o n c e n tr a te d s u lp h u r ic a c id , and th a t th e a ld e h y d o -a c id was r e g e n e r a te d b y h y d r o l y s is .

T h is ,

t h e r e f o r e , w ould be a s a t i s f a c t o r y p r o c e ss i f th e p h en y lsu lp h o n h y d razid e were unchanged by th e above tr e a tm e n t w ith a c e t ic a n h y d rid e.

U n fo r tu n a te ly however under th e s e con ­

d i t i o n s th e p h en ylsu lp h orih yd razid e a ls o y ie ld e d an a l k a l i in s o lu b le compound o f e m p ir ic a l form ula G22% 605% s a2li p o s s e s s in g th e r e f o r e e i t h e r s t r u c tu r e (XXXIII) or (XXXTV)

(XXXIII)

(XXXIV)

The p h en y lsu lp h o n h y d ra zid e was th e n t r e a t e d w ith a o e t ie anhydride in th e p r e se n c e o f p y r id in e in t h e hope th a t th e p y r id in e would p r e se r v e th e c a r b o x y l group i n t a c t and le a d to th e fo rm a tio n o f an a l k a l i s o lu b le p r o d u c t.

The com­

pound o b ta in ed by t h i s method however was a g a in i n s o lu b l e i n a l k a l i and was in f a c t i d e n t i c a l w ith th e p r e v io u s com­ pound.

The method o f s e p a r a tio n f i n a l l y adopted was b a sed

on th e o b s e r v a tio n th a t th e p h en y lsu lp h o n h y d ra zid e, b u t not

th e a ld e h y d o -a c id , was p r e o ip it a t e d from a l k a l i n e s o l u t i o n by su lp h u r d i o x i d e .

A c c o r d in g ly th e d e s ir e d s e p a r a tio n was

e f f e c t e d b y t r e a t i n g th e a lk a lin e s o l u t i o n from th e r e a c t io n w ith su lp h u r d io x id e t i l l a l l unchanged p h en y lsu lp h o n h y d ra z id e was p r e o ip it a t e d and th e n o b ta in in g th e aldehyd e f r e e from b y -p r o d u c ts by a c i d i f i c a t i o n w ith m in e r a l a c id .

By t h i s

m ethod a y i e l d o f 34$ o f th e a ld e h y d e, b a sed on th e p h e n y lsu lp h o n h y d ra z id e , was a t t a in e d . At t h i s s t a g e in th e s y n t h e s is b e t t e r y i e l d s th a n t h e s e r e a l i s e d i n th e above p r o c e s s are im p e r a tiv e .

A ccord­

i n g l y o th e r m ethods f o r th e c o n v e r s io n o f c a r b o x y l to aldehydo groups were c o n s id e r e d . The method d e sc r ib e d by (1 5 ) Wolfrom and K arabinos f o r th e s y n t h e s is o f a ld eh y d es from t h i o l e s t e r s by d e s u lp h u r is a t io n w ith Raney n i c k e l i n a lc o h o l appeared to be th e most p r o m isin g .

I t was n e c e s s a r y

to a s c e r t a in th a t a h a l f t h i o l e s t e r c o u ld be o b ta in e d from d ip h e n ic a c id and i t was a ls o d e s ir e d to d eterm in e i f th e method were a p p lic a b le t o t h i o l s o th e r than e t h y l m ercaptan w hich had b een employed b y Wolfrom and K a rab in os.

In t h i s

c a s e th e t h i o l u sed was th io -jD -c r e so l o f which a su p p ly was a v a ila b le .

As b e f o r e , th e b eh a v io u r o f p h th a lic anhydride

was f i r s t s t u d ie d . The d i t h i o l e s t e r s o f p h t h a lic a c id have b een d e sc r ib e d by C hakravarti and 3aha^"^ who o b ta in e d them by

th e c o n d e n sa tio n o f p h t h a lic anhydride w ith th e t h i o l a t 140°0 and w ith phosphorus p e n to x id e as c o n d en sin g a g e n t. They r e p o r te d th a t no c o n d e n sa tio n c o u ld he e f f e c t e d by em ploying su lp h u r ic a c id , dry h y d r o c h lo r ic a c id , anhydrous z in c c h lo r id e or anhydrous z in c c h lo r id e and h y d r o o h lo r io a c id a s co n d en sin g a g e n t s .

The mono t h i o l e s t e r o f p h th a lic

a c id w hich was r e q u ir e d i s not d e s c r ib e d i n th e l i t e r a t u r e . The c o n d e n sa tio n f ^ f f \ 4 . hs--carbomethoxy b e n z o y l c h lo r id e .

.W o r d in g to H. Meyer

(18)

t h i s a c id c h lo r id e i s

o b ta in e d as a c o l o u r l e s s o i l w hich d o es n o t s o l i d i f y on c o o lin g to -1 8 ° 0 , by th e r e a c t io n o f monomethyl p h th a la te w ith t h io n y l c h l o r i d e .

The c h lo r id e i s decomposed b y

h e a tin g on a w ater b ath or more s lo w ly on sta n d in g a t room tem perature a c co r d in g to th e e q u a tio n s »

CO/

CO Cl.

o

+ cri3 ci.

The o i l o b ta in e d by t r e a t i n g monomethyl p h th a la te w ith t h io n y l c h lo r id e was f r e e d from t h io n y l c h lo r id e and t r e a t e d w ith t h io - j o - c r e s o l and p y r id in e a t 0°G.

A c r y s ta llin e s o lid

was o b ta in e d from th e r e a c t io n which was th e d e s ir e d j o - t o ly l £ -c a r b o m e th o x y th io lb e n z o a te ( XXXVI ) . I t had meantime b e e n found th a t th e b eh aviou r o f d ip h e n ic anhydride tow ards t h i o - £ - c r e s o l was q u ite d i f f e r e n t from t h a t o f p h th a lic a n h y d rid e.

By a llo w in g th e r e a g e n ts

to sta n d o v e r n ig h t i n p y r id in e a 40$ y i e l d o f th e h a l f t h i o l e s t e r (XXXV) was o b ta in e d . cos cos i^ V c o ^ . (XXXV)

CH3

c o 2h.

( XXXVI )

The r e a c t io n i n h o t p y r id in e was th en s t u d ie d i n an attem p t to im prove on t h i s y i e l d .

The optimum c o n d itio n s were found

to b e h e a tin g at 70°C f o r n in e t y m in u te s .

Under t b e s e c o n ­

d i t i o n s a y i e l d o f 70$ o f th e h a l f t h i o l e s t e r was a t t a in e d . The d e s u lp h u r is a tio n o f t h e s e t h i o l e s t e r s w ith Raney n i c k e l was c a r r ie d o u t under th e c o n d it io n s d e sc r ib e d by Wolfrom and E a r a b in o s.

The p rod u ct o b ta in e d from ]>-

to ly l-o -c a r b o m e th o x y th io lb e n z o a te (XXXVI) was p h th a lid e (XXXVII), i . e . ,

th e t h i o l e s t e r g rou p in g was red uced to th e

a lc o h o l and th e m eth yl e s t e r h y d r o ly s e d .

L a c t o n is a tio n

betw een th e a lc o h o lic and c a r b o x y l groups produced w ould th e n g iv e r i s e to p h t h a lid e . c%

ah

£1

(XUXLI)

(XHXVIII)

The j a - t h i o t o l y l hydrogen d ip h e n a te (XXXV) t r e a t e d i n th e same way gave r i s e to th e a lc o h o l, 2 -h yd roxym eth yld ip h e n y l- 2 1- c a r b o x y lic a c id (XXXVIII) .

In t h i s c a s e

l a c t o n i s a t i o n d id n ot occur during th e r e a c t io n .

In n e it h e r

c a s e c o u ld more th a n 20 $ o f th e m a t e r ia l be a cco u n ted f o r in th e p r o d u c ts .

S im ila r r e s u l t s were o b ta in e d w ith £ - t o l y l

th io lb e n z o a t e (XXXIX), i . e . ,

low y i e l d o f th e a lc o h o l w ith

no t r a c e o f any a ld eh y d e, and t h i s method was th e r e f o r e ab andoned.

The r © s a l t s o b ta in e d her© ar© i n accordan ce w ith (19) (20) t h o s e o f P r e lo g , Prank, Pant a and T a r b e ll and ( 21) McMillan , a l l o f whom have r e p o r t e d t h e f o r m a tio n o f prim ary a l c o h o l s hy Raney n i c k e l d e s u lx )h u r is a tio n o f t h i o l esters.

The l a s t named aath or h as a l s o r e p o r te d t h e forma­

t i o n o f hydrocarbons i n t h i s r e a c t i o n by removal o f t h e e n t i r e t h i o l e s t e r grou p .

More r e c e n t l y

( 22)

' i t h a s b een

r e p o r te d t h a t , w h ile f r e s h l y prepared Raney n i c k e l l e a d s to t h e f o r m a tio n o f a l c o h o l s , a ld eh y d es can be o b ta in e d by de­ a c t i v a t i n g th e o a t a l y s t . An i n v e s t i g a t i o n o f anoth er p o s s i b l e r o u t e to th e

h a l f aldehyde o f d ip h e n ic a c id was th e n u n d ertak en . P h is (23) was based on a s y n t h e s i s o f p h th a la ld e h y d ic a c id bu t i n t h e c a s e o f d ip h e n ic a c id , r e d u c t io n o f diphenim ide y i e l d e d diphenamic a c id i n s t e a d o f th e d e s i r e d i n t e r m e d ia t e , d ip h e m d e , and th e method was t h e r e f o r e i n a p p l i c a b l e . With th e h a l f aldehyde o f d ip h e n ic a c id o b ta in e d v i a the p h en ylsu lp h on h yd razid e th e n e x t s t a g e i n th e s y n t h e s i s was attem p ted .

This in v o lv e d , as a lr e a d y e x p la in e d , th e

i n t r o d u c t i o n o f a carbon atom to form a l i n k betw een t h e aldehydo and c a rb o x y l g roups-

She method adopted t o a c h ie v e

t h i s was a c o n d e n sa tio n o f t h e aldehyde w ith m alonic a c i d . On paper t h e r e are a v a r i e t y o f p o s s i b l e p r o d u cts from t h i s r ea c tio n ,

e .g .

C H U o t H )2

crtj. coitf

i

O

(XLII)

(XLI)

( XL)

cHi- Co^H

c Cco, H),

cri.co2fi

vy c r i 2.crti. cOiH

A (XLII I)

(XLIV)

(XLV)

(XLVI)

111© r e a c t i o n was c a r r ie d out i n p y r id in e w it h th e

a d d i t i o n o f a few drops o f p ip e r id i n e and a c r y s t a l l i n e compound o b ta in e d i n 60$ y i e l d .

A n a ly s is o f t h i s compound

showed i t t o be e i t h e r (2 L III) or (XLV);

t i t r a t i o n e x p e ri­

m ents s u g g e s t in g i t had i n f a c t th e l a t t e r s t r u c t u r e , and th e compound on c a t a l y t i c h y d r o g e n a tio n to o k up two atoms o f hydrogen to y i e l d th e d i b a s i c a c id ( X L Y I ) • P h t h a l i c anhydride on h e a t i n g w it h a c e t i c anhydride (2 7 ) and fu s e d p ota ssiu m a c e t a t e y i e l d s p h t h a l y l a c e t i c a c id

I f d ip h e n ic anhydride underwent an a n alogou s r e a c t i o n th e product would, on h y d r o g e n a tio n , y i e l d t h e a c id (XLVI) which c o u ld th u s be ob ta in ed w ith o u t th e n e c e s s i t y o f p rep a rin g th e h a l f ald eh y d e.

The r e a c t i o n betw een d ip h e n ic anhydride

and a c e t i c anhydride was t h e r e f o r e i n v e s t i g a t e d b u t d id n ot l e a d to any c r y s t a l l i n e p r o d u c t. The r in g c l o s u r e o f th e a c id (ZLVI) to a d ib e n z o y c l o h e p t a t r i e n e was attem p ted by t h r e e d i f f e r e n t r o u t e s . (24) S u b lim a tio n o f th e barium s a l t and tr e a tm e n t o f th e (25) sodium s a l t w it h a c e t i c anhydride was c a r r i e d out on hundred m illig r a m p o r t i o n s o f th e a c id -

I n each c a s e t h e

p rod u ct was an u n c r y s t a l l i s a b l e gum Y/hich c o u ld however be c o n v e r te d to a c r y s t a l l i n e 2 : 4 - d i n i t r o phenylhydrazone whioh was found, m e lt in g p o in t and mixed m e lt in g p o i n t , to be i d e n t i c a l w it h the 2 : 4 - d in itr o p h e n y lh y d r a z o n e o f 3 j 4 t 5 j6 d ib en zc y clo h e p ta -1 i3 :5 -trien e-7 -o n e.

The remainder o f th e

a c id , 280 m illig r a m s , was c o n v e r te d to i t s d im e th y l e s t e r by treatm en t w it h diazom ethane and t h e e s t e r s u b j e c t e d to th e Dieckmann c o n d e n s a t i o n ^ 6 ^. By tre a tm en t w it h sodium ( 7) i n benzene ( o f . , p . 626) 3 : 4 : 5 s 6 - d ib e n z c y c lo h e p t a - 3 s 5d i e n e - 2 - o n e - l — c a r b o x y lic e s t e r was o b ta in e d as an o i l . T h is o i l v/hen r e f l u x e d w ith d i l u t e s u lp h u r ic a c id d id n o t y i e l d th e d e s i r e d k e to n e and, s i n c e th e product was found to g i v e s t i l l the f e r r i c c h l o r i d e c o l o u r a t i o n c h a r a c t e r i s t i c o f th e Dieckmann e s t e r , th e trea tm en t w ith d i l u t e su lp h u r ic a c id was renev/ed.

The product from t h i s attem pted

h y d r o l y s i s wa s p u r i f i e d by d i s t i l l a t i o n and y i e l d e d a sm a ll amount o f l i q u i d d i s t i l l a t e which c o u ld n ot be c r y s t a l l i s e d .

Ho c r y s t a l l i n e k e to n e was o b ta in e d t h e r e f o r e from t h i s s y n t h e s i s alth o u g h th e gummy p r o d u cts o b ta in e d y i e l d e d th e 2 j4 - d in itr o p h e n y lh y d r a z o n e o f t h e d e s i r e d k e t o n e . With r eg a r d to method ( B ) , i . e . ,

r in g c l o s u r e o f

( s e e page 1 5 )

a phenylhydrocinnam ic a c id s e v e r a l c o n s i d e r a t i o n s emerge. 1) .

A ccording to v. B r a u n ^ 8 ^ r in g c l o s u r e to a five-memibered

r in g i s l i k e l y ,

c e t e r i s p a r ib u s , to tak e p r e fe r e n c e over

c l o s u r e t o a se v en membered r i n g . 2 ).

By a p p r o p r ia te s u b s t i t u t i o n i n t h e d ip h e n y l n u c le u s

seven-memberdd r in g fo rm a tio n m ight be f a c i l i t a t e d ;

more­

ov er th e u n sy m m e trica lly s u b s t i t u t e d d ip h e n y ls so r e q u ir e d would have th e advantage o f l e a d in g to u n sy m m e trica lly sub­ s t i t u t e d d ib e n z c y c lo h e p ta tr ie n e s. f h e s e c o n s i d e r a t i o n s have l e d to a g e n e r a l i n v e s t i g a t i o n o f t h i s method o f approach i n t h e s e l a b o r a t o r i e s , th e f o l lo w in g work b e i n g one p a r t i c u l a r a sp e c t w ith th e m a t e r i a l s and r o u t e proposed a s shown*-

/ \ (XLVII)

(XLVIII) (XLIX)

(LIXI)

(Ill) co — ~cnt

(LIV)

(LV)

fh e d i m e t h y l t r i a z e n e (XLYIII) was o b ta in e d from m ethyl a n t h r a n i l a t e b y d i a z o t i s a t i o n and c o a p lin g w ith d im eth y l amine.

I t was condensed w ith hydroqainone d im e th y l e th e r

to form th e ansym m etrical d ip h e n y l (XLIX) by t h e method o f E lk s and Hey (29) The c h o ic e o f hydroqainone d im eth y l e th e r as t h e component w it h which to condense th e t r i a z e n was governed b y th e f o l l o w i n g c o n s i d e r a t io n s 1 ).

I t e lim in a t e d th e p o s s i b i l i t y o f iso m e r s b e in g formed

d arin g t h e c o n d e n s a tio n s i n c e a l l p o s i t i o n s i n th e hydro­ qainone d im eth yl e th e r a t which c o a p lin g c o a id o c c a r are eq ai v a l e n t . 2 ).

She p r e se n c e o f an ortho methoxy groap m ight a c t i v a t e

p o s i t i o n 2 i n (L I I I ) and fa v o a r seven-membered r in g forma­ t i o n r a th e r than th e fo r m a tio n o f t h e hydrindone d e r i v a t i v e

I n p r a c tic e , by t b i s r o u t e t h e e s t e r (XLIZ) was o b t a in e d s a t i s f a c t o r i l y b a t i t was n o t p o s s i b l e to o b t a in i t s b y d ra z id e by r e a c t i o n w ith b y d r a z in e bydr a t e .

An

e t b a n o l i c s o l u t i o n o f tb e e s t e r wben r e f l u x e d f o r a week w i t b 99$ b y d r a z in e b y d r a te was not c o n v e r te d to t b e b y d r a z id e .

Tbe a c id was tb e n t r e a t e d w it b t h i o n y l c h l o r ­

id e under m ild c o n d i t i o n s i n an e f f o r t to o b t a in tb e a c id o b lo r id e .

Tbe compound o b ta in ed bov/ever was not tb e a c id

ch lo rid e ;

i t s a n a l y s i s co rr esp o n d s to tb e e m p ir ic a l

form u la CL ,&.-()* and i t s s t r u c t u r e w i l l t h e r e f o r e be e i t h e r 14 10 3 (L7I) or (L V II). CO

CO

'V

(I iYI)

° Me

(LVII)

Tbe flu o r e n o n e s t r u c t u r e i s u n l i k e l y s i n c e t b e compound i s alm ost c o l o u r l e s s wben pure and d o e s n o t g i v e tb e c h a r a c t e r i s t i c r e a c t i o n s o f p h e n o lic or ca rb o n y l g ro u p s. Tbe compound i s t h e r e f o r e assumed to have tb e l a o t o n i c s t r u c t u r e (LVII) and t b i s i s borne out by i t s b eh a v io u r w it b a l k a l i . S in c e n e i t h e r tb e a c id b y d ra zid e nor t b e a c id c h l o r ­ i d e c o u ld be o b ta in e d from t b e e s t e r (XLIZ), t b i s method bad t o be abandoned.

Experimental * D iph en ic a c id m o n o p h en y lsu lp h o n h yd razid e. (1 ) A c t io n o f H ydrazine H ydrate on D ip h en ic Anhydride. D iph en ic anhydride ( Z g . ) was t r e a t e d s l o w l y w ith h y d ra z in e h y d r a te {Z c c . t 90$) c o o l i n g b e in g a p p lie d to c o n t r o l t h e v ig o r o u s r e a c t i o n .

A fte r warming a t 100°G f o r

90 m in u tes w a ter was added and th e s o l u t i o n c a u t i o u s l y a c id ifie d .

The r e s u l t i n g s t i c k y mass s l o w l y s o l i d i f i e d .

I t was powdered and c r y s t a l l i s e d from e t h a n o l .

The f i l ­

te r e d n e e d le - s h a p e d c r y s t a l s appeared t o be homogeneous, s i n t e r e d c a 176°C and m elte d at 185°G w ith g a s e v o l u t i o n . Y i e ld , 1 . 2 g . ( 6 2 $ ) . T h is appears to be th e a c id b y d ra z id e (GQ^H; G Q .M .M g ) s i n c e i t d i s s o l v e s i n aqueous sodium b ic a r b o n a t e w itb e f f e r v e s c e n c e and t b i s r e s u l t c o n firm s t b e d e s c r i p t i o n / /zQ\ ( v i z . , m .p. 183°C) g iv e n to tb e compound b y l a b r i o l a i n c o n t r a s t to t h a t o f Kalb and Gross

(21)

o

, v i z . , m .p. 1 64WC

w itb foam ing. A c t io n o f b e n z e n e su lp h o n y l c h l o r i d e on above compound. A s u s p e n s io n o f t h e b y d ra z id e ( 1 . 3 g . ) i n p y r id in e (4 c c . ) was t r e a t e d i n t b e c o ld w itb benzene su lp h o n y l c h l o r i d e ( 1 0 .9 g . ) washed i n w itb p y r id in e ( Z oc .) .

Tbe

y e ll o w s o l u t i o n a f t e r sta n d in g o v e r n ig h t was d i l u t e d w itb

w a ter and a c i d i f i e d w it b d i l a t e s a l p b a r ic a c i d .

Ih e r e -

s a l t i n g p r e c i p i t a t e s o l i d i f i e d and was f i l t e r e d and washed fr e e o f a c id .

I t c r y s t a l l i s e d from d i l a t e e th a n o l a s a

r a t h e r n o n d e s c r ip t b a f f c o lo u r e d s o l i d , # . p .

(w ith some d e ­

c o m p o s it io n and p r e v io u s s i n t e r i n g ) 2 2 0°C.

Y i e ld , 1 . 9 g .

(94$) . (2 ).

A c tio n o f B en zen esa lp h on h yd razid e on D ip h en ic A n hyd ride. D ip h en ic anhydride ( 6 . 6 g . ) was added s l o w l y , w ith

c o o l i n g , to b e n zen esa lp h o n h y d ra zid e ( 5 . 1 g . ) i n p y r id in e (30 c c . ) .

A f t e r sta n d in g o v e r n ig h t i t was poured i n t o

d i l a t e h y d r o c h lo r ic a c id .

fh e o i l t h a t was p r e c i p i t a t e d

s l o w l y s o l i d i f i e d and was f i l t e r e d and washed w ith w a te r, m .p. 184°C.

The m .p. was r a i s e d to 2£0°C by r e p e a te d

c i y s t a l l i s a t i o n from d i l a t e e t h a n o l .

Y ie ld , 8 . 3 g . ( 7 0 $ ) .

The compound was s o l u b l e i n aqueous sodiam h y d ro x id e and sodiam ca rb on ate and was p r e c i p i t a t e d from t h e s e s o l u ­ t i o n s by su lp h u r d i o x i d e , but n o t by carbon d i o x i d e . i s th e

T h is

oi'. ft d i - a c y l b y d r a z id e , R.C O .M .M .SO ^Ph.

(Pound:

C, 6 0 .3 ;

0 , 6 0 .6 ;

H, 4 . 0 ;

H, 4 . 1 ; I,

I , 7 .3 $ .

^20^16^5^2^ r e q u i r e s

7 .1 $ ).

I n th e p u r i f i c a t i o n o f t h i s compound from t h e crude m a t e r i a l t h e r e was o b ta in e d from t h e e t h a n o l i c mother l i q u o r s a v e r y sm a ll amount o f an is o m e r ic s u b s t a n c e , m .p .

220°C, m ixed m.p* w ith above oompound 215 C. (Sound:

0 , 6 0 .8 ;

C, 6 0 .6 ;

H, 4 . 0 ;

H, 4 . 0 ;

IT, 6 . 9 $ .

C - J L , 0 . L S r eq u ire s au i o o 2

H, 7 .1 $ ) .

I b i s i s presumably t b e d - o i d i - a o y l b y d r a z id e , E.C0( SOgPbjH.HHg. She secon d method i s th u s t h e sim p le r and more e ffic ie n t in th is case.

Only th e main p rod u ct was su b ­

j e c t e d to M eP adyen-Stevens’ d e c o m p o sitio n , i n s u f f i c i e n t o f t h e o th e r isom er b e in g o b ta in e d f o r d e t a i l e d i n v e s t i g a t i o n . H-benzenesulphonamino p h t h a lim id e . P h t h a l i c anhydride (5 g . ) was s l o w l y added t o a s o l u t i o n o f b e n zen esa lp h o n h y d ra zid e ( 5 . 8 g . ) i n p y r id in e (18 c c . ) .

A fte r sta n d in g o v e r n ig h t th e s o l u t i o n was poured

i n t o d i l u t e h y d r o c h lo r ic a c i d .

The r e s u l t i n g s o l i d was

c r y s t a l l i s e d from g l a c i a l a c e t i c a c id and had m .p. 262°G. I t was s o l u b l e i n aqueous sodium h yd roxid e and sodium c a r ­ b on ate and was r e p r e c i p i t a t e d by su lph ur d i o x i d e , b u t n o t by carbon d i o x i d e . (Pound:

D, 5 5 .4 ;

0 , 5 5 .6 ;

H, 5 . 3 ;

Y i e ld , 6 .6 g . ( 6 6 $ ) . H, 3 . 2 ;

Iff, 9 . 1 $ .

G14 S i q ° 4 H2 S r e q u i r e s

B, 9 . 3 $ ) .

Attempted M cPadyen-Stevens1 D ecom p osition o f 3ff-benzenesulphonamino p h t h a lim id e . B-benzenesulphonamino p h th a lim id e (4 g . ) i n e t h y l ­ ene g l y c o l (50 c c . ) was t r e a t e d w ith sodium c a rb o n a te ( 7 . 7 g . )

i

a t 160°G.

The a l k a l i was added i n t h e c o a r s e o f 30 se c o n d s

nnfl th e r e a c t i o n a llo w e d to p roceed f o r a f a r t h e r 240 secon ds* The r e a c t i o n was te r m in a te d by t h e c a r e f u l a d d i t i o n o f b o i l ­ in g w a ter (1 00 o c . ) and th e c o o le d s o l u t i o n was f i l t e r e d through c h a r c o a l .

There was no p r e c i p i t a t e formed on t r e a t ­

in g th e f i l t r a t e w ith sulphur d i o x i d e .

A c i d i f i c a t i o n w it h

d i l u t e su lp h u r ic a c id p r e c i p i t a t e d p h t h a l i c a c i d .

There

was no t r a c e o f any a ld e h y d ic p r o d u ct. 2 1- f o r m y l d i p h e n y l - 2 - c a r b o x y l ic a c id (X I X I ) . D iphenic a c id m onophenylsulphohhydrazide ( 2 g . ) i n e t h y le n e g l y c o l (20 c c . ) was t r e a t e d w ith sodiam carb on ate ( £ . 5 g . ) at 165°G.

The a l k a l i was added i n th e c o u r se o f

30 seco n d s and th e r e a c t i o n a llo w e d to p ro c ee d f o r a f u r t h e r 240 se c o n d s, when i t was te r m in a te d by th e c a r e f u l a d d i t i o n o f b o i l i n g w ater (up to 100 c c . ) .

A ft e r c o o l i n g and f i l ­

t e r i n g through c h a r c o a l to remove suspended m a tte r , su lp h u r d io x id e was p a sse d i n t o th e s o l u t i o n t i l l t h e r e was no fu rth er p r e c ip it a t io n .

This p r e o i p i t a t e d m a t e r i a l was r e ­

c r y s t a l l i s e d from d i l u t e m ethanol and th e n had m .p . 220°G. I t did n o t d e p r e ss th e m e l t i n g p o in t o f th e monophenylsu ip h on h yd razid e o f d ip h e n ic a c id and was r e - t r e a t e d i n l a t e r runs.

When th e s o l u t i o n no l o n g e r gave a p r e c i p i t a t e w it h

sulphur d io x id e i t was a c i d i f i e d w ith d i l u t e su lp h u r ic a c i d . A s o l i d was s l o w l y p r e c i p i t a t e d , o f which th e m e l t i n g p o in t

a f t e r c r y s t a l l i s a t i o n from d i l a t e m ethanol was 132°C. Y i e ld , 0 .5 1 g . ( 4 5 $ ) . (Round:

0, 7 4 .5 ;

H, 4 . 4 $ .

Gi4.2 i o 03 rQC~- c .

'

.’

\

.

i) •'

o

/;'-X , )

. '

D i s c u s s io n . The s t a r t i n g m a te r ia l employed in the s y n t h e s i s o f t h e n a p h th a len e d i o l s was 1 j 2 - dihydro nap hth alen e o b ta in e d from a . c . - t e t r a h y d r o - jh -naphthol by th e method o f Bamberger and L od ter^ 15^. S e v e r a l methods f o r o b ta in in g d l - o i s - and d l - t r a n s lj 2 - d i h y d r o x y - l : 2 j 3 : 4 - t e t r a b y d r o n a p h t h a le n e from 1 : 2 d ih yd ron ap h th alen e were s tu d ie d . G r i e g e e ^ ^ has d e sc rib ed a method f o r s y n t h e s i s i n g o i s - d i o l s from u n satu rated hydrocarbons by th e fo rm a tio n o f osmic a c id e s t e r s and t h e i r subsequent h y d r o l y s i s . >C 0 O >C — C) I 4Os -----------> I >C O >C ~

0

05

X -o tf ----------> >C~O H

The a p p lic a t io n o f t h i s method to l i 2 - dih ydron a p h th a le n e gave a hydroxy compound which was assumed to be d l - o i s - 1: 2 - d ih y d r o x y -1 : 2 : 3 :4-1etrahydronaphthalene .

The

same compound was obtained by t r e a t i n g th e dihydronaphthalene w ith hydrogen peroxide i n t e r t i a r y b u t y l a lc o h o l i n th e p r e s e n c e o f osmium t e t r o x i d e (compare M ila s and Sussman l e i t h e r o f t h e s e methods however was s u i t a b l e f o r th e p r e ­ p a r a t i o n o f th e la r g e q u a n tity o f d i o l r eq u ire d f o r th e u l t i m a t e r e s o l u t i o n in to the two o p t i c a l l y a c t i v e form s:

^) .

64.

t h e form er because o f th e r e l a t i v e l y l a r g e amount o f c o s t l y osmium t e t r o x i d e r e q u ir e d ; y i e l d o b t a in e d .

th e l a t t e r b e c a u se o f th e low

3?|ie experim ents o f S tr a u s and B o h r b a c h e r ^ ^

who claim ed t o o b t a in from 1 : 2 - dihydro nap h th alen e th e c i a d i o l by p ota ssiu m permanganate o x i d a t i o n and th e t r a n s - d i o l by s t e p w is e h y d r o l y s i s o f the dibromo compound, were t h e r e ­ f o r e r e p e a te d and proved to be s u i t a b l e p r e p a r a tiv e m ethods. The d i o l o b ta in e d by p otassiu m permanganate o x i d a t i o n was i d e n t i c a l w ith t h e c i s - d i o l a lr e a d y o b ta in e d and t h e r e f o r e t h e d i f f e r e n t compound o b tain ed by h y d r o l y s i s o f th e d i bromide was assumed to be t r a n s - d i o l .

The l a t t e r compound

was a l s o o b ta in e d by t r e a t i n g dihydronaphthalene w ith hydrogen p ero xid e i n t e r t i a r y b u t y l a l c o h o l i n th e p r e se n c e . (19) o f se le n iu m d i o x i d e , a method claim ed by Segum to y i e l d t h e t r a n s c o n f i g u r a t io n . f h e c o n f i g u r a t io n a s s ig n e d to t h e s e d i o l s was co n ­ firm ed by a stu d y o f t h e i r r a t e o f o x id a t io n w it h l e a d tetra -a ceta te,

s i n c e C riegee^ 2 0 ^ h as shown th a t l e a d t e t r a ­

a c e t a t e i n v a r i a b l y o x i d i s e s c y c l i c o i s - l : 2 - d i o l s much more r a p i d l y th an th e t r a n s - is o m e r id e s by a r e a c t i o n which may be sy m b o lised t h u s : -C.-OH

' 2 0 A

c ---------------- ^

e +■ Z H

-0 = 0

+ Z .O A c

F I Cr.

The graph o f th e r e s a l t s o b ta in ed h er e ( s e e t f i g . l j i l l u s t r a t th e u s e f u l n e s s o f th e method f o r d i s t i n g u i s h i n g betw een c i s and t r a n s - d i o l s o f t h i s t y p e . Another r ea g en t d e s c r ib e d b y O riegee d e te r m in in g th e c o n f i g u r a t io n o f d i o l s i s p o ta ssiu m t r i a c e t y l o sm ia te ( 2 ) .

This compound forms d l - e s t e r s o f th e

ty p e ( 2 1 ) w ith such d i o l s as have two s u i t a b l e h yd rox yl g ro u p s, s p a t i a l l y fa v o u ra b le to th e r in g c l o s u r e , a t t h e i r d i s p o s a l and t h e r e f o r e m ainly w ith

dC - d i o l s having a c i s -

o o n fig u r a tio n . C H jC o .O

CH3 C0 O

0

ococh3

> C -0 H

>C — o

OK

>c-ort

>c — o

0

(XU

(z)

A s o l u t i o n o f th e r ea g en t i n a c e t i c a c id has a

r o y a l b lu e c o lo u r and the fo rm a tio n o f d i - e s t e r s i s accompanied by a marked c o lo u r change.

The t e s t i s t h e r e ­

f o r e v e r y sim p ly c a r r ie d out by a d d it io n o f th e d i o l to th e s o l u t i o n o f t h e reagen t and i s p a r t i c u l a r l y v a lu a b le i n b e i n g c a p a b le o f a p p l i c a t i o n on a micro s c a l e . I t i s o f p a r t i c u l a r i n t e r e s t i n th e p r e s e n t con ­ n e c t i o n t h a t C riegee^ 21^ has rep o rted t r a n s - 1 :2 - dih ydroxy1 s2

. 4 - tetrahydr© naphthalene to be e x c e p t i o n a l ( l i k e

t r a n s - o y c lo h e x a n e - 1 : 2 - d i o l ) i n forming a d i - e s t e r w ith

p o ta s siu m t r i a c e t y l o sm ia te .

Booth and B o y l a n d ^ i , however,

w ith o u t comment on G r ie g e e ! s f i n d i n g , s t a t e t h a t th e r ea g e n t p r o v id e s th e u su a l d i s t i n c t i o n betw een th e c i s - and t r a n s ­ form s-

R e -ex a m in a tio n o f t h i s p o in t showed t h a t th e r e i s

i n f a c t a marked d i f f e r e n c e i n th e behaviou r o f th e two form s;

th e c is - f o r m g i v in g an immediate c o lo u r change

w hereas th e t r a n s -form in d u ces o n ly a slow and l e s s pronounced m o d i f i c a t i o n o f th e c o lo u r .

G riegee

(29)

, l i k e Booth and

B oyland , prepared th e t r a n s - d i o l by le a d t e t r a - a c e t a t e o x i d a t i o n o f 1 : 2 -dihydro naphthalene and i t may be n oted t h a t i n th e anth racen e s e r i e s ( c f . p . 12. ) t h i s procedure h a s been found to a f fo r d a m ixture o f c i s - and t r a n s - d i o l s ♦ P o s s i b l y , t h e r e f o r e , co n ta m in a tion w ith the c i s -iso m e r i n p a r t a cco u n ts f o r G r ie g e e f s c o n c lu s io n th a t th e abovem entioned t r a n s - d i o l shows e x c e p t i o n a l b e h a v io u r . Jlot a l l th e methods which have been a p p lie d to t h e r e s o l u t i o n o f a l c o h o ls are a p p lic a b le to d i o l s ,

and not

many exam ples o f th e s u c c e s s f u l r e s o l u t i o n o f d i o l s are r eco rd ed i n t h e l i t e r a t u r e . f o r the r e s o l u t i o n o f th e nap h th alen e d i o l s a new r e s o l v i n g a g e n t, 3,-menthoxy a c e t i c a c id , in tro d u ced by Read and h i s a s s o c i a t e s and s u c c e s s f u l l y employed f o r th e (22) r e s o lu t io n o f d l - tra n s- l : 2 -cy c lo h ex a n e-d io l was con ­ s i d e r e d to be th e most p rom isin g.

The b a s i s o f t h i s

method o f r e s o l u t i o n i s the fo rm a tio n o f a s o l i d e s t e r and its

su bseq uent s e p a r a t io n by f r a c t i o n a l c r y s t a l l i s a t i o n

i n t o t h e two d ia s te r e o is o m e r ic forms from which the a c t i v e d i o l and r e s o l v i n g agent are rec o v er ed by h y d r o l y s i s .

It

was n e c e s s a r y t h e r e f o r e to a s c e r t a i n t h a t th e 1 -menthoxya c e t i c a c id would form a s o l i d e s t e r w it h th e d i o l . I 22) W ilson and Head found th a t i n th e r e a c t i o n b etw een d l - t r a n s - 1 : 2 - c y c l o h e x a n e - d i o l and ].-m en th oxyacetyl c h l o r i d e o n ly th e m on o-ester was formed even when two e q u i v a l e n t s o f th e a c id c h lo r id e were employed. When d l - t r a n s - 1 : 2 - d i h y d r o x y - l : 2 s 3 : 4 - t e t r a h y d r o n a p h th a le n e was t r e a t e d i n dry p y r id in e w ith e i t h e r 1 or 1 . 5 e q u i v a l e n t s o f a c id c h lo r id e a s o l i d e s t e r was o b ta in e d

which was ho?/ever contam inated ?dth u n e s t e r i f i e d d i o l .

An

attem p t was t h e r e f o r e made to o b ta in a d i - e s t e r by t r e a t i n g th e m o n o -e ste r o b ta in ed above w ith a f u r t h e r 1 . 5 e q u i v a l e n t s o f a c id c h l o r i d e .

Ehe c r y s t a l l i n e e s t e r ob ta in ed i n t h i s

way was shown to be a d i - e s t e r by an exam in a tion o f i t s s a p o n ific a tio n v a lu e.

I t i s not p o s s i b l e to d i s t i n g u i s h

th e m o n o -e ste r from th e d i - e s t e r a n a l y t i c a l l y : ester,

re(lu i r e s

7 3 *3 3 ’* H>

e s t e r , g 34 H5 2 0 6 ,

r e q u ir e s G, 7 3 .3 8 ;

th e mono&n& th e d i ­

H, 9 . 3 5 $ .

fhe d i - e s t e r was se p a r a ted i n t o i t s d ia s t e r e o is o m e r io forms b y lo n g f r a c t i o n a l c r y s t a l l i s a t i o n from petroleum

eth er.

Approxim ately equal amounts o f th e two d i a s t e r e o -

i s o m e r i d e s were u l t i m a t e l y o b ta in ed ; m#p. 116-117°G

[U \

-2 1 ° ( c , 1 i n chloroform ) and th e

more s o l u b l e , m .p. 101-102°C c h lo r o f o r m ).

th e l e s s s o l u b l e had

[oO,' -1 7 0 ° (o , 1 i n

Ihe e s t e r o f m.p. 116-1 17° when h y d r o ly s e d

w ith a l c o h o l i c p otassiu m hydroxide y i e l d e d 1 - t r a n s - 1 : 2 d ih y d r o x y - 1 : 2 j 3 :4 - 1 etrahydronaphthal ene ( o , 1 i n c h lo r o f o r m ) .

M"

-1 3 4 °

The e s t e r o f m .p . 101-102°C s im i-

l a r l y y i e l d e d d - t r a n s - 1 : 2 - d ih yd ro xy- 1 : 2 s 3 ? 4 -te tr a h y d r o r o n a p h th a len e 132 (c , 1 i n c h lo r o fo r m ). Phe m e ta b o lic product i s a dihydro n ap hth alen e d e r i v a t i v e and on c a t a l y t i c hyd rogen ation w ith a platinum c a t a l y s t y i e l d s a d e x tr o r o ta to r y l ; 2 - d i h y d r o x y - l : 2 j 3 ; 4 t e tr a h y d r o n a p h t h a le n e .

A specimen o f t h i s hydrogenated

m e t a b o l i t e , k in d ly s u p p lie d by P r o f e s s o r Young, was found to be i d e n t i c a l w ith d -t r a n s - 1 ; 2 - d ih y d r o x y -1 ; 2 13,*4-t e t r a h yd ron ap h th a len e, mixed m e ltin g p o in t and s p e c i f i c r o t a t i o n , and mixed m e ltin g p o in t o f th e d i a c e t a t e s .

Phis i s i n (9) agreement w ith the c o n c lu s io n o f Booth and Boyland , th a t t h e n ap hth alen e m e t a b o lit e s have th e t r a n s - c o n f i g u r a t i o n . A p r e lim in a r y i n v e s t i g a t i o n o f th e e s t e r i f i c a t i o n o f d l - c i s - l : 2 : d ih y d r o x y - l: 2 j 3 ; 4 -te tr a h y d r o n a p h th a le n 0 w ith 1 -m en th o x y a cety l c h lo r id e in d ic a t e d t h a t a s o l i d e s t e r c o u ld

be o b ta in ed by t r e a t i n g th e d i o l w ith one e q u iv a le n t o f a c id

c h lo rid e .

When, however, i t was d is c o v e r e d t h a t th e t r a n s -

d i o l co u ld be r e s o lv e d by f r a c t i o n a t i o n o f i t s d i - e s t e r i t was d e c id ed to form a d i - e s t e r from th e c i s - d i o l a l s o . Treatment o f t h e d i o l w ith 2 .5 e q u iv a le n t s o f a c id c h l o r i d e gave r i s e to an o i l y product which co u ld not be s o l i d i f i e d . The o r i g i n a l experim ent y i e l d i n g a s o l i d e s t e r by trea tm en t w it h one e q u iv a le n t o f acid c h lo r id e could not be rep ea ted and a c c o r d in g ly a se a rc h was made fo r another reagen t w ith which to e f f e c t th e r e s o l u t i o n o f t h e c i s - d i o l . Glark and •R e a d h a v e

r e p o r te d a s u c c e s s f u l

r e e o l u t i o n o f dl~m enthol b y means o f a new r e s o l v i n g a g e n t, J L -m en th y lg lycin e.

E s t e r s o f t h i s a c id are o b ta in e d by

e s t e r i f y i n g the racemic a lc o h o l w ith c h l o r a c e t y l c h l o r i d e and t r e a t i n g th e c h lo r o a c e t a t e w ith 1 -ment by lamina s . OH 0 1 0 H3 000 ,3: )

g . o CO CHgCl

E . 0 .CO CHg.BH C10 H19

The r e s u l t i n g d ia s t e r e o is o m e r ic 1 -m e n th y lg ly c in e e s t e r s are se p a r a te d by c r y s t a l l i s a t i o n and th e a c t i v e a lc o h o l i s r e ­ c o v e r e d from each form by h y d r o l y s i s .

‘The m a j o r it y o f

t h e s e e s t e r s are c r y s t a l l i n e s o l i d s and t h e y y i e l d c r y s t a l ­ l i n e s a l t s w ith a c id s and c r y s t a l l i n e LT- a c y l d e r i v a t i v e s . Treatment o f th e d l - c i s - d i o l w ith c h l o r a c e t y l c h l o r i d e l e d to an o i l y product which was assumed to be th e d esir ed d i-e h lo r o a c e ta te .

Treatment o f t h i s o i l w ith

l.-m en th yl amine e i t h e r under th e c o n d i t i o n s d e s c r ib e d by / OA } Head or i n th e c o ld y i e l d e d o n ly a gummy m a t e r i a l . 3Jo r e s o l u t i o n t h e r e f o r e cou ld be ac h iev e d by t h i s meansf a i l u r e to r e s o l v e the c i s - d i o l may be due to a sterie e f f e c t which would hin d er th e fo rm a tio n o f a di~ e s t e r w ith t h e r e s o l v i n g a g en ts employed.

fh e r eq u ir e d

s t a r t i n g m a t e r ia l f o r the p r e p a r a tio n o f c i s - and t r a n s 1

d ih y d r o x y -I : 2 : 3 : 4 - tetrah yd ro an th racen e was l : 2 - d ih y d r o -

anth ra cen e which i t was hoped to o b ta in from 1 : 2 : 3 : 4 - t e t r a ­ hydro - 2 - ant h ro 1 . 2 - a n t h r o l was ob tain ed from a n th ra q u in o n e- 2 -

sodium su lp h o n a te by r e d u c tio n w ith z in c d u st and ammonia (26) to a n th r a c e n e - 2 - sodium su lph onate and f u s io n w ith (27) p o ta ssiu m h y d ro x id e . fh e 2 - a n t h r o l was p u r i f i e d by s u b lim a t io n under reduced p r e ssu re and c r y s t a l l i s a t i o n o f th e s u b lim a te from b en zen e. Chemical r e d u c tio n o f 2 - a n t h r o l l e a d s t o th e 9 :1 0 (25) dihydro d e r i v a t i v e but v . Braun and Bayer have r e p o r te d t h a t the 1 : 2 : 3 : 4 - tetrah yd ro d e r i v a t i v e i s a l s o formed when 2 - a n t h r o l i s su b je c te d to h igh p r e s s u r e h y d rogen ation i n

th e p r e se n c e o f n i c k e l s a l t s .

She use o f copper chrom ite

as a c a t a l y s t i n the high p r e ssu re h y d ro gen ation o f 2 n a p h th o l l e a d s to an 80$ y i e l d o f 1 : 2 : 3 : 4 - t e tr a h y d r o - 2 (28) n a p h th o l

2 -A n th r o l was t h e r e f o r e hydrogenated under p r e ssu r e i n t h e p r e s e n c e o f copper chromite andpwas con verted i n 60$ y i e l d to 1 : 2 : 3 : 4 - t e t r a h y d r o - 2 - a n t h r o l to g e t h e r w ith a s m a ll amount o f 9 : 1 0 - d ih y d r o -2 -a n t h r o l.

v . Braun r e p o r t e d

t h a t th e d e h y d ra tio n o f 1 : 2 : 3 : 4 - t e t r a h y d r o - 2 - a n t h r o l to 1 .*2 - d ih yd roan th racen e d id not take p la c e r e a d i l y but c o u ld

be a c h ie v e d by d i s t i l l a t i o n o f i t s pheny lu r e t h a n e .

This

method o f d e h y d ra tio n was examined but found t o be u n s a t i s ­ fa cto ry .

B e t t e r r e s u l t s were o b ta in ed by h e a t in g t h e

t e t r a h y d r o a n th r o 1 w ith f r e s h l y fu sed potassiu m h y d r o x id e . The 1 : 2 - dihydro anthracene was t r e a t e d w it h osmium t e t r o x i d e i n an e th er s o l u t i o n c o n t a in in g p y r id in e a c co r d in g to C r i e g e e ' s

(

21)

m o d if ic a t io n o f h i s e a r l i e r p r o c ed u r e.

H y d r o ly s is o f th e osmium-pyridine adduct y i e l d e d d l - c i s - 1 : 2 d ih y d r o x y - l: 2 : 3 : 4 - t e t r a h y d r o anthracene . I n order to o b ta in th e t r a n s - d i o l th e method found to be s u c c e s s f u l i n th e naphthalene s e r i e s ;

v i z . , th e

s t e p w is e h y d r o l y s i s o f th e dibrom ide, was a p p lie d to 1 : 2 d ih y d r o a n th ra d en e .

The dibromide was r e a d i l y o b ta in e d

and c o n v e r te d to 1 ( 2 j-brom o- 2 ( l ) - h y d r o x y - 1 : 2 : 3 : 4 - te tr a h y d r o a n th ra cen e i n s a t i s f a c t o r y y i e l d .

The h y d r o l y s is o f t h i s

hydroxybromide gave the d e s ir e d t r a n s - d i o l but i n r a t h e r poor y i e l d . Treatment o f u n sa tu rated hydrocarbons w ith l e a d

72.

t e t r a - a c e t a t e a f f o r d s , g e n e r a lly , t h e dl a c e t a t e o f th e t r a n s d i o l h a t i n some c a s e s th e c i s - d i o l d i a c e t a t e i s a ls o (29) formed . A sm a ll amoant o f 1 : 2 - dihydro anthracene was t r e a t e d w it h le a d t e t r a a c e t a t e and t h e o i l y product o b ta in e d was h y d r o ly s e d w ith a l c o h o l i c p otassiu m h y d r o x id e .

d l-tr a n s-

1 : 2 -D ih y d r o x y -1 :2 iZ :4 -tetr a h y d ro a n th r a ce n e was th e r e b y o b t a in e d i n 64$ y i e l d from th e dihydro ant hr ac ene .

The

method was t h e r e f o r e a p p lie d to th e b u lk o f th e d ih yd ro­ a n th racen e b u t i n t h i s c a se the product a f t e r h y d r o l y s is was a m ixtu re o f c i s - and t r a n s - d i o l s .

A p a r t i a l s e p a r a t io n

o f t h i s m ixture was e f f e c t e d by f r a c t i o n a l c r y s t a l l i s a t i o n from b e n z e n e .

During the s e p a r a t io n a sm a ll amount o f a

h ig h m e ltin g compound o f unknown c o n s t i t u t i o n was i s o l a t e d . The c o r r e c t n e s s o f the c o n f i g u r a t io n a s s ig n e d to t h e s e d i o l s was confirmed by a stu d y o f t h e i r r a t e o f o x i ­ d a t i o n by l e a d t e t r a - a c e t a t e and t h e i r colou r change on tre a tm en t w ith potassium t r i a c e t y l osm iate reagent^'

^•

I t was found t h a t , as i n th e c a s e o f th e n a p h th a l­ ene d i o l s , th e c i s - d i o l was o x i d i s e d much more r a p i d l y than t h e t r a n s - d i o l by le a d t e t r a - a c e t a t e ( s e e F i g . 2) . Boyland and Shoppee^3 0^ have measured t h e r a t e o f o x i d a t i o n o f t h e m eta b o lic 1 : 2 - dihydroxy - 1 .*2 - dihydro a n th ra ­ cen e w ith le a d

t e t r a -

acetate.

In doin g so t h e y took in to

c o n s i d e r a t io n th e r e a c t i v i t y of the meso p o s i t i o n s o f th e

a n th ra c en e system towards t h i s r e a g e n t .

fhu s Meyer^3 1 ^ had

found t h a t anthracene was o x id is e d by a s o l u t i o n o f l e a d d i o x i d e i n a c e t i c a c id ;

the product b ein g anth ran yl a c e t a t e

when one m o le c u le o f le a d d io xid e was employed and mesoh y d r o x y a n th r a n y la c e ta te when two m o le c u le s o f r ea g en t are used.

L a te r if ie s e r ^ 3 2 ^ showed t h a t l e a d t e t r a - a c e t a t e i n

a c e t i c a c i d i s e q u iv a le n t to th e le a d d i o x i d e - a c e t i c a c id m ix tu re used by Meyer.

Boyland and Shoppee, t h e r e f o r e ,

a n t i c i p a t e d th a t the dihydroxydihydroanthracene would be a t t a c h e d at the $ e so p o s i t i o n s and would r e q u ir e two m ole­ c u l e s o f l e a d t e t r a - a c e t a t e for i t s o x id a t io n , and have r e p o r t e d t h a t , in f a c t , t h i s i s s o . N e v e r t h e le s s , t h e i r f i g u r e s , v i z . ^ 4 0 0 0 mole o f d i o l r e q u ir e 5 oc . 1 m ole = 20 l i t r e s

Mi

N/

10 le a d t e t r a - a c e t a t e (and hence 10 = 2 l i t r e s 1 = 1

mole o f l e a d t e t r a ­

a c e t a t e ) which are in good agreement w ith th o s e o b ta in ed h e r e f o r th e o x id a t io n o f c i s - and t r a n s - 1 : 2 - d i h y d r o x y - l : 2 : 3 : 4 t e t r a h y d r o a n th r a c e n e , i n d ic a t e t h a t on ly one m o lec u le o f l e a d t e t r a - a c e t a t e i s r e q u ir e d .

f h i s i s i n accordance w ith

t h e e x p erim en ts recorded here on t h e trea tm en t o f 1 : 2 - d i ­ hydro anthracene w ith le a d t e t r a - a c e t a t e where t h e meso p o s i t i o n s o f the hydrocarbon are unattached a f t e r one h o u r 's h e a t i n g at 90 °G.

74.

That t h e meso |)O sitio n s i n t h e s e hydrogenated a n th racen e d e r i v a t i v e s are unattached by le a d t e t r a - a c e t a t e i s not c o n t r a r y to t h e o r e t i c a l e x p e c t a t i o n s s in c e i t i s a f a l s e a n a lo g y to compare them w ith th e meso p o s i t i o n s of a n th racen e i t s e l f . When the potassium t r i a c e t y l osm iate r e a g e n t was a p p lie d to t h e anthracene d i o l s the p r e v io u s d e te r m in a t io n o f t h e i r c o n f i g u r a t io n was confirm ed. The r e s o l u t i o n o f th e anthracene d i o l s was attem pted u s in g as r e s o l v i n g agent 1 -m en thoxyacetic a c id .

The d l -

t r a n s - d i o l on treatm en t with fou r m o le c u le s o f 1 -menthoxya c e t y l c h l o r i d e y i e l d e d a red dish c o lo u r e d o i l .

Attem pts

to in d u ce t h i s o i l to s o l i d i f y by su b lim a tio n , chromato­ graphy and renev/ed a c y la t i o n , as w e l l as by th e u su a l m ethods, a l l f a i l e d .

The p u r i t y o f th e d i o l was checked

by c o n v e r t in g i t to a c r y s t a l l i n e d i a c e t a t e v/hich was p u r i ­ f i e d and h y d r o ly se d to r e g e n e r a te the d io l=

The d i o l

o b ta in e d i n t h i s way showed no change i n m e ltin g p o in t and s t i l l gave an o i l on treatm ent with 1 -menthoxy a c e t y l c h l o r ­ id e .

The d l - c i s - d i o l s i m i l a r l y f a i l e d to y i e l d a s o l i d

e s t e r , though i t i s notew orthy t h a t i n t h i s c a se th e r e was a much l e s s marked co lou r produ ction on a d d i t io n o f th e a o id c h l o r i d e to the d i o l s o l u t i o n and th e o i l ob ta in ed was alm ost c o l o u r l e s s .

The d ih y d r id e o f th e o p t i c a l l y i n a c t i v e anthracene (1) m e t a b o l i t e has been d e sc r ib e d by Boyland and L e v iv ' and i t s p h y s i c a l p r o p e r t i e s , m e ltin g p o in t and m e lt in g p o in t o f its

d i a c e t a t e , are i n concordance w ith t h o s e o f d l - t r a n s ­

i t 2- & ih y d ro x y -l: 2 * 3 :4 - tetrabyd ro anth racen e.

I t appears

t h e r e f o r e t h a t t h e anthracene m e t a b o lit e a l s o h a s th e t r a n s - c o n f i g u r a t i o n althou gh i t has not been p o s s i b l e to o b t a i n a specim en o f the dihydro m e t a b o lit e f o r d i r e c t com­ p a r i s o n w i t h t h e s y n t h e t ic d io l*

B x p e r im e n ta l. 1 ; 2 -D ih y d r o n a p h th a le n e . 1 *2 - Dihydro naphthalene was o b ta in e d from a . c - t e t r a -

h y d r o - p - n a p h t h o l as a c o l o u r l e s s o i l , b . p . 9 8 -1 0 0 ° G /l4 mm., i n 80$ y i e l d b y t h e method o f Bamberger and L o d t e r ^ ^ . d l - o i a - l * 2 - d i h y d r o x y - l > 2* g*4-tetrah yd ron ap h th alen e. A) •

O x id a tio n o f 1 * 2 - dihydronaphthalene w ith osmium t e t r o x i d e

( c f . Q r ie g e e ^16 ^) . Osmium t e t r o x i d e (2 g . ) was d i s s o l v e d i n d r y e th e r (4 0 cc .) and 1 s2 - dihydronaphthalene ( 1 . 0 4 g . ) added. s o l u t i o n darkened im m ed iately.

The

A fte r stan ding f o r s e v e n

days th e e t h e r was removed and th e b la c k osmic e s t e r r e ­ f l u x e d f o r th r ee hours w ith a s o l u t i o n o f sodium s u l p h i t e h e p ta h y d r a te ( 8 g . ) i n 7/ a t e r (40 c c . )

and e th a n o l (20 c c . ) .

The s o l u t i o n was f i l t e r e d hot and the sodium osmium s u l p h i t e r e f l u x e d f o r 30 m inutes w ith e th a n o l.

The s o l u t i o n was a g a in

f i l t e r e d and most of t h e a lc o h o l removed frcm th e combined f i l t r a t e s on t h e w ater b a t h .

The s o l u t i o n was t h e n e x t r a c t e d

t h r e e t im e s w ith 50 c c . chloroform and t h e chloroform e x t r a c t s d r ie d and c o n c e n tr a te d .

The s o l i d o b ta in ed was p u rp le i n

c o l o u r , but a f t e r r e f l u x i n g i n benzene w ith a l i t t l e c h a r c o a l i t was o b ta in ed by c r y s t a l l i s a t i o n from benzene as c o l o u r l e s s l a m e l l a e , m. p. 101°G.

Y ie ld , 0.76 g . ( 6 5 $ ) .

Bj.

O x id a tio n o f Is 2 - dihydronaphthalene w ith p o ta ssiu m

perm an ganate. By th e method o f Straus and Rohrbacher

(18)

th e d i o l

was o b ta in e d i n 20$ y i e l d , m.p. 100-101°G . 0 ).

O x id a tio n o f 1 : 2 - dihydronaphthalene w ith hydrogen p e r ­

o x id e i n th e p re sen ce o f osmium t e t r o x i d e ( o f . M ila s and Su ssm an ^ ^ ) . The hydrogen p e r o x id e r e a g e n t. Hydrogen peroxid e (5 c c . ,

90$ by w e ig h t) was d i s ­

s o l v e d i n t e r t i a r y b u ty l a lc o h o l (50 c c . )

and th e s o l u t i o n

d r ie d o v er anhydrous sodium s u lp h a t e . 1 : 2-Dihydronaphthalene ( l g . ) was mixed w it h an e q u im o le c u la r q u a n tity o f the p eroxid e rea gen t ( 3 . 2 5 cc . ; o 0 . 2 6 g . ) and the m ixture c o o le d to 0 0 i n an i c e b a th . To th e c o o le d s o l u t i o n was then added th e c a t a l y s t ;

a so lu tio n

o f osmium t e t r o x i d e ( 0*1 g*) i n t e r t i a r y b u t y l a lc o h o l (10 c c . ) .

The m ixture was kept at 0°G f o r e ig h t d a y s.

The

s o l u t i o n was then evaporated to d ryn ess under reduced p r e s s u r e and th e r e s i d u a l dark b lu e t a r e x t r a c t e d s e v e r a l tim e s w ith b o i l i n g w a te r .

The aqueous e x t r a c t on concen­

t r a t i o n y i e l d e d a dark brown o i l 7/hich was d i s s o l v e d i n benzene and r e f lu x e d w ith c h a r c o a l.

Petroleum e th e r (60 -

8 0 ° 0 ) was added to the f i l t e r e d benzene s o l u t i o n t i l l a

permanent t u r b i d i t y was produced and th e s o l u t i o n k e p t o v e r n ig h t.

The s o l i d m a t e r ia l which was d e p o s it e d was

washed f r e e o f th e o i l s t i l l adhering to i t and c r y s t a l l i s e d from b e n z e n e , m.p. 99-100°C . in g p o in t o f pure c i s - d i o l .

I t did not d ep ress t h e m e l t ­ Y ield o f d i o l 4-0 mgs.

d l-c is -l:2 -d ia o e to x y -l:2 :3 :4 -te tr a h y d r o n a p h th a le n Q . d l - c i s - 1 : 2 - d ih y d r o x y -1 : 2 : 3 : 4 - tetr a h y d ro n a p h th a len e was a c e t y l a t e d by treatm ent w ith a c e t i c anhydride i n p y r id in e in th e c o ld .

The d i a c e t a t e was p u r i f i e d by c r y s t a l l i s a t i o n

from p etro leu m e t h e r ( > 1 2 0 ° ) , m .p. 78°G.

S tr a u s and

Rohrbacher^1 8 ^ r e c o r d a m.p. 7 8 .6 -7 9 .2 ° C fo r c i s - 1 : 2 - d i a c e t o x y 1 : 2 : 3 : 4 - t e t r a h y d r on a p h th a le n e . d l - t r a n s - 1 : 2 - d ih y d r o x y -1 : 2 : 3 :4 -te tr a h y d r o n a p h th a le n e . A) .

H y d r o ly s is o f l:2 - d ib r o m o -l: 2 : 3 :4 -t e t r a h y d r o n a p h t h a le n e .

The dibromide was prepared from l: 2 - d ih y d r o n a p h t h a l(15) ene by t h e method o f Bamberger and Lodter • The d i ­ bromide was f i r s t p a r t i a l l y h y d ro ly sed , to y i e l d 1 ( 2 ) b r o m o - 2 ( l) -h y d r o x y -l: 2 : 3 : 4 - t e tr a h y d r o n a p h t h a le n e which was th e n h y d r o ly se d to d l - t r a n s - 1 « 2 - d ih y d r o x y -1 : 2 : 3 ;4 - 1 e t r a ■, n (IS ) hydronaphthalene v

B ).

O x id a tio n n f 1 , 2 -d ih yd r onapbthalene w ith hydrogen p e r (19 ) o x id e i n nresenoe of selenium d io x id e ( o f . S egain The hydrogen peroxide r ea g e n t was prepared a s

d e s c r i b e d above and c o n c e n tr a te d to the d e s i r e d s t r e n g t h by d i s t i l l a t i o n under reduced p r e ssu r e a t room tem p erature i n an a l l g l a s s ap p a ra tu s.

1*2-D ihydronaphthalene (2 g . ) w a s

t r e a t e d w ith an equim olecular p r o p o r tio n o f hydrogen p e r ­ o x id e ( 0 . 5 2 g . i n

~ 2 c c . te r tia r y b u ty l a lc o h o l).

To

t h i s s o l u t i o n , c o o le d to 0 C, was added a s o l u t i o n o f s e le n iu m d io x id e ( 0 .0 6 g . ) i n the minimum q u a n t it y o f t e r ­ t ia r y b u ty l a lc o h o l.

The s o l u t i o n , a f t e r sta n d in g f o r e i g h t

d a y s , y i e l d e d on c o n c e n tr a tio n a deep red , o i l y m a t e r i a l . The s o l i d o b ta in e d by t r e a t i n g t h i s o i l w ith a l i t t l e benzene was s l i g h t l y purple i n c o lo u r and by r e p e a te d c r y s t a l ­ l i s a t i o n from benzene was ob tain ed as c o l o u r l e s s n e e d l e s , m .p . 112°C .

I t d id not depress th e m e ltin g p o in t o f th e

d i o l o b ta in e d by method A) above.

Y ie ld , 0 .4 1 g . ( 1 6 $ ) .

d l - t r a n s - 1 8 2 - d i a e e t o x y - l : 2 : 3 : 4 - te tr a h y d r o n a p h th a le n e . d l - t r a n s - 1 t 2- d ih y d r o x y -1 : 2 j 3 j 4 - 1 et rahydr onaphthal ene was a c e t y l a t e d w ith a c e t i c anhydride i n p y r id in e i n th e u s u a l manner.

The d i a c e t a t e was c r y s t a l l i s e d from p etroleu m ( 18) e t h e r ( 6 0 ~ 8 0 ° 0 ) , m.p. 84°G. S tr a u s and Rohrbacher re­

c o rd a m e lt in g p o in t o f 84°0 f o r t r a n s - 1 : 2 - d i a c e t o x v - l s 2 i 3 i 4 te tr a h y d r o n a p h th a le n e . Rate o f o x id a t io n o f o i s - and t r a n s - 1 : 2 - d ih y d r o x y -1 82 : 3 :4te tr a h y d ro n a p h th a len e w ith le a d t e t r a - a c e t a t e . Lead t e t r a - a c e t a t e was prepared by th e method o f

Dimroth and Sdhw eizer

{ 33)

.

I t was d r ie d over c o n c e n tr a t e d

su.lphu.ric a c id and a s o l u t i o n o f app roxim ately th e d e s i r e d s t r e n g t h prepared by w eighing th e dry m a t e r ia l r a p i d l y and d i s s o l v i n g i t i n a c e t i c a c id d i s t i l l e d over chromium t r i o x id e .

S h is s o l u t i o n was sta n d a r d ise d by t i t r a t i o n w ith

sta n d a rd sodium t h i o s u l p h a t e . D e te r m in a tio n o f th e r a te o f o x i d a t i o n . A known w eigh t o f the d i o l ( ^

0*25 m o le s .) was

d i s s o l v e d i n 10 c c . o f a c e t ic a c id ( d i s t i l l e d over chromium tr io x id e ).

These s o l u t i o n s were m ain tain ed a t a c o n sta n t

tem perature by immersion i n a w ater b a t h .

To each o f th e

s o l u t i o n s 10 c c . o f 0 .1 1 2 If le a d t e t r a - a c e t a t e was r a p i d l y added w i t h s w i r l i n g , th e tim e o f a d d itio n b e in g n o t e d .

A

f l a s k c o n t a i n i n g 10 c c . a c e t i c a c id ( d i s t i l l e d over chromium t r i o x id e ) was t r e a t e d i n th e same way in order to o b t a in a measure o f th e r a te o f consumption o f le a d t e t r a - a c e t a t e i n t h e absence o f d i o l . m ix in g , a l i q u o t s o f 1

g o

At i n t e r v a l s from th e tim e o f . .

were v/ithdrawn, run i n t o a

p o ta ssiu m io d id e-so d iu m a c e t a t e b u f f e r s o l u t i o n and th e i o d i n e l i b e r a t e d t i t r a t e d a g a in s t standard sodium t h io s u lp h a te.

In t h i s way a measure o f th e amount o f l e a d t e t r a ­

a c e t a t e consumed at any s t a g e o f th e o x id a t io n was o b ta in e d . Thus i t was found th a t at 2 0 -2 1°0 and w ith a d i o l

c o n c e n t r a t i o n o f 0*0125 gm. m o l e s / l i t r e th e c i s - d i o l i s com­ p l e t e l y o x i d i s e d a f t e r 30 m in u tes, w h ile th e t r a n s - d i o l i s o n l y o x i d i s e d to th e e x t e n t o f 95)c a f t e r 90 m in u te s . S i m i l a r l y a t 17°0 and a d i o l c o n c e n tr a t io n o f 0 .0 0 3 gm. m o l e s / l i t r e the c i s - d i o l i s c o m p le te ly o x i d i s e d a f t e r 40 m in u te s, whereas the t r a n s - d i o l i s o n ly 80j£ o x i d i s e d a f t e r 180 m in u te s. These r e s u l t s , which are i l l u s t r a t e d g r a p h i c a l l y ( f5' ^

(20 i

m J ? i g . l , j a r e i n agreement w ith th o se o f C r ieg e e T e s t s w ith p otassiu m t r i a c e t y l o sm ia t e .

.

(See page 103 ) .

M o n o -e s te r ific a tio n o f d l- tra n s-1 :2 -d ih y d ro x y -1 ;2 { 3 :4 - t e t r a hyd ron aph thalene w ith 1-m en thoxyacetyl c h l o r i d e . d l - t r a n s - d i o l (1 .9 9 g . ;

1 mole) was d i s s o l v e d i n

dry p y r id in e (40 c c . ) and t r e a t e d w it h f r e s h l y d i s t i l l e d 1 -m en th o x y a o e ty l c h lo r id e ( 2 .8 g . ;

1 m o le ) .

The s o l u t i o n

a f t e r sta n d in g ov ern igh t was poured i n t o water and th e o i l which se p a r a te d e x tr a c t e d w ith e th e r .

The e th e r s o l u t i o n

was th o r o u g h ly washed w ith d i l u t e h y d r o c h lo r ic a c id , d i l u t e sodium hyd roxid e and w ater;

d ried over anhydrous sodium

s u lp h a te and c o n c e n tr a te d .

A y e llo w v i s c o u s o i l was o b ta in e d

w hich s o l i d i f i e d on rubbing w ith petroleum e th e r ( 6 0 - 8 0 ° ) . An a ttem p ted f r a c t i o n a t i o n

oj.

t h i s s o l i d by c r y s t a l l i s a t i o n

from p e tro le u m eth er showed th e p resen ce o f unchanged d i o l

which c o u ld n o t r e a d i l y he removed c o m p le te ly from th e e s t e r . A sample o f th e d i o l was t h e r e f o r e t r e a t e d w ith 1 . 4 e q u i­ v a l e n t s o f m en th o xya cetyl c h lo r id e i n p y r id in e and t h e p ro d u ct i s o l a t e d as above.

C r y s t a l l i s a t i o n from petroleum

e t h e r y i e l d e d a f r a c t i o n o f m.p. 12 2°C .,

M

j

- 6 8 .1 and

f r a c t i o n s o f unchanged d i o l . D i - e s t e r i f i c a t i o n o f d l - t r a n s - 1 : 2 - d ih y d r o x y -1 :2 { 3 : 4 - t e t r a hyd ron aph thalene w ith 1-m en thoxyacetyl c h l o r i d e . d l - t r a n s - 1 :2 ? dihydro xy- 1 : 2 : 3 s 4 - 1 etrahydronapht h a lene ( 2 . 1 g . ) and m ono-ester (4 g . ) ware d i s s o l v e d i n p y r id in e (80 c c . )

and t r e a t e d w ith f r e s h l y d i s t i l l e d 1-m enthoxy­

a c e t y l c h l o r i d e ( 1 1 .7 g . ;

2 .5 moles per mole o f d i o l and

1*5 m o les p er mole o f m o n e - e s t e r ) .

A fte r sta n d in g f o r 60

hou rs th e s o l u t i o n was worked up i n th e usual way, y i e l d i n g 1 0 .3 g . o f s o l i d .

By f r a c t i o n a l c r y s t a l l i s a t i o n o f t h i s

s o l i d from petroleum eth er th e r e wea® o b ta in ed two pure compounds:form) . G, 7 3 .4 ;

(A) m.p. 116-117°C

IPound:

C, 73*6;

H, 9*3$.

( c , 1 i n c h lo r o fo r m ).

I

H, 9 . 2 $ .

- 22. 0° (c , 1 in ch lo ro ­ ^34-^52^6 r e 9.ai r e S

And (B) m .p. 100-101°G i?ound:

O H O r e q u ir e s 0 , 7 3 .4 ; 34 52 6 *

0, 7 3 .4 ;

H, 9 .3

H, 9 .3 ^ .

S a p o n i f l o a t i o n v a la e o f t he e s t e r (A ). The e s t e r (A) (0 .9 6 7 9 g .) was r e f l u x e d w ith

- 1 7 0 .0 °

0 .4 0 9 5 3J m©thanolio potassium hydroxide (11 hours.

go . )

f o r th r e e

The a d d it io n o f a few drops o f w ater a f t e r t h i s

tim e cau sed no p r e c i p i t a t i o n , and e s t e r i f i c a t i o n was t h e r e ­ f o r e assumed to be com p lete.

One drop o f m ethyl red Y/as

added and th e s o l u t i o n t i t r a t e d w ith a standard hydro­ c h l o r i c a c id s o l u t i o n .

1 2 .6 5 c c . o f 0*0837 U h y d r o c h lo r ic

a c i d were r e q u ir e d f o r n e u t r a l i s a t i o n , so t h a t 8 .4 1 cc o f 0 .4 0 9 5 U potassiu m hydroxide were used up i n the h y d r o l y s i s o f th e e s t e r .

This corresponds to 0 .95 81 g . o f d i - e s t e r

and th e compound (A) must t h e r e f o r e be 98.8^ d i - e s t e r : 1 . e . , pure d i - e s t e r w ith in th e l i m i t s o f e x p e rim en ta l e r r o r . R e s o l u t i o n o f d l - t r a n s - 1 ? 2 - d ih y d r o x y -1 : 2 ; 3 i 4 - t e tr a h y d r o ­ n a p h t h a le n e . M ono-ester (2 0 .5 g . ;

1 mole) was d i s s o l v e d i n dry

p y r i d i n e (100 c c . ) and t r e a t e d w ith f r e s h l y d i s t i l l e d _1-monthoxyacetyl c h lo r id e (2 4 .9 g . ;

1 .8 m o l e s ) .

The

s o l u t i o n was c o o le d during th e a d d it io n o f th e a c id c h l o r i d e w hich was accompanied by th e p r e c i p i t a t i o n o f a s o l i d and t h e p r o d u c tio n o f a deep orange c o lo u r .

A fte r s t a n d in g at

room tem p era tu re fo r 40 hours th e s o l u t i o n was worked up i n t h e u s u a l way*

The product (2 7 .2 g .) was an o i l y s o l i d ,

deep r e d i n c o lo u r -

By r e f l u x i n g t h i s s o l i d i n petroleum

e t h e r w it h animal charcoal and r e c r y s t a l l i s i n g th e product

t w i c e from p etro leu m eth er 1 6 .6 g . o f alm ost c o l o u r l e s s s o l i d were o b t a i n e d .

Repeated c r y s t a l l i s a t i o n from petroleum

e t h e r y i e l d e d a l e s s s o l u b l e f r a c t i o n , m .p. 116-117°C .

O ']* - 2 1 ° (G, 1 i n chloroform ) and a more s o l u b l e f r a c t i o n , m.p# 101-102°G

O

- 170° (G, 1 i n c h lo r o fo r m ).

1 - t r a n s - l ; 2 - d ih ydroxy-1 ; 2 : 3 :4 -te tr a h y d r o n a p h th a le n e . The e s t e r o f

M y -21 ° (6 .8 9 g . ) was r e f lu x e d f o r

t h r e e h ou rs w ith 2 .5 $ m ethanolic potassium hydroxide (76 c c . ) . The m ethanol was removed &y d i s t i l l a t i o n and th e r e s id u e e x t r a c t e d w ith e t h e r . d ilu te a lk a li,

The e th e r e x t r a c t was washed w ith

d r ie d over anhydrous sodium s u lp h a te and

c o n c e n t r a t e d , y i e l d i n g 1 .6 1 g . d i o l ( 8 5 $ ) .

The d i o l was

o p t i c a l l y pure a f t e r two c r y s t a l l i s a t i o n s from ben zen e, m .p. 114-115°C bounds

G, 7 3 .4 ;

- 1 2 4 .0 ° (0 , 1 i n chloroform ) . E, 7 . 4 $ .

Gio % 2°2 r e q u ir e s G, 7 3 .2 ;

H, 7 . 3 $ . 1 (+) - t r a n s - 1 : 2 - di ac e t o x y - 1 : 2 :3 ;4 -1 e tr a h y d r o n a p h th a le n e . 1 - t r a n s - l ; 2 - d ih y d ro x y -1 : 2 :3 j 4 - tetra h y d ro n a p h th a len e

(213 mg.) was d i s s o l v e d i n dry p y r id in e (4 c c . ) anhydride (1 c c . ) added w ith c o o l i n g .

and a c e t i c

A fte r sta n d in g

o v e r n ig h t a t room temperature the s o l u t i o n was poured i n t o a m ix tu r e o f d i l u t e su lp h u ric acid and i c e .

The o i l t h a t

s e p a r a te d r a p i d l y s o l i d i f i e d and was f i l t e r e d and d r i e d .

I t was p u r i f i e d by two c r y s t a l l i s a t i o n s from petroleum e th e r (

> 1 2 0 ° C ) , m.p* 6 6 -6 7 °

i ’ound:

G, 67*8;

[o(]?

H, 6 .3 $ .

126° ( 0 , 1 i n c h lo r o fo r m ),

C14H1604 r e q u ir e s C, 6 7 .7 ;

H, 6 . 4 $ . d - t r a n s - l: 2 - d ih y d r o x y - l; 2 s 3 : 4 - t e t r a h y d r o n a g h t h a l e 3 i e . fhe e s t e r o f

-1 7 0 ° ( 6 .3 6 g . ) was r e f l u x e d

\p (\

f o r t h r e e hou rs w ith 2 .5 $ m eth anolic potassium hyd roxid e (7 0 c c . ) .

By working up i n th e same manner as abotfe th e r e

was o b ta in e d 1 .5 5 g . (83$) d i o l , which was p u r i f i e d by two c r y s t a l l i s a t i o n s from benzene, m .p. 114-115°0 (G, 1 i n chloroform )

132°

64° (G, 0 . 5 i n e th a n o l)

[°(\

44° (G, 0 .5 i n e th a n o l. j?ound:

C,

7 3 .2 ;

H, 7 . 1 $ .

gio H12°2

r e ^ r e s C, 7 3 .2 ;

H, 7 . 3 $ . Mixed m .p .

o f d- and 1 -iso m e r s, 104-108°G .

Ihe m elt was

a llo w e d to

r e - s o l i d i f y and i t s m e ltin g p o in t r ed eter m in e d .

I t was th e n found to m elt a t 112°Q, i ^ e . , th e m e l t i n g p o in t of th e d l - d io l . d( - )

- t r a n

s - 1

; 2 - d i a c e t o x y - l s 2 ;3 ;4 -t e tr a h y d r o n a p h th a le n e .

d - t r a n s - 1 t S - d ih y d r o s y - l : 2 :3 :4 -te tr a h y d r o n a p h th a le n e (198 mg.) was d i s s o l v e d i n dry p y r id in e (4 c c . ) and t r e a t e d w i t h a c e t i c anhydride (1 o o . ) .

On working up as i n th e

above c a s e th e re was obtained 284 mg. o f d i a c e t a t e which

8a. was p u r i f i e d by two c r y s t a l l i s a t i o n s from petroleum e th e r ( > 1 2 0 ° C ) , m .p. 66-67°C .

fcO * -f2 5 ° ( 0 , 1 i n chloroform ) .

Mixed m .p . o f th e two d ia o e t a t e s 40-42°C . bounds

0 , 6 7 .7 ;

H, 6.3^

H, 6 •■4$. Goffparison o f th e d e x tr o r o ta to r y dihydro m eta b o lic n a p h th a l­ ene d i o l w ith the s y n t h e t ic d i o l s o b ta in ed above. A sample o f th e dihydrlda o f the m e ta b o lic product was k i n d l y s u p p lie d by P r o fe s s o r Young.

A sample o f the

d i a c e t a t e was prepared from i t by treatm ent w ith a c e t i c anhydride i n p y r i d i n e . f h e i d e n t i t y o f th e di hydro m e t a b o lit e w ith d - t r a n s ­ i t - d i h y d r o x y - 1 s 2 j3 ;4 -tetr a h y d ro n a p h th a len e i s shown i n th e fo llo w in g ta b le;

m .p. °C Dihydro m e t a b o lit e

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