Elenco de tesis

LXX! R = ne^ clou b le bond C, t o Ccj.

7XXIT R = Me, " " C, to IXXÏÏÏ R = H , " " C, t o

LXX

I am m o st g r a t e f u l t o Tt'*, Wood f o r h i s p e r m is s io n t o r e f e r t o t h e s e r e s u l t s in o r d e r to make t h e a c c o u n t c o m p le te .

"" 89 —

s t r u c t u r e o f 0- m e th y lp s y c h o trin e v^ould be r e p r e s e n t e d by

(UQCI) , Hov/everi r e c e n t work (39) upon th e a b s o r p t i o n s p e c t r a o f s u b s tim c e s o f t h e ty p e (liXXIV, R » H o r CgKg) h a s /O cHrR ch- r LXXIV Ixxv shown t h a t t h e y e x i s t i n t h i s fo rm , and n o t a s th e a l t e r n a t i v e s t r u c t u r e (LXXV, R a H o r C6H5) , even th o u g h t h e d o u b le bond

i n (LXX.V) when R = C6H5 , would be c o n ju g a te d w ith two b en z en e

n u c l e i . Thus t h e r e m ust be a s tr o n g te n d e n c y f o r t h e d o u b le bond t o b e e n d o c y c lic a s in (liXXIV), and i t seems m ost

p r o b a b le t h a t t h i s i s a ls o th e c a s e f o r 0- m e t h y l p s y c h o t r i n e ,

I t s s t r u c t u r e can t h e r e f o r e be r e p r e s e n t e d b y (LXXII) , and

th e c l o s e l y r e l a t e d p s y c h o tr in e b y (L X X III), The u l t r a - v i o l e t a b s o r p tio n sp e c tru m o f 0-m e th y lp s y c h o trin e w i l l have t o be

s t u d i e d b e f o r e th e s e m ost p ro b a b le s t r u c t u r e s (L»XX1I) and (WkXIII) c a n b e f i r m l y e s t a b l i s h e d .

The u l t r a v i o l e t a b s o r p tio n s p e c t r a o f some o f t h e e m e tin e d e r i v a t i v e s w hich have b e e n m en tio n ed i n t h i s T h e s is were m easu red b y D r, A ,E , G illa m , t o whom t h e a u th o r e x p r e s s e s h i s s i n c e r e t h a n k s . The i n t e r p r e t a t i o n s o f t h e r e s u l t s

c o l l e c t e d h e r e were g iv e n in th e d i s c u s s i o n s o f th e s u b s t a n c e s , and n eed n o t be r e p e a t e d .

— 90 —

COBPQUBfl. > f

De s-N (a ) - em et in e te tra h y d ro m e t h i n e 2666 1 5 ,9 0 0 m e th io d id e (aXVXI1,X* = I " ) 3030"" 7 ,2 4 0

Dee-N( a )-e rn e tin e h e x a h y d ro m e th in e (XLI) 2840 6 ,9 0 0 D e s-N (a )-e rn e tin e h e x a h y d ro M sm e th in e ()iLIV) 2660 1 2 ,6 0 0 3030^ 3 ,6 6 0 Ileutr^ü. m a t t e r (XLV) from Hofmann

d e iir a d a tio n o f d e s-N (a )-e ra e tln e h e x a h y d ro ~ 2656 1 6 ,1 0 0

me t h i n e m e th io d id e . 3040^ 6 ,1 6 0

F i n a l d o u b ly u n s a t u r a te d n e u t r a l p r o d u c t (LX) 2280 2 4 ,8 0 0 2910 1 9 ,1 0 0 ^ Inflexion

SYNTHETICAL INVESTIG^iTlOND.

I n t h e a u t h o r ’ s e a r l y w ork, a tte c q ^ ts w ere made t o s y n t h e s i s e t h e sti* u c tu re (LXXVI) by v a r io u s r o u t e s , and t h i s work was c o n tin u e d i n th e p r e s e n t r e s e a r c h e s . The s t r u c t u r e

(LXXVI) can b e s e e n t o be th e m ain s k e le to n o f B r in d le y and

NH

CO

CxxvT _IXXVII

Pyman* 8 p r o p o s a l (XVII p . 35) f o r e m e tin e , and i t was th o u g h t

t h a t a s y n t h e s i s o f (LXXVI) c o u ld b e m o d ifie d t o g iv e e m e tin e i t s e l f , sh o u ld (XVII) prove t o b e c o r r e c t . A c o m p a riso n o f th e p r o p e r t i e s o f (LI\XVI) w ith t h o s e o f e m e tin e , and t h e p o s s i b i l i t y o f s tu d y in g i t s o x id a tio n by m e rc u ric a c e t a t e .

- 91 -

w ere a l s o f a c t o r s w hich prom pted th e s t a r t o f t h e s y n t h e s i s . i l f t e r two r o u t e s to (LXXVI) h ad b e e n i n v e s t i g a t e d and abandoned ( 4 0 ) , a m ost p ro m is in g one was f o u n d . I t was b a s e d upon t h e p r e p a r a t i o n o f m e th v l p e n ta n e - l i 3 ; 5 »

t r i c a r b o x v l a t e (LXXVIII) as t h e key s u b s t a n c e , M alo n ic e s t e r was co n d en sed w ith form aldehyde >mô. th e r e s u l t i n g e t h v l p e n ta n e . 181 :3 ; 3 ; 5 Î arl?9XYlat,e, y ie ld e d n e n ta n e - 113 : 5 - t r i e a r b o x v l i e a c id on h y d r o l y s i s and d e c a r b o x y la tio n , t h i s a c i d b e in g e s t e r i f i e d t o p iv e (LXXVIII) (41) , co^Me LXXVIII LXXIX

I t W a s e n v isa g e d t h a t th e tv/o p r im a r y c AirbornetJioxyl

g ro u p s i n (LXXVIII) would r e a c t more r e a d i l y w ith

/^ -p h e n y le th y la m in e th a n would t h e s e c o n d a ry g r o u p . The t r i - e s t e r was t h e r e f o r e h e a te d i n t e t r a l i n , and two m o le c u la r p r o p o r t i o n s o f th e amine dropped i n g r a d u a l l y o v e r many h o u r s ; i n t h i s way I no a p p r e c ia b le c o n c e n t r a t i o n o f u n r e a c t e d amine was p r e s e n t a t any tim e . From t h e r e a c t i o n p r o d u c t , t h e

d iam id e (LXXIX) was i s o l a t e d i n t h e c r y s t a l l i n e s t a t e , t o g e t h e r w ith s m a lle r q u a n t i t i e s o f th e mono- and t r i - a m i d e s , a ls o

c r y s t a l l i n e .

- 92 -

The d i amide was to h av e been s u b je c te d t o t h e

B is c h le r* -L Ia p ie ra ls k i r e a c t i o n t o b r i n g a b o u t r i n g c l o s u r e t o t h e b i s - 3 8 4 -d ih y d ro is Q .u in o lin e (LkXX), w hich on r e d u c t i o n was e x p e c te d t o y i e l d (LXXVII), The l a s t s t a g e i n t h e s y n t h e s i s , t h e r e d u c t i o n o f t h e la c ta m (LXXVII) t o (LXXVI), i s one Which ca n b e b r o u g h t a b o u t v e ry r e a d i l y by l i t h i u m alum inium h y d r id e

( 4 2 ) . H ow ever, b e f o r e th e r i n g c lo s u r e o f t h e d ijy aid o h a d b e e n f u l l y i n v e s t i g a t e d , th e B r in d le y and Pyman p r o p o s a l f o r

t h e s t r u c t u r e o f em etin e was shown t o be i n c o r r e c t , and a s a r e s u l t , t h i s s y n t h e t i c work was d i s c o n tin u e d .

CEîiBRAL IKFOBiaTION

*

Ilo te 1 . A n a ly se s m arked were c a n 'i e d o u t b y î.tr. D .J . L lo y d and H is s A. D o h e rty , o f H anches t e r

U n i v e r s i t y ; and t h e re m a in d e r b y D r s . W e ile r and S t r a u s s , O x fo rd .

Ilo te 2 . A l l s o l i d s were d r i e d i n vacuo a t room te m p e r a tu r e o v e r p h o s p h o ric o x id e , u n l e s s o th e r w is e s t a t e d . N ote 3 . S o lu tio n s o f p r o d u c ts in e t h e r o r c h lo ro fo rm w ere

d r i e d w ith sodium s u l p h a t e , u n l e s s o th e r w is e s t a t e d •

— 93

(V) E^CFERII^iTAL SECTIQH.

Preparation of . -methvleiMtlnemathlne dlmethiodldfl

(XXXV) .

The m eth in e (:\XIV) ( 1 .3 3 g . ) was d i s s o l v e d In

an h y d ro u s a l k a l i - f l ^ e e t h e r ( 1 2 c . c . ) and t r e a t é d w ith e x c e s s

o f d ry m e th y l io d id e (1 .5 c . c * ) . A f t e r 24 l i r a , a t room

te m p e r a tu r e , th e amorphous p r e c i p i t a t e was c o l l e c t e d and w ashed w ith an h y d ro u s e t h e r , (1 .7 3 g*) m .p . 132-135® , w ith

e f f e r v e s c e n c e , a f t e r s i n t e r i n g from 110®. A seco n d c ro p

( 8 6 mg*) was o b ta in e d by adding m e th y l io d id e ( 2 c . c . ) t o t h e

f i l t r a t e , and a llo w in g to s ta n d f o r a f u r t h e r 84 h r s . ; o n ly 42 mg. o f r e s i d u e rem ained when t h e f i n a l f i l t r a t e was

e v a p o r a te d .

A p o r t i o n o f th e f i r s t c ro p (1 .0 7 2 g . ) was d i s s o l v e d i n e th y le n e d i c h l o r i d e ( 4 c . c . ) and allo w ed t o s t a n d .

C r y s t a l l i s a t i o n o c c u rre d a f t e r s c r a t c h i n g , and t h e s o l i d

(0 .3 6 6 g . ) was washed w ith e th y le n e d i c h l o r i d e , m .p . 137-138® d e c . w ith e f f e r v e s c e n c e ; th e c r y s t a l s were s e e n t o be

t r a p e z o i d a l p ris m s u n d e r th e m ic ro s c o p e . On r e c r y s t a l l i s a t i o n tw ic e from a c e to n e , th e m .p. o f t h e c o l o u r l e s s , s h o r t p r is m s

so o b t a i n e d , was 151-153®, a f t e r s l i g h t p r e v io u s s i n t e r i n g , t o a c l e a r m e lt w hich soon became c lo u d y . The m .p . was

unchanged by a f u r t h e r r e c r y s t a l l i s a t i o n fro m a c e to n e t o g iv e th e a n a l y s i s sp e c im e n , which was d r i e d f o r 2 h r s . i n v acu o a t