N IT R IT E ACTIVATIO N BY ORGANIC ANHYDRIDES

A th e s is su b m itted by N IG EL P E T E R BOTTINGin p a r t ia l fu lfilm en t o f the r e q u ir e m e n ts fo r the d e g r e e o f D octo r of P h ilo so p h y of the U n iv e r s ity of London

O ctob er 1986D ep artm en t of C h e m is tr y Im p er ia l C o lle g e South K en sin g to n London S. W. 7 .

11A B ST R A C T

The r e a c tio n o f n itr ite ion w ith so m e h e ter o cu m u le n e o rg a n ic a n h y d r id es i s in v e s t ig a te d w ith r e fe r e n c e to the a c t iv a t io n of the n itr ite a s a n itr o sa tin g a g e n t.

N itr ite io n r e a c ts w ith a r o m a tic iso c y a n a te s in o rg a n ic s o lv e n ts to g iv e good y ie ld s o f 1 , 3 -d ia r y l t r ia z e n e s . R ea c tio n o c c u r s v ia n u c le o p h ilic a tta ck of n itr ite ion on the iso c y a n a te , and r e a r r a n g e m e n t of the in te r m e d ia te to g iv e an N -n it r o s o s p e c ie s . L o s s o f ca rb o n d io x id e g iv e s an a r o m a tic d ia z o ta te w h ich r e a c ts w ith fu r th er is o c y a n a te to y ie ld the 1 , 3 -d ia r y ltr ia z e n e . In d ep en d en t r e a c t io n of the is o la te d d ia z o ta te is d em o n s tr a te d .

A lk y l is o c y a n a te s w ere l e s s r e a c t iv e . R ea c tio n w ith n itr ite io n in th e p r e s e n c e of d ib u ty l tin d ia c e ta te , a L ew is a c id , g iv e s d ea m in a tio n p r o d u c ts .

A ro m a tic c a r b o d iim id e s r e a c t a n a lo g o u sly g iv in g d ia z o ta te s and h en ce 1 ,3 - d ia r y l t r ia z e n e s . F o r u n s y m m e tr ic a l c a r b o d iim id e s the s e le c t iv i t y of the n itr o sa t io n is d is c u s s e d .

Iso th io c y a n a te s gave on ly s m a ll am ou n ts of n itr o s a t io n . E v id en c e in d ica ted that S -n itr o s a t io n p r e d o m in a te s .

The r e a c t io n s p ro v id e a n o v e l rou te to n itr o s a t io n p ro d u cts fr o m n itr ite ion under m ild n o n -a c id ic c o n d it io n s .

Ill

CO NTENTSP a g e

1. In trod u ction and R ev iew I1 .1 In trod u ctio n 21 .2 N itr o sa t io n under N o n -a c id ic C on dition s 3

1 .2 .1 N itr o sa t io n by A lk y l N itr ite s 31 .2 .2 N itr o sa t io n by G a se o u s N itro g en O x id es 41 .2 .3 N itr o sa t io n by T r a n s it io n -M e ta l 6

N itr o s y l C o m p le x e s .1 .3 N itr ite A c t iv a t io n 8

1 .3 .1 P h o to ly s is 81 .3 .2 R a d io ly s is 81 .3 .3 R e a c tio n w ith A c e t ic A nh yd rid e 91 .3 .4 R e a c tio n w ith Im in iu m C ations 11

1 .4 The R e a c t io n of H e te r o c u m u le n e s 151 .4 .1 I so c y a n a te s 151 .4 .2 I so th io c y a n a te s 201 .4 .3 C a r b o d iim id e s 221 .4 .4 N -S u lp h in y la m in es 25

1 .5 C o n c lu s io n 272. R ea c tio n of N itr ite Ion w ith A r o m a tic I so c y a n a te s 28

2 . 1 In trod u ctio n 292 . 2 H e te r o g e n e o u s R ea c tio n 292 .3 R ea c tio n u n d er A q u eou s C on d ition s 312 .4 R ea c tio n o f P h en y l I so c y a n a te in O rgan ic S o lv e n ts 31

2 .4 .1 T o lu en e 312 .4 .2 A c e to n itr i le 32

2 . 5 R ea c tio n of 4 -N itr o p h e n y l Iso cy a n a te in A c e to n itr i le 332. 6 E v id en ce fo r P r o p o se d M ech a n ism 36

2. 6. 1 E v o lu tio n of C arb on D io x id e 362. 6. 2 D e te c t io n of the D ia z o ta te 362. 6. 3 R e a c t io n of D ia z o ta te w ith Iso cy a n a te 37

IV

P a Se2 .7 V a r ia tio n of S o lv en t 38

2 .7 .1 T e tra h y d ro fu ra n 382 .7 . 2 D im e th y l S u lphoxide 38

2 .8 V a r ia tio n o f Iso c y a n a te S tru ctu re 402. 8. 1 P h e n y l Iso cy a n a te 402 .8 .2 O ther 4 -S u b stitu ted P h en y l I so c y a n a te s 412 .8 .3 E ffe c t of S u b stitu en ts 42

2 .9 C o n c lu s io n 433. R ea c tio n of N itr ite Ion w ith A lk y l I so c y a n a te s 46

3. 1 In trod u ctio n 473 .2 C on su m p tion of N itr ite 473 .3 C a ta ly s is by D ib u ty l T in D ia c e ta te 473 .4 P ro d u c t A n a ly s is in DMSO 533 .5 P ro d u c t A n a ly s is in A c e to n itr ile 543 .6 M ech a n ism of R ea c tio n 593 .7 K in e t ic s of nP r o p y l and B utyl Iso cy a n a te 64

n t3 .8 P ro d u c t A n a ly s is fo r P r o p y l and B utylIso c y a n a te 70

3 .9 C o n c lu s io n 734 . R ea c tio n of N itr ite Ion w ith C a rb o d iim id es 74

4 . 1 In trod u ctio n 754 .2 C h o ice o f S u b stra te 754 .3 F o r m a tio n of T r ia z e n e 754 .4 R ea c tio n M ech a n ism 764 .5 S e le c t iv ity of N itr o sa t io n 804 .6 R ea c tio n of D ip h en y l C a rb o d iim id e 814 .7 C o n c lu s io n 83

5 . R ea c tio n of N itr ite Ion w ith A r o m a tic Iso th io c y a n a te s 855 . 1 In trod u ctio n 865 .2 T r ia zen e F o r m a tio n fr o m 4 -N itr o p h e n y liso th io c y a n a te 875 .3 D ia z o ta te F o r m a tio n 905 .4 R ea c tio n of P h en y l Iso th io cy a n a te 91

P a g e919192959599

104108112

111

125126

127127127132132136137138138141144146148149149149150150152152153

v

5 .4 . 1 Y ie ld s of T r ia z e n e5 . 4 . 2 Y ie ld s of D ia zo ta te

5 .5 K in e t ic s o f R ea c tio n of P h en y l Iso th io cy a n a te5 .6 S p e c tr a l B eh a v io u r of R ea c tio n P ro d u c ts5 .7 P r o p o s e d M ech a n ism5 .8 I so la t io n and T rapping of P ro d u c ts5.9 Further Spectral Behaviour

5. 10 I s o c y a n a te s a s R ea c tio n P ro d u c ts5 .1 1 E v id en c e fr o m I. R . and N. M. R. S p e c tr o sc o p y5 .1 2 O ther 4 -S u b stitu ted P h e n y l I so th io c y a n a tes5. 13 C on clu d in g R em a rk s

6. R ea ctio n of N itr ite Ion w ith A lk y l I so th io c y a n a tes6. 1 In tro d u ctio n6 .2 C o n su m p tion of N itr ite6. 3 K in e t ic s of R ea ctio n6 .4 P r o d u c t A n a ly s is6. 5 P r o p o s e d R ea c tio n M ech a n ism6. 6 C on clu d in g R em a rk s

7 . R ea ctio n of N itr ite Ion w ith N -S u lp h in y ia m in es7. 1 In tro d u ctio n7 .2 R e a c tio n of N -S u lp h in y l-4 -N itr o a n ilin e7 .3 R e a c tio n o f N -S u lp h in y la n ilin e7 .4 C on clu d in g R em a rk s

8 . C o n c lu s io n s9 . E x p e r im e n ta l

9 . 1 G e n e r a l and In stru m en ta tion9 .2 A r o m a t ic Iso c y a n a te s

9 .2 .1 H e te r o g e n o u s R ea c tio n9 . 2 . 2 R e a c tio n in A q u eo u s S olution9. 2. 3 R e a c tio n in T o lu en e9 . 2 . 4 P r e p a r a tio n of 1, 3 -D ip h e n y ltr ia z e n e9 .2 . 5 P r e p a r a tio n of T e tra e th y la m m o n iu m N itr ite9 . 2 . 6 R e a c t io n of P h en y l Iso cya n a te in A c e to n itr i le

P a g e9 . 2 . 7 R e a c tio n of 4 -N itr o p h e n y l I so c y a n a te in

A c e to n itr i le 1539 .2 . 8 P r e p a r a tio n of 1 ,3 - b i s (4 -N itr o p h e n y l)

T r ia z e n e 1539. 2 .9 D e te c t io n of C arbon D io x id e 1549 . 2. 10 P r e p a r a tio n of Sod iu m 4 -N itr o p h e n y l D ia z o ta te 1549 .2 . 11 D ia z o ta te D eter m in a tio n 1559. 2. 12 H P L C A n a ly s is of 1 , 3 -D ia r y l T r ia z e n e s 1569 .2 . 13 O p tim iza tio n of T r ia z e n e Y ie ld s 1569 . 2. 14 P r e p a r a tio n of 1 , 3 -D ia r y l T r ia z e n e s 157

9 .3 A lk y l I so c y a n a te s 1599 . 3 . 1 N itr ite C on sum p tion E x p e r im e n ts 1599 . 3 . 2 K in e tic S tu d ies 1599 . 3 . 3 P r o d u c t A n a ly s is 1639 » 3 .4 P r e p a r a tio n of A c e ta te s 165

9 .4 C a r b o d iim id e s 1659 .4 . 1 P r e p a r a t io n of E th y l-4 -N itr o p h e n y l

C a rb o d iim id e 1659 . 4 . 2 P r e p a r a tio n of D ip h e n y lca r b o d iim id e 1669 .4 . 3 M ea su rem en t of T r ia z e n e Y ie ld s 1679 . 4 . 4 I so la t io n of N itr o so u r e a 1679 .4 . 5 N itr o sa t io n of 1-E th y l-3 (4 -N itr o p h e n y l) U rea 168

9 .5 A r o m a t ic Iso th io cy a n a tes 1699 .5 . 1 P r e p a r a tio n of 4 -N itr o p h e n y l Iso th io c y a n a te 1699 . 5 . 2 P r e p a r a tio n of 4 -C h lo r o p h en y l I so th io c y a n a te 170 9 . 5r. 3 P r e p a r a t io n of 4 -M eth o x y p h en y l Iso th io c y a n a te 1709 . 5 . 4 M ea su rem en t of D ia zo ta te and T r ia z e n e Y ie ld s 1709 .5 . 5 K in e tic S tu d ies of P h en y l I so th io c y a n a te 1709 . 5 . 6 T rap p in g E x p er im en ts 175

9 . 5 . 6 . 1 C h lo r o tr im e th y s ila n e 1759 . 5 . 6 . Z D im eth y l Sulphate 175

9 . 5 . 7 A n a ly s is fo r Iso c y a n a te s 1769 . 5 . 7 .1 P h en y l Iso cy a n a te 1769 . 5 . 7. 2 4 -N itr o p h e n y l I so c y a n a te 176

- vi -

VI1

P a g e9 . 5 . 8 N itr ite C on sum p tion E x p e r im e n ts 1779 .5 . 9 K in e t ic s of 4 -S u b s titu te d P h en y l

Iso th io c y a n a te s 1799 .5 . 10 15N N. M. R . S tu d ie s 186

9 .6 A lk y l Iso th io c y a n a te s 1869 .6 . 1 K in e t ic s 1869. 6. 2 A n a ly s is fo r C y c lo h e x y l I so c y a n a te 187

9 .7 N -S u lp h in y l A m in es 1919 .7 . 1 P r e p a r a tio n of N -S u lp h in y l-4 -N itr o a n il in e 1919 . 7 . 2 P r e p a r a tio n of N -S u lp h in y l A n ilin e 1919 . 7 . 3 K in e t ic s 1919 . 7 . 4 H y d r o ly s is R ea c tio n 194

10. R e fe r e n c e s 195

Vlll

A C K N O W LED G EM EN TSF ir s t ly I w ould lik e to thank D r . B r ia n C h a llis fo r h is

e n c o u r a g e m e n t and su p e r v is io n d u r in g the c o u r se of th is p r o je c t . I w ould a ls o lik e to thank the SERC fo r a quota a w a rd .

T hanks go to the te c h n ic a l and a c a d e m ic s ta f f o f Im p er ia l C o lle g e fo r th e ir a s s i s t a n c e , and to the s ta f f o f the d e p a r tm e n ta l m ic r o - a n a ly t ic a l , n . m . r . and m a ss s p e c tr o m e tr y s e r v i c e s . In p a r tic u la rth an ks to D r . J . A . C h a llis fo r run ning the g . c . m . s . , and R . V. S h ep ard, . , 15^Tfo r running the N n .m .r . s p e c tr a .

M any thanks to m y fe llo w stu d en ts in the H arw ood Labfo r p ro v id in g a happy w orkin g a tm o s p h e r e , in p a r t ic u la r T ed , S o t ir is ,A n d y, B en , D o u g g ie , K im , N ir m a l, M ersh id and N e i l .

My g ra titu d e a ls o g o es to Joan n a fo r typ in g th is th e s is so w e lland so q u ick ly .

F in a lly , m an y thanks to m y p a r e n ts fo r th e ir su p p ort and e n c o u r a g e m e n t th rou gh ou t m y t im e at U n iv e r s ity . To th em I d ed ic a te th is t h e s is .

C H A PT E R 1

INTRO DUCTIO N AND R EV IE W

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1. 1 INTRO DUCTIO NC o n s id e r a b le in te r e s t co n tin u es to be show n in the fo r m a tio n of

1 ,2N -n itr o s o com p ou n d s due to th e ir im p lic a t io n in c a n c e r in d u ctio n .Indeed the in v iv o fo r m a tio n of N -n itr o s o com pounds h a s b een p ro p o se d

, , ̂ . 3 ,4to be the c a u se of g a s tr ic c a n c e r .N itr o sa t io n r e a c t io n s a re n o r m a lly c a r r ied out u nd er a c id ic

c o n d it io n s , in the p r e s e n c e of n itro u s a c id . The n itr o u s a c id i s i t s e l fu n r e a c t iv e but i s in e q u ilib r iu m w ith a range of r e a c t iv e s p e c ie s . S om e

, in o rd er of in c r e a s in g r e a c t iv ity .

n itro u s an h yd rid e n itro u s c h lo r id e n itro u s a c id iu m ion n itro u so n iu m ion

SCHEM E 1

a r e l is te d in S ch em e

ON - NOz ON - C l ON - OH* ON*

A ll of th e s e r e a g e n ts a re e le c tr o p h il ic . T hey e f fe c t n itr o sa t io n by d e liv e r in g th e NO* en tity to a su ita b le n u c leo p h ile , su ch a s an a m in o s u b s tr a te .

5 6 7P a s t r e v ie w s ’ ’ fu lly d e s c r ib e the m e c h a n is t ic and k in e ticd e ta i ls o f N -n itr o s a t io n in aqu eou s so lu tio n . M ethods fo r c a r r y in g out n itr o s a t io n r e a c t io n s under n o n -a c id ic con d itio n s a re r e la t iv e ly few . T h ey in c lu d e th e u se of the g a se o u s n itr o g e n o x id es and c e r ta in a lk y l n itr i t e s in a q u eo u s a lk a li so lu tio n .

N itr ite io n i t s e l f cannot b rin g about n itr o sa tio n . H o w ev er , th e re i s so m e c u r r e n t in t e r e s t in m eth od s o f a c tiv a tin g n itr ite a s a n itr o sa t in g a g en t under m ild c o n d it io n s . One ro u te i s by r e a c tio n o f n itr ite ion w ith o r g a n ic a n h y d r id e s . Our w ork c o n c e r n s the rea c tio n of n itr ite w ith the h e te r o c u m u le n e a n h y d r id e s .

T he fo llo w in g r e v ie w c o v e r s m eth o d s fo r n itr o sa t io n u nd er n on - a c id ic c o n d itio n s and r e le v a n t a s p e c ts o f the c h e m is tr y o f th e h e t e r o c u m u len e a n h y d r id es; the is o c y a n a te s , iso th io c y a n a te s , c a r b o d iim id e s and N -su lp h in y l a m in e s .

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1 .2 NITROSATIO N UNDER NO N-ACIDIC CONDITIONS1 .2 .1 N itr o sa tio n by A lk y l N itr ite s

A lk y l n itr ite s (RONO) a r e o ften em p lo y ed a s a s o u r c e o f n itro u s 8a c id . The s im p le a lk y l n itr i te s su ch a s a m y l n itr ite a re n o r m a lly

a c t iv a te d by an acid c a ta ly s t , p ro m o tin g c le a v a g e of the O -N O bond.+ , RNH+ jl

(S ch em e 2)R -O -N O

H3 ° +R O -N O

HROH + R NNO + H O

u 5

SCHEM E 2

H y d r o ly s is u nder a c id ic and n eu tr a l con d itio n s w as found to be9f a s t e r than in aq u eou s a lk a li . C lea v a g e of the O -NO bond w a s

d e m o n str a te d to o ccu r d urin g h y d r o ly s is of o p tic a lly a c t iv e a lk y l n it r i t e s ,. . 1 0w ith r e te n tio n of co n fig u ra tio n .

R ec e n t w ork h as b een c a r r ie d out on the h y d r o ly s is and a m in o ly s is o f ^ -p h e n e th y l n itr ite , by Oae and c o - w o r k e r s . ^ A lk a lin e h y d r o ly s is g a v e the co rresp o n d in g a lc o h o l and w as found to be a c c e le r a te d by t r ie t h y la m in e s . S eco n d a ry a m in e s w e r e n itr o sa te d in a lk a lin e co n d itio n s in q u a n tita tiv e y ie ld . Good k in e t ic b eh a v io u r w as o b se r v e d and the seco n d o r d e r ra te c o n sta n ts w e r e d e te r m in e d .

12The b a se c a ta ly se d h y d r o ly s is w as stu d ied in d e ta il and co m p a red12w ith h y d r o ly s is of c a r b o x y lic e s t e r s . The c a r b o x y lic e s t e r s re a c te d

m o r e r a p id ly . The a lk y l n itr i te s sh ow ed la r g e r p o la r e f fe c t s in the le a v in g a lk o x id e grou p , s m a lle r s t e r ic e f f e c t s , and u n lik e the e s t e r s g a v e no o x y g en ex ch an ge w ith the m ed iu m during h y d r o ly s is . It w as a rg u ed that th e se r e s u lt s im p lie d a c o n c er te d d isp la c e m e n t fo r a lk y l n itr ite h y d r o ly s is (E q u ation 1) ra th er than the a d d it io n -e lim in a tio n m e c h a n is m that h as b een e s ta b lis h e d fo r b a se c a ta ly se d h y d r o ly s is of c a r b o x y lic e s t e r s .

RONO + HO" ------------► RO" + HONO - 1

A s im ila r c o n c e r te d m e c h a n ism w as p ro p o sed fo r r e a c t io n w ith a m in e s u nd er b a s ic co n d itio n s in a q u eou s d ioxan . ^ A s o lv e n t iso to p e e f fe c t (k ^ /k ^ ) of around 2 w as found fo r a m in o ly s is , im p ly in g that p ro to n t r a n s f e r to the a lk o x id e o c c u r s in the r a te - l im it in g s tep . A tr a n s it io n

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sta te w a s p ro p o sed w h ere OH bond fo r m a tio n is sy n ch ro n o u s w ith O -N bond f i s s io n and N -N bond fo r m a tio n (S ch em e 3).

The B r^ n sted p lo ts fo r the a m in o ly s is w er e s c a t te r e d . R ea so n a b le c o r r e la t io n w as obta ined for

R O -N O + R R NH

R

H -------ii

4=

SCH EM E 3

tROH + R R NNO 1 2

a m in e s of s im ila r s tr u c tu r e , g iv in g a p v a lu e of 0. 58 fo r a lip h a ticse c o n d a r y a m in e s . H o w ev er the p o in ts fo r a m m o n ia , and the p r im a r yand te r t ia r y a m in es d ev ia te d fr o m the lin e . A good c o r r e la t io n w asob ta in ed b etw een log k and the v e r t ic a l io n iz a tio n p o te n tia ls of the a m in e s .Ih e lo w er the p o ten tia l th e fa s te r the r e a c tio n .

S im ila r r e s u lt s h ave b een obta ined for the r e a c t io n s ofru'VAVe. 13 14 i

P - ethoxye-feha-n o l, fo r both h y d r o ly s is and a m in o ly s is in a q u eo u s a lk a li.;1 .2 .2 N itr o sa tio n by G a seo u s N itro g en O xides

The n itr o sa tio n o f a m in e s in n eu tra l and a lk a lin e so lu tio n w ithg a se o u s d in itro g en tr io x id e (N _ 0 _ ) and d in itro g en te tr o x id e (N O ) h as

2 3 1617 2 4b een rep o rted by C h a llis and K y rto p o u lo s . *

- 5 -

p red om in a n t a s a n itr o sa t in g agen t in so lu tio n , r e a c tin g w ith th e a m in e on en co u n ter . R a d ic a l cou p lin g to g iv e ONONO^ or the d if fu s io n of N O into the aq u eou s p h a se w ould h ave to be the ra te l im it in g s te p . ACu *

s im ila r m e ch a n ism can be p ro p o sed fo r the r e a c t io n o f N O .P r e p a r a t iv e ly g a s e o u s N O h as b een u sed to p ro d u ce N -n itr o s o

18 1 3 19 com pounds , and to d ea m in a te p r im a r y a m in e s in o rg a n ic s o lv e n t s .

O^N - NO^ ^ NO!> + NO^ gas P^a seJ

s lo w

SCH EM E 4

N itr o sa t io n p ro d u cts h ave a ls o b een is o la te d fr o m r e a c t io n s of N _ 0 in20 21carb on te tr a c h lo r id e . * K in e t ic s o f the d ia z o t is a t io n o f a n ilin e w ith

N O in a c e to n it r i le , e th y l a c e ta te and m ix tu r e s o f th e se s o lv e n t s ,u TC _ ^22h ave b een m e a s u r e d . The r e a c t io n w as f i r s t o r d e r in N .O ,, and z e r oZ 4

o rd e r in a n ilin e , and the ra te l im it in g step w a s p r o p o se d to be fo r m a tio nof the n itro u so n iu m io n (S ch em e 5 ). G a seo u s N O h a s a ls o b ee n u sed

23to p rod u ce N -n itr o s a m id e s by r e a c t io n w ith a m id e s in d ic h lo r o m e th a n eoin the p r e s e n c e of so d iu m a ce ta te a t low te m p e r a tu r e ( -2 0 C ).

P h N H 2

-------------- ► D ia z o t iz a t io n P r o d u c ts lo w

N O 2 4 N 0 3 + NO+

SCH EM E 5

- 6 -

N itr ic ox id e (NO) r e a c ts w ith a m in es to fo r m N -n it r o s a m in e s ,a lthough it a p p ea rs not to be the n itr o sa tin g a g en t. T he p r e s e n c e of a iror o th er c a ta ly s ts w a s r e q u ir e d , and n itr o g e n d io x id e or o th er s p e c ie sw e r e a ssu m e d to b r in g ab ou t r e a c t io n . ^ F o r e x a m p le in the p r e s e n c e

25of io d in e , n itr o s y l io d id e (NOI) w as found to be the n itr o sa t in g a g en t.W ith s i lv e r io n s p r e s e n t it w a s b e lie v e d that the a m in e w a s o x id ise d to

2 6a ca tio n r a d ica l and th is r e a c te d d ir e c t ly w ith the n itr ic o x id e .(S ch em e 6).

24

A g +R 2NH r 2 n h

NOR 2N -N O + H

SCH EM E 6

1 .2 .3 N itr o s a t io n by T r a n s it io n M etal N itr o sy l C o m p le x e sA n um ber o f tr a n s it io n m e ta l n itr o s y l c o m p le x e s h av e b een show n

to a c t a s n itr o sa t in g a g e n ts u nder n o n -a c id ic c o n d it io n s . F o r ex a m p len itr ic oxide fo r m s a c o m p le x w ith cop p er (II) s a l t s . T h is co p p ern itr o s y l c o m p le x w a s a p o w er fu l n itr o sa tin g a g en t in a lk a lin e m e d ia ,and o rg a n ic so lv e n ts g iv in g q u a n tita tiv e y ie ld s o f n itr o s a m in e s fr o m

2 7 ,2 8 .r e a c t io n w ith se c o n d a r y a m in e s . (S ch em e 7).

Cu11 + NO

C u n N O + R 2N H

C u n N O

Cu1 + H+ + R 2NNOSC H E M E 7

The n itr o p r u s s id e an ion (1) n itr o sa te d k e to n es su ch a s a ce to n e2 9 ,3 0and a ce to p h en o n e , u n d er b a s ic c o n d itio n s to p ro d u ce o x im e s .

S im ila r i ly r e a c t io n w ith se c o n d a r y a m in e s gave N -n it r o s a m in e s , and w ith p r im a r y a m in e s d ea m in a tio n p ro d u c ts w er e o b ta in ed . The d ea m in a tio n s cou ld be c a r r ie d out at p H 's up to 12. 7 , a lth o u g h at h ig h e r pH the n itr o p r u ss id e ion i s d e s tr o y e d . D ea m in a tio n p ro d u ced p red o m in a n tly a lc o h o ls w ith s m a ll a m ou n ts of a lk e n e , and in the p r e s e n c e o f a ir , t r a c e s o f o x id is e d p r o d u c ts . F o r ex a m p le c y c lo h e x y la m in e g a v e 120% c y c lo h e x a n o l, 9% c y c lo h e x e n e and 3% c y c lo h e x a n o n e . P red o m in a n t fo r m a tio n o f the a lc o h o l i s e x p e c ted in th e b a s ic c o n d itio n s

- 7 -

em p lo y ed .The m e c h a n is m p r o p o se d (S ch em e 8) in v o lv ed a tta ck of the a m in e

on the n itr o s y l c o m p le x . A ro m a tic a m in es w e r e u n r e a c t iv e , p ro b a b ly b e c a u se of th e ir lo w e r b a s ic it y . The new c o m p le x (2) cou ld th en r e a c t w ith a n o th er m o le c u le o f a m in e to r e le a s e the n itr o s o com pound .

[Fe (C N )5 NO] 2 “ + R N H 2 — ------ — [R N H ^N O Fe (C N )5] 2 '

( 1)

[ r NH ^NO Fe (C N )5 ] 2 " + R N H 2 ------------ ► RNHNO + H + [R N H ^Fe(C N )5] 2

H 2° +RNHNO ------------ ► RNCd

R N 2 + ------------ ► R + -------------- ► PRO DU CTS

SCH EM E 8

A seco n d p o s s ib i l i t y w as lo s s of w a ter fr o m the c o m p le x (2), to g iv e a c o m p lex ed d ia z o n iu m io n (3) w hich th en fr a g m e n ts by r e a c tio n w ith fu r th er a m in e (S c h e m e 9 ).

[RNH N O F e(C N ) ] 2 ' -------------- ^ [R N F e(C N ) ] 2 "

( 2)

2(3)

+ h 2 o

[RN F e(C N ) ] 2 " + RNH RN + + [RNH F e(C N ) ]

S C H E M E 9

N itr o sa t io n h a s a ls o b een o b se r v e d fr o m ru th en iu m n itr o s y l 32c o m p le x e s , and fr o m n itr o s y l h a e m s , fo r m ed fr o m r e a c tio n of n itr ic

33 , 34o x id e and h a e m s .

- 8 -

1 .3 N IT R IT E A C T IV A T IO N1 .3 .1 P h o to ly s is

A q u eo u s so lu t io n s of n itr ite h ave b een show n to p ro d u ce n itr o g e n 35 35 37o x id e s on p h o to ly s is . ’ * The m e c h a n ism is not fu lly u n d ersto o d ,

but n itr ite s a lt s p ro d u ce N^O^. N itra te sa-lts p ro d u ce both N^O^ andN ° B oth th e se n itr o g e n o x id es a re known to be p o w erfu l n itr o sa t in g“ 16 17a g e n ts u n d er a c id ic , n e u tr a l and a lk a lin e c o n d it io n s . ’ T hus n itr o s o

com p ou n d s sh ou ld be p ro d u ced by p h o to ly s is of n itr ite in the p r e s e n c e o fa m in e s . H o w ev er N -n itr o s a m in es a r e a ls o d e c o m p o se d by p h o to ly s is ,

38p a r t ic u la r ly u n d er a c id ic co n d itio n s . T h e r e fo r e the am ou nt ofN -n itr o s a m in e fo r m e d w il l depend on the co n d itio n s and r e la t iv e quantumy ie ld s of the tw o p h o to c h e m ic a l p r o c e s s e s .

.39C h a llis and L i found the fo r m a tio n of N -n itr o s a m in e s fr o mh e t e r o c y c lic a m in e s u n d er m ild c o n d it io n s . W hen 0. 1M so d iu m n itr ite

o -3in w a te r at 25 C w a s p h o to ly se d in the p r e s e n c e of 5 x 10 M m o rp h o lin e ,a f te r 300 m in u te s th e co n cen tra tio n of N -n itr o so m o r p h o lin e p rod u ced w a s

-33 .4 3 x 10 M. T h e r e fo r e the y ie ld of N -n itr o s a m in e w a s 69%. In the p r e s e n c e of added n itr a te sa lt the N -n itr o sa m in e w a s o b se r v e d to r e a d ily d e c o m p o se on p h o to ly s is . ^

So n itr ite io n ca n be a ctiv a ted by p h o to ly s is to p ro d u ce r e a c t iv e n itr o s a t in g a g e n ts u n d er n o n -a c id ic c o n d it io n s .1 .3 . 2 R a d io ly s is

S im ila r r e a c t io n s to th o se fr o m p h o to ly s is w e r e a ls o o b se r v e d onV -ir r a d ia t io n o f n itr i te so lu tio n s . R a d ica l in te r m e d ia te s su ch a s NO*

and NO* a re know n to be p rod u ced on r a d io ly s is o f a q u eo u s so lu tio n s of 4 0 ,4 1n itr i te . * T h e se r a d ic a ls can then co m b in e to fo r m N^O^.

Q u a n tita tiv e fo r m a tio n of N -n itr o s a m in e s fr o m m o rp h o lin e and42 -3N -m e th y l p ip e r a z in e w a s obtained on r a d io ly s is o f 2 x 10 M a m in e

in 0 . 1 M a q u eo u s so d iu m n itr ite fo r 60 m in s at 1 M rad H r. * The h ig h e s t y ie ld s w e r e o b ta in ed u sin g e x c e s s n itr ite . T he e x c e s s sa lt a tten u a ted the c o n c u r r e n t r a d io ly t ic d e c o m p o s it io n of the p ro d u ct. T h is e f fe c t w a s p r o p o se d to be due to p r e fe r e n t ia l trap p in g by the n itr ite ion o f the h y d ro x y l r a d ic a ls and so lv a ted e le c tr o n s p ro d u ced on V - r a d io ly s i s . T he N -n it r o s a m in e s w e r e thought to be fo r m ed fr o m N O (S ch em e 10).w J

- 9 -

E v id en c e in c lu d ed the r e la t iv e in d if fe r e n c e o f p rod u ct y ie ld s to the s tr u c tu r e and b a s ic ity o f the a m in e , and the in h ib ito ry e f fe c t of added a c id and so d iu m a z id e . Sodium a z id e c o n v e r ts m o s t n itr o sa t in g a g e n ts to n itr o g e n and n itr o u s ox id e (N O).

Cd

y2 NO + H O ---------- ► N O + 2 HOw Cd c* SN O + R NH -----------► R NNO + H O + NO"

Cd 3 Cd Cd Cd Cd

SCHEM E 10

R a d io ly s is of n itr a te so lu tio n s co n ta in in g a m in e s , g iv e s both the N -n itr o s a m in e s and N -n itr o a m in e s , a r is in g fr o m fo r m a tio n of N _ 0 .

Cd TT hus n itr o sa t io n r e a c tio n s can be brought about by r a d io ly s is o f

n itr ite s o lu t io n s , p rod u cin g r e a c t iv e n itr o sa t in g a g e n ts , under n o n -a c id ic c o n d it io n s .1 .3 .3 R ea c tio n w ith A c e t ic A n h yd rid e

In th e ir s tu d ie s o f the s o lv o ly s i s o f a c e t ic a n h y d r id e , L e e s and 43S a v il le o b se r v e d the r e a c tio n to b e m a rk e d ly c a ta ly s e d by n itr ite io n .

oT he r e a c t io n w a s c a r r ie d out in 50% a q u eo u s a ce to n e a t 25 C and the ra te eq u a tio n w as d e ter m in e d (E q uation 2)

R A TE = j k n + k j [AcO"] + k 2 [ n O^] ■ [a c zO] - 2

The r e a c t io n w a s f i r s t o rd er in a c e t ic a n h y d r id e , and sh ow edf i r s t o r d e r te r m s in a c e ta te and n it r i t e . The rate c o e f f ic ie n ts w er ed e te r m in e d a s; k__ = 0 .0 1 1 0 m in * fo r u n c a ta ly se d h y d r o ly s is ,

-1 3 -1k = 0. 0986 m o l dm m in fo r th e a c e ta te c a ta ly se d r e a c t io n and 1 + - 1 3 - 1k = (9 .1 5 - 0 .2 6 ) m o l dm m in fo r the n itr ite c a ta ly s e d r e a c t io n .Cd

D e te r m in a tio n o f the n itr ite c o n c e n tr a tio n at the end of the r e a c t io n c o n fir m e d that i t w as not con su m ed and w as in d eed a c t in g a s a c a ta ly s t .

Tw o ex p la n a tio n s cou ld be p r o p o se d fo r the a c t io n o f n itr ite , i) N itr ite w a s a ctin g a s a g e n e r a l b a s e c a ta ly s t (S ch em e 11). If th is w e r e s o , then the ra te o f the a c e ta te and n itr ite c a ta ly s e d p r o c e s s e s sh ou ld be s im ila r , a s th ey have s im i la r pK ^'s of 4 .7 5 and 3 .4 r e s p e c t iv e ly . In fa c t a c e ta te sh ou ld be the b e tte r b a s e , w h e r e a s

1 0 -

e x p e r im e n ta lly the a c e ta te te r m w as 100 t im e s l e s s than the n itr ite t e r m . T h is w a s th e r e fo r e an u n s a t is fa c to r y exp lan a tio n .

--------- ► C H 3 C O t + C H 3 C 0 2 H + H N ° 2

©

SCH EM E 11i i) N itr ite a c ts a s a n u c le o p h ile , a tta ck in g the an h yd rid e in a b im o le c u la r ra te d e ter m in in g s tep g iv in g an in te r m e d ia te that r a p id ly d e c o m p o s e s to g iv e a c e t ic a cid and n itr i te (S ch em e 12).

N O ? + A c O 2 2

s lo w fa s t——----- ► [ i n t e r m e d i a t e ]

H 2 °SCH EM E 12

N O ? + 2 A c OHLi

43T he seco n d e x p la n a tio n w as fa v o u re d by L e e s and S a v il le . ” T h ey p r o p o se d that the in te r m e d ia te w as an a c y l n itr ite (4) fo r m e d by n u c le o p h ilic a tta c k of the n itr ite io n v ia o x y g en (S c h e m e 13).

+ O - N = OCH

/O

ONO+ CH Cof

(4)

SCH EM E 13E v id en c e fo r th e s tr u c tu r e of the in te r m e d ia te w a s ob ta in ed fr o m

r e a c t io n s c a r r ie d out in the p r e s e n c e o f e x c e s s of (7 -n ap h th y la m in e (5 ). T h is led to the fo r m a tio n o f an a z o -d y e , n a m ely 4 - a m in o - 1, I ' -a z o n a p h - th a le n e (6) (E q uation 3 ).

NH,A c O /NO ®50% aq. A ce to n e

(5 )

- 3

11

The a m ou n ts of the dye p ro d u ced , w h ich w ere d e te r m in e d sp e c tr o p h o to m e tr ic a l ly , c o rresp o n d ed w ith the c a lc u la te d fr a c t io n of the in te r m e d ia te (4 ), th at cou ld be p ro d u ced if i t s h y d r o ly s is w e r e a v o id ed .T he ra te o f fo r m a tio n o f the dye w a s a ls o c o n s is te n t w ith fo r m a tio n o f the in te r m e d ia te . W ith a la r g e e x c e s s o f d -n a p h th y la m in e a lm o s t q u a n tita tive fo r m a tio n of (6) w a s o b ta in ed .

It w a s p ro p o se d th at the a c e ty l n itr ite w as in d eed fo r m e d , and a c ted a s a n itr o sa t in g a g en t to d ia z o t is e the am in e (S ch em e 14). So r e a c t io n o f n itr ite io n w ith a c e t ic a n h yd rid e in 50% a q u eo u s a c e to n e , a c t iv a te d the n itr ite ion a s a n itr o sa t in g a gen t, under m ild n o n -a c id ic c o n d it io n s .

O - NO Oq(4)

SCH EM E 14

S im ila r r e a c t io n w a s a ls o o b se r v e d w ith e th y l c h lo r o fo r m a te , v a r io u s 4 - su b stitu ted b e n z o y lc h lo r id e s , and s u c c in ic and b u ty r ic a n h y d r id e s . ^1 .3 .4 R ea c tio n w ith Im in iu m C a tio n s

44K e e fe r and R o lle r o b se r v e d c a t a ly s is of N -n itr o s a m in efo r m a t io n by fo r m a ld e h y d e at pH 6 -1 1 . A qu eous n itr ite i s know n not tor e a c t w ith a m in e s a t pH ^ 7 . 5 . A ran g e o f seco n d a ry a m in e s w er ee a s i ly n itr o sa te d in a lk a lin e fo rm a ld eh y d e so lu tio n . Y ie ld s ofN -n itr o s a m in e w e r e lo w , b ein g l e s s than 1% at p H } 6 . C h lo r a l w asa ls o a c a ta ly s t a lth ou g h a ce to n e and 2, 2 -d im e th y lp r o p io n a ld e h y d e w ere

45u n r e a c t iv e . O ther g ro u p s have o b se r v e d the p h en om en o n . T annenbaum 46and c o -w o r k e r s found p y r id o x a l and b en za ld eh y d es to a ls o a c t a s

47c a t a ly s t s , a s d id m a lo n d ia ld eh y d e .A m e c h a n ism w a s p ro p o sed to a cco u n t fo r th e s e o b s e r v a t io n s

(S ch em e 15). T h is in v o lv e d fo r m a tio n of the im in iu m c a tio n (7) fr o m r e a c t io n of the a m in e w ith the a ld eh y d e . T h is s p e c ie s i s h ig h ly r e a c t iv e tow ard n u c le o p h ile s and cou ld be a tta ck ed by n itr ite io n a s sh ow n , to g iv e the adduct (8 ). R e a r r a n g e m e n t o f the n itr o so g ro u p , fr o m oxy g en

1 2 -

to n itr o g e n , and c o l la p s e o f the in te r m e d ia te , p ro d u c es the N -n itr o sa m in e and r e g e n e r a te s the a ld eh y d e .

HOR R J H + O = CHR ---------1 u

©R 1R 2N

PiNIIO

CHR -

tR R N -N = 0 + R C H = -0

L M

( 8)

SCH EM E 15 4 4 , 48K e e fe r and R o lle r ’ found th at re a c tio n of the im in iu m ca tio n

fr o m d im eth y la m in e and fo r m a ld e h y d e , w ith s i lv e r n itr ite in anh yd rou s a c e to n it r i le , p rod u ced a q u a n tita tive y ie ld of the N -n itr o s a m in e .

R ec e n tly d e ta ile d k in e t ic s tu d ie s of the s y s te m h av e b een c a r r ie d 4 9 ,5 0out. ’ The v a r io u s e q u ilib r ia b e tw e e n the a m in e and fo rm a ld eh y d e ,

in i t s h yd rated fo r m (9) w e r e taken in to accou n t (S ch em e 16). The in it ia l ra te of n itr o s a t io n o f m o rp h o lin e ( r Q) obeyed eq u a tio n 3, w h ere the im in iu m ca tio n c o n c en tr a tio n w a s p ro p o rtio n a l to the co n cen tra tio n o f p ro to n a ted c a r b in o la m in e (10 ).

r = kK [NO " ] [R N+HCH0 OH] o 5 L 2 J o L 2 2 J(10)

- 3

13 -

K, R2NH K3

r2nh + H2C(OH)2 ------R2N-CH2OH

(9) H20 H20

r 2n c i-i2n r2

KQ1 H" KQ2 H Ka3 H+

K-

R2 NH2 + H2C(OH),+

r 2nh

r2nhch2oh R2NCH2NHR2

H70 (10) h 2o

K, h2o

r 2n — c h2

SCHEME 16

14 -

The eq u ilib r iu m c o n sta n ts fo r fo r m a tio n of the n e u tr a l and c a t io n ic c a r b in o la m in e , K and K , w ere o b se r v e d to be m o re d ep en d en t on the

JL C*s t e r ic a c c e s s ib i l i t y o f the n itro g en a to m than on the p o la r c h a r a c te r of the a m in e . T h is w a s in a g r e e m e n t w ith the o rd er o f y ie ld s of

44N -n itr o sa m in e fr o m v a r io u s a m in e s , found by K e e fe r and R o lle r .The y ie ld s v a r ied in the o r d e r , p y r o llid in e p ip er id in e d im e th y la m in e

> d ie th y la m in e ^ d i - np r o p y la m in e /»)> d iiso p r o p y la m in e . T h ey w er e a ls o d ep end en t on s t e r i c e f fe c ts due to the a ld eh yd e a lk y l group ex p la in in g w hy 2, 2 -d im e th y lp r o p io n -a ld e h y d e w as not a c a ta ly s t . T he ra te l im it in g step cou ld be e ith e r r e a c t io n of the n itr ite io n w ith the im in iu m ca tio n , or d e c o m p o s it io n o f the adduct fo rm ed fr o m th em .

1 5 -

1 .4 THE REACTIO NS OF H ETER O C U M U LEN ES1 .4 .1 Iso cy a n a tes

T he o rg a n ic is o c y a n a te s (11) a re fo r m a lly the a n h y d r id es o f the c a r b a m ic a c id s (12 ). T h ey h ave a h e te r o c u m u le n e s tr u c tu r e , co n ta in in g the u n sa tu ra te d , l in e a r -N = C = O grou p .

O

R - N = C = O R - NHOH

(11) (12)

T h ey a r e a v e r y r e a c t iv e c la s s of com p ou n d s b ein g v e r y h ig h lys u s c e p t ib le to n u c le o p h ilic a tta ck . The a tta c k ta k e s p la c e a t thee le c tr o n d e f ic ie n t a c y l ca rb o n a tom of the h e te r o c u m u le n e s tr u c tu r e .

T he c h e m is tr y of th e iso c y a n a te s h a s b ee n e x t e n s iv e ly stu d ied due5to th e ir in d u s tr ia l im p o r ta n c e . In 1974 w o r ld p ro d u ctio n rea ch ed 10

51 .ton s p e r ann um . Of t h is , 90% w as a cco u n ted fo r by tw o com p ou nd s; +olo?.nC.toiy lo n c d i- is o c y a n a te and d ip h en y lm eth an e d i- i s o c y a n a t e , both v e r y im p o rta n t a s m o n o m e r s in the p o ly m er in d u str y .

5 2 ,5 3 ,5 4 , 55A n u m b er o f e x c e l le n t r e v ie w s a lr e a d y e x is t , so on lyr e le v a n t and r e c e n t d e v e lo p m e n ts w ill be d is c u s s e d h e r e .

I so c y a n a te s r e a c t w ith m o st n u c le o p h ile s . R e a c tio n w ith a lc o h o ls g iv e s u r e th a n e s , w ith a m in e s g iv e s u r e a s , and w ith th io ls g iv e s th io u r e th a n e s . The r e a c t io n s of is o c y a n a te s w ith n u c le o p h ile s a re s u m m a r is e d in S ch em e 17. Iso c y a n a te s a r e r e a d ily h y d r o ly se d by w a ter g iv in g , a f te r lo s s of CO , an am in e w h ich r e a c ts fu r th e r to g iv e the u r e a .

16 -

The c a t a ly s is o f m an y of th e se r e a c t io n s by a v a r ie ty of L ew is

17

A AR - N = C = O R — NH- //O R = A LK Y L- R - N- / /O

OH CH°'::̂ S n o h

Me

CH3~ A o

3 O

( 1 3 )

R N C O /C H CO HJ L*

o oR = A R Y L

- CO,PA (14)R — NH

O O CH3CH ^ ^ O ^ ^ C H 3 + R N H ^ ^ O ^ ^NH R

(15)

* - C° 2R N H ^ ^ N H R

( 16)

SCHEM E 18R e a c tio n of a r y l is o c y a n a te s w ith 4 -n itr o p h e n o l in the p r e s e n c e o f

p o ta s s iu m carb o n a te g iv e s the u reth a n e (17) w hich on h ea tin g e x tr u d e s5 6 ,5 7 ,5 8CO g iv in g the a m in e (18) (S ch em e 19).

N ° 4 A OHK 2C ° 3 /P h N ° 2190

*N = C = O

O

N 0 2\ / x

SCH EM E 19F e w r e a c t io n s o f is o c y a n a te s a r e c a r r ie d out in a q u eou s so lu tio n .

B oth a lip h a tic and a r o m a tic is o c y a n a te s h o w ev er r e a c t w ith a q u eo u s b isu lp h ite so lu tio n s to g iv e s ta b le , w a te r so lu b le ad d u cts in h igh y ie ld s (S ch em e 20). ^ The a d d u cts (19) w il l th en r e a c t w ith b e n z y la m in e tog iv e the u rea and r e g e n e r a te the b isu lp h ite . Thus the b isu lp h ite io n i s s u f f ic ie n t ly n u c le o p h ilic to c o m p ete w ith h y d r o ly s is d e sp ite the la r g e

18 -

e x c e s s of w a te r .

R -N = C = O + HSOSO.

PhCH NH |j-------- R N H ^ N H C H Ph

+

H SO l

SCH EM E 20N u c le o p h ilic a c y la t io n of is o c y a n a te s by rea c tio n w ith a c y l

lith iu m r e a g e n ts h as b ee n d e m o n s tr a te d ^ (S ch em e 21), g iv in g d ir e c ta tta c k of the o rg a n o lith iu m rea g en t a s a s id e rea c tio n . The r e a c t io n of

62is o c y a n a te s w ith o th er o r g a n o m e ta ll ic s p e c ie s i s w e ll know n.O

RNH

R 'iL i/C O + RNCOLow

T Li®

H3 °R 'C — C — NHR

II II o oSCH EM E 21

A n in te r e s t in g r e a c t io n o f is o c y a n a te s i s that w ith p e r o x y com p ou n d sA t low te m p er a tu r e r e a c t io n of e q u im o la r q u a n titie s of is o c y a n a te and

6 3 64p e r o x id e gave p e r o x y c a r b a m a te s * (2 0 ). T h ese a re u n sta b le and65 66d e c o m p o se w ith lo s s of CO^ to g iv e a zo a n d /o r h yd ra zo com p ou n d s

(S ch em e 22). A p aten t w a s is s u e d fo r c o m m e r c ia l p ro d u ctio n of a z o67com p ou n d s by r e a c t io n o f e th e r e a l h y d ro g en p ero x id e and is o c y a n a te s

A n a n a ly t ic a l p r o c e d u r e w a s d ev e lo p e d u s in g the c o lo r im e tr ic r e a c t io n of68p h en y l is o c y a n a te s and p e r o x id e s u n d er b a s ic co n d itio n s . T he c o lo u r e d

p ro d u c t fo r m ed w a s not an a zo com p ou nd , but thought to be n itr o so b e n z e n e (2 1 ), fo r m ed fr o m o x id a tio n of the r a d ic a l (2 2 ).

19 -

O

R - N = C = O + R'OOH

RNHNHR + R - N = N - R(22)

SCH EM E 22

)— N = 0

N----- '(21 )

V e r y l it t le w ork h a s b een done on the n itr o sa tio n o f i s o c y a n a te s .R e a c tio n of phenyl iso c y a n a te w ith N O in c h lo ro fo r m w a s found to

2 4 69g iv e h igh y ie ld s of b en zen e d ia zo n iu m n itr a te (13) (S ch em e 2 3 ).CHC1

PhN CO + N 00„ 2 4 PhN + NO" + CO(13)

SC H EM E 23 70Olah and c o -w o r k e r s exa m in ed the r e a c tio n o f is o c y a n a te s w ith

n itr o so n iu m s a lt s . T h is gav e the ca rb o n iu m ion (S ch em e 24) w h ich w a s id e n tif ie d by n. m . r.

MeNOR - N = C = O + NO x ” ------------ ► R+ x “ + N + CO

R = (C 6H5 )3C - . (CH 3 )3 C - , C 6Hs O -SCH EM E 24

C a rry in g out the r e a c t io n in the p r e s e n c e of an a r o m a tic com pound r e s u lte d in a lk y la tio n of the a r o m a tic r in g . The r e a c tio n m u s t tak e p la c e v ia a tta ck of the n itr o so n iu m ion on the iso c y a n a te , then r e a r r a n g e m e n t and fr a g m e n ta tio n (S ch em e 25) . A s im ila r m e c h a n ism m u st ta k e p la c ein the r e a c t io n w ith N _ 0 .2 4

R - N = C = O + NOX'

N= OIR - ^ = C = O X R + N + CO

X" Z LSCH EM E 25

The o th er im p o rta n t c la s s of iso c y a n a te r e a c t io n s a re the 1 ,2 -

2 0

d e ta il h e r e . H o w ever one r e c e n t ex a m p le in v o lv e s the d e n itr o s a t io n of71N -n itr o s a m in e s by N -c h lo r o su lp h o n y l iso c y a n a te (S ch em e 2 5 ). T h is

w a s thought to in v o lv e c y c lo a d d itio n , then fr a g m e n ta tio n of the 4 -m e m b e r e d ring to g iv e CO and the N -c h lo r o su lp h o n y l t r ia z e n e (23) w h ich h y d r o ly s e s to the a m in e under the r e a c tio n c o n d it io n s . H igh y ie ld s o f a m in e w er e ob ta in ed .

c y c lo a d d itio n s a c r o s s the C = N bond. T h ese w ill not be d is c u s s e d in

R i \ N - N = O E t2 °R

R.

C1SO - N = C = Ow

l \ H 2 °N - N = NH ------—

RH

R

R, (23)

iNv n h

VSCH EM E 25

1 .4 .2 Iso th io c y a n a te sT he iso th io c y a n a te s (24) a re the th io a n a lo g u e s of the i s o c y a n a te s ,

and the a n h y d r id es of the th io c a r b a m ic a c id s (25).S

R - N = C = S

(24)

R - NH-

(25)

//OH

T h ey ex h ib it s im ila r p r o p e r t ie s to the is o c y a n a te s but a r e l e s s72r e a c t iv e . I so th io c y a n a te s a re a tta ck ed by a w ide ran g e o f n u c le o p h ile s

in c lu d in g a lc o h o ls , a m in e s and th io ls . R ea ctio n w ith c a r b o x y lic a c id s g iv e s a m id e s (S ch em e 27) but h igh te m p e r a tu r e s ( /> 130°C ) a r e r e q u ir e d .

- 2 1

R - N = C = S + R'CO Hc*

RNH-

R'

//

O

O

- R N H ^ + COS R'

O

SCHEM E 27Iso th io c y a n a te s a re s ta b le to w a te r , o ften being p u r ified by s te a m

d is t i l la t io n . No ten d en cy fo r d im e r iz a t io n and tr im e r iz a t io n h a s b een o b s e r v e d .

A d d u cts a re fo rm ed fr o m r e a c t io n o f iso th io c y a n a te s w ith a q u eo u s 73b isu lp h ite so lu tio n . O rg a n o lith iu m r e a g e n ts u nd ergo n u c le o p h ilic

74a d d itio n to is o th io c y a n a te s . U s in g a c y llith iu m r e a g e n ts S e y fe r th and Hui^* o b se r v e d in te r e s t in g b eh a v io u r of the a n ion s fo rm ed (S ch em e 28).

H 3° +

-110B u L i/C O + RNCS ■fcBuC

IIO

̂ © LiNR

.€>

( 26)

c h 3 i

BuC - C - NHRII II o s(27)

'BuC - C - SCHII H 3O NR(28)

SCH EM E 28The in te r m e d ia te (26) cou ld b e tra p p ed by a cid to g iv e the

th io c a r b o n y l com pound (27) v ia N -p ro to n a tio n . Trapping w ith m e th y l io d id e , h o w ev e r p ro d u ces the im in e (28) a s a r e s u lt of S -a lk y la t io n .T h is i s r a t io n a lis e d by the HSAB th e o r y , a s the h a rd er e le c tr o p h ile (H +) r e a c ts on the h a rd er a to m (N) o f the a m b id en t anion (26) and the s o f te r e le c tr o p h ile (M el) a t the s o f te r su lp h u r a to m .

R e c e n t s tu d ie s o ften c o n c e r n the m o r e r e a c t iv e c la s s e s o f is o th io c y a n a te s su ch a s the a c y l (2 9 ), su lp h o n y l (30), and p h o sp h o r y l (31) d e r iv a t iv e s , w h ich a re c o m m o n ly u se d in s y n t h e s is .

O j— OR - C - N = C = S R - SO - N = C = S ( F (0 )N = C = S

L '— O

(29) (30) (31)

- 2 2 -

O nly one study on the n itr o sa t io n of iso th io c y a n a te s a p p e a r s to have70b een d o n e . O lah and c o -w o r k e r s found that a lk y l and a c y l is o th io c y a n a te s

r e a c te d w ith NO s a lt s in n itro m eth a n e to g iv e d ea m in a tio n , in a s im ila r fa sh io n to the is o th io c y a n a te s , (S ch em e 29).

R - N = C = S + NO+ SbFM eNO.

R+ SbF ” + + COSo 2SCH EM E 29

1 .4 .3 C a rb o d iim id esThe c a r b o d iim id e s (32) a re the a n h yd r id es of the u r e a s (3 3 ). T hey

h ave a h e ter o cu m u le n e s tr u c tu r e w ith a c e n tr a l e le c tr o n d e f ic ie n t carb on a to m and a r e r e a d ily a tta ck ed by n u c le o p h ile s .

OiiR 1 - N = C = N - R 2 R jNH - C - NHR

(32) (33)C a r b o d iim id e s a re l e s s r e a c t iv e than is o c y a n a te s but m o r e r e a c t iv e

than is o th io c y a n a te s .75 76The c h e m is tr y of c a r b o d iim id e s has b een w id e ly r e v ie w e d . *

It i s w e l l known that c a r b o d iim id e s r e a c t w ith a w id e ran ge of n u c le o p h ile s , su ch a s a m in e s , th io ls , h y d ro x y la m in e e tc . T hey r e a d ily h y d r o ly se to the p a ren t u r e a . A lc o h o ls a r e u su a lly in e r t tow ard c a r b o d iim id e s u n le s s a su ita b le c a ta ly s t , su ch a s Cu C l or CuCl_ , i s p r e s e n t . E v en

C* Cd c*

r e a c t io n w ith a lk o x id e s r e q u ir e s h igh te m p e r a tu r e . C a r b o d iim id e s d im e r iz e a s do is o c y a n a te s , and m a y p o ly m e r iz e on h ea tin g .

One of the m o st im p o rta n t r e a c t io n s of c a r b o d iim id e s is w ith c a r b o x y lic a c id s . It g iv e s h ig h ly r e a c t iv e m ix ed a n h yd r id es w h ich a re u sed a s r e a g e n ts in bond m ak in g p r o c e s s e s , su ch a s the s y n th e s is of p e p tid e s and p h osp h ate e s t e r s . D ic y c lo h e x y lc a r b o d iim id e (DCC) is u su a lly u s e d . F o r e x a m p le S ch em e 30 sh ow s the u se o f DCC in p ep tid e fo r m a tio n , w h ere the m ix e d an h yd rid e (34) i s fo rm ed and r e a c te d w ith a p r o te c te d am in o a c id (35) to g iv e the d ip ep tid e (36).

- 2 3 -

R NHCHCO H + C y -N = C = N -C y1 L*

R 2

0 -C 0 C H N H R 1 C y-N — -----NH — Cy

+

(C y = c y c lo h e x y l)

OiiC y - H N - C - N H - Cy

(38)SCH EM E 30

The tw o p ro b le m s w ith th is r e a c tio n a r e com p etin g r e a r r a n g e m e n tof the a n h yd rid e by an O -----► N a c y l sh ift g iv in g (3 7 ), and the d iff ic u ltyo f rem o v in g the d ic y c lo h e x y l u rea (38) s id e p ro d u ct. T h ese d if f ic u lt ie sa r e o v e r c o m e by em p lo y in g p o ly m e r su p p orted u n s y m m e tr ic a lly

80d isu b stitu ted c a r b o d iim id e s ! the p o ly m e r su p p ort e n s u r e s fr e e d o m fr o m u r e a and the d if fe r e n t ia l e le c tr o n d e n s ity r e d u c e s the e a s e o f the a c y l sh if t .

C a r b o d iim id e s a re a ls o u sed to p ro m o te y lid e fo r m a tio n b etw eend im e th y l su lp h o x id e (DMSO) and h yd roxy com p ou n d s in the P f i t z n e r -

81 , ,M offat o x id a tio n of a lc o h o ls (S ch em e 31). N u c le o p h ilic a tta ck of DMSO on the ca r b o d iim id e g iv e s the r e a c t iv e anh yd rid e (3 9 ).

DCC + DMSO H 3P ° 4Me,CHOH o"2''"n v n ||C y - N =~|— N H - C y ► C y -N H -C -N H -C y

•Me

MeY=lO + DMSO

(39)

H 2°

0 — sMe

Me CHO — SCd

Me

Me

MeS C H E M E 3 1

- 24 -

R ea c tio n of c a r b o d iim id e s and h yd ro g en p er o x id e h as b een u sed to82p ro d u ce o x id is in g a g e n ts . R eb ek and c o -w o r k e r s found r e a c t io n of

v a r io u s d eh yd ratin g a g en ts su ch a s a c tiv a te d u r e a s , c y a n a te s and ortho e s t e r s r e a c te d w ith h y d ro g en p ero x id e to g iv e e p o x id is in g a g e n ts .DCC fa ile d in th is r e s p e c t u n le s s a c e t ic o r tr if lu o r o a c e t ic a c id w a s add ed , and th is w as thought to p rod u ce a p e r a c id a s the e p o x id is in g a g en t. U sin g a m o re r e a c t iv e c a rb o d iim id e h o w ev e r , w ith a b en zo y l su b stitu en t, ep ox id atio n of a lk e n e s w as obta ined by r e a c tio n w ith h yd ro g en p er o x id e and ca rb o d iim id e in T H F. The ep o x id e w a s a ls o d e c o m p o se d u n d er the r e a c tio n c o n d itio n s , fo r ex a m p le r e a c t io n w ith c y c lo h e x e n e g av e 41% ep ox id e but on ly 25% r e c o v e r e d a lk e n e . R ea c tio n of h y d ro g en p er o x id e w as thought to fo r m an in te r m e d ia te (40) (S ch em e 3 2).

R = PhC - R 2 = l Bu -

SCH EM E 3283O ther w o r k e r s h av e o b se r v e d ep o x id a tio n o f p y ren e and

p h en an th ren e by a m ix tu r e of d iiso p r o p y lc a r b o d iim id e , a c e t ic a c id and h yd ro g en p e r o x id e , p r e su m a b ly by fo r m a tio n of a p e r a c id (S ch em e 33)

S C H E M E 3 3

- 25 -

The u n r e a c tiv e c a r b o d iim id e s m ay e ith e r not r e a c t w ith h y d ro g en p e r o x id e , or i f r e a c tio n o c c u r s then the u n sta b le a n io n fo r m ed m a y trap out the p er o x id e in te r n a lly g iv in g an N -h y d ro x y com p ou nd (41) and co n seq u en tly no ep o x id a tio n of a lk e n e s (S ch em e 3 4).

R - N C = N - RL >

/

© !R — N — C - N — RI IIO OH

H+ 1-----► RN — C — NHROH O

(41)

SCH EM E 341 .4 .4 N -S u lp h in y l A m in e s

84 85The N -su lp h in y l a m in e s (42) h ave not b een m u ch stu d ied .T h ey a re e a s i ly p re p a r e d by the a c tio n of th io n y l c h lo r id e on a m in e s (S ch em e 35), the a lip h a tic d e r iv a t iv e s b ein g le a s t s ta b le .

RNH2 + SO C l2 ------------ ► R - N = S = O + 2HC1(42)

SC H EM E 35T h ey a re a ttack ed by n u c le o p h ile s but a r e l e s s r e a c t iv e than the

oth er h e te r o c u m u le n e s . Indeed th ey do not p o s s e s s the sa m e type o f s tr u c tu r e . The -N SO grou p i s n o n - lin e a r , and g iv e s c is and tr a n s i s o m e r s . (S ch em e 36)

-N O

Ph SCH EM E 36

-N

OIIs+

Ph

T hey do not h ave the ty p ic a l i . r . a b so r b a n c e o f h e te r o c u m u le n es tr u c tu r e s at around 2200 cm but have an i . r . s p e c tr a v e r y s im ila rto that of S 0 2> su g g e s t in g a s im ila r n o n - lin e a r s tru c tu r e .

N -su lp h in y l a m in e s r e a c t w ith w a ter to g iv e the p a ren t a m in e andSO . A lc o h o ly s is a ls o g iv e s the a m in e , a s the in it ia l adduct i s u n sta b le

c*

and d e c o m p o s e s . A m in e s and th io ls r e a c t a s do G rig n a rd r e a g e n ts and o rg a n o lith iu m r e a g e n ts .

- 26 -

70O lah found that N -su lp h in y l a m in e s r e a c te d w ith n itr o so n iu m s a lt s in n itr o m e th a n e to g iv e carb on iu m io n s (S ch em e 37).

R - N = S = O + NO+ SbF ” ------- ► R+S bF ~ + N_ + SO„6 6 2 2r = (c h 3 )3 c - , (c 6h 5 )3 c - , c 6h 5 c o

SCHEM E 37

A r o m a t ic d e r iv a t iv e s re a c te d w ith n itr o so n iu m s a lt s in e th y len e88d ic h lo r id e to g iv e d ia zo n iu m s a lt s (S ch em e 38)

R - N = S = O + NO+ X" -------------► RN* X" + SOM Ld

X = CIO , SbC l N02

R = N 0 2 - < Q > - »

SCH EM E 38

- 27 -

1 .5 C O NCLUSIO NT h e se e x a m p le s show that n itr ite io n can be a c tiv a te d to p ro d u ce

n itr o s a t io n r e a c t io n s , by both p h y s ic a l and c h e m ic a l m e a n s . N itr ite a c t iv a t io n o f f e r s m eth od s of p ro d u c in g n itr o sa t io n r e a c t io n s under m ild , n o n -a c id ic c o n d it io n s .

R e a c t io n s o f th is type m a y be im p o rta n t fo r tw o r e a s o n s . F ir s t ly , th ey g iv e p o s s ib le rou tes fo r the fo r m a tio n o f c a r c in o g e n ic m a te r ia ls in the e n v ir o n m e n t. P h o to ly s is o f n itr ite io n to p ro d u ce n itr o so com p ou n d s m a y be im p o r ta n t w ith r e s p e c t to the s to r a g e of fo o d s con ta in in g n itr i te .A n ex a m p le i s th e s to r a g e of b acon in se e - th r o u g h p a ck s in f lu o r e s c e n t l i t c a b in e ts . N itr o sa t io n c a ta ly se d by fo rm a ld eh y d e a ls o has e n v iro n m e n ta l im p o r ta n c e , a s fo rm a ld eh y d e i s u sed a s a g e r m ic id e and fu n g ic id e fo r p la n ts and v e g e ta b le s and in co m b in a tio n w ith n itr ite a s a f i s h p r e s e r v a t iv e .

S ec o n d ly th e s e m ild m eth od s o f n itr o s a t io n m a y be u se fu l in s y n t h e s is . D ea m in a tio n u su a lly o c c u r s u n d er a c id ic co n d itio n s , w h ich m a y be u n a cc e p ta b le fo r m u ltifu n c tio n a l co m p ou n d s.

The c h e m ic a l m eth od s o f a c t iv a t io n both in v o lv ed re a c tio n o f n itr ite io n w ith a n h y d r id es . The h ig h r e a c t iv ity of the h e ter o cu m u le n e a n h y d r id es to n u c le o p h ilic a d d itio n h a s b ee n d is c u s s e d . T h ese a re th e r e fo r e id e a l s u b s tr a te s fo r r e a c t io n w ith n itr ite io n .

The w o rk d e s c r ib e d in th is t h e s is i s d ir e c te d to w a rd s ex a m in in g the r e a c t io n o f n itr ite ion w ith th e se o r g a n ic a n h y d r id es and to in v e s t ig a te the p o s s ib i l i t y o f a c t iv a tio n of the n itr ite ion to g iv e n itr o sa tio n r e a c t io n s u n d er m ild c o n d it io n s .

CH APTER 2

R EA C T IO N OF NITRITE ION WITH ARO M ATIC ISOCYANATES

- 29 -

2 . 1 INTRODUCTION

The is o c y a n a te s a r e the m o s t r e a c t iv e c la s s of a n h yd rid es e x a m in e d and the p a r t ic u la r ly h igh r e a c t iv ity o f the a ro m a tic com pounds r e la te s to e le c tr o n w ith d ra w a l by the a ro m a tic g ro u p , in c r e a s in g the e le c tr o n d e f ic ie n c y at the iso c y a n a te grou p .

R ea c tio n of iso c y a n a te s w ith a c e t ic a c id is w e ll known ( s e e S e c t io n 1 .4 . 1). The pKa of a c e t ic a c id i s 4 .7 5 , and s im ila r to th at of n itr o u s a c id , w h ich i s 3 .4 . Thus so m e r e a c tio n shou ld be e x p e c ted b etw e e n the o rg a n ic iso c y a n a te s and n itr ite ion , e x p e c ia lly w ith the m o r e r e a c t iv e a r o m a tic com p ou n d s. T h e s e r e a c tio n s a re rep o rted in th is c h a p ter .2 . 2 H ETERO GENO US REACTIO N

The f i r s t ev id en c e fo r a tta ck by n itr ite ion on the iso c y a n a te c a m e fr o m a s im p le h e tero g en o u s r e a c t io n . S tir r in g a m ix tu re of so lid so d iu m n itr ite and liq u id p h en yl iso c y a n a te p ro d u ced a so lid m a s s a fte r f iv e h o u rs at ro o m te m p e r a tu r e . The p rod u ct c o n ta in e d unchanged so d iu m n itr ite and a g r e a te r than 91% y ie ld of the t r im e r of phenyl iso c y a n a te (S ch em e 3 9 ). S tir r in g p h en yl iso c y a n a te in the a b s e n c e o f sod iu m n itr ite gave o n ly s m a ll am ou n ts of tr im e r w ith m o st o f the iso c y a n a te u n rea c ted .

Sod iu m n itr ite w as a ctin g a s a c a ta ly s t fo r the tr im e r iz a t io n . D is s o lu t io n of a s m a ll am ount of n itr i te in the iso cy a n a te r e s u lt s in n u c le o p h ilic a tta ck of the n itr ite on the iso c y a n a te (S ch em e 39). A n a n io n ic in te r m e d ia te (43) is p ro d u ced and in the p r e se n c e of su ch a la r g e e x c e s s of iso c y a n a te it a tta ck s a s e c o n d m o le c u le . The d im e r ic a n io n (44) p rod u ced can e ith e r c y c l is e v ia a fo u r -m e m b e r e d tr a n s it io n s ta te to g iv e the d im e r (45 ), o b se r v e d a s an im p u r ity , or a tta ck a th ird is o c y a n a te m o le c u le to g iv e (4 6 ). F in a lly (46) c y c l i s e s v ia a m o re fa v o u red6 -m e m b e r e d tr a n s it io n s ta te to g iv e the tr im e r (47) and r e g e n e r a te n itr ite io n .

A ran ge o f o th er n u c le o p h ile s a r e known to c a ta ly se th is r e a c t io n ,89 , 90 91in c lu d in g tr ie th y la m m e , so d iu m m e th o x id e , p o ta ss iu m a c e ta te

91and so d iu m c a rb o n a te .E v id en ce th e r e fo r e im p lied th at n itr ite did in d eed a tta ck p h en y l

i s o c y a n a te . A t th is s ta g e it w as not know n w heth er n itr ite w as a c t in g a s

- 3 0 -

©- n o 2

©- n o 2 Q

P h ------N N — Ph

0

(47 ) (45)

S C H E M E 39

31

an o x y g e n -c e n tr e d n u c leo p h ile a s d ep ic ted in sc h e m e 39, or a s a n itr o g e n - ce n tr e d n u c leo p h ile .

M ore in te r e s t in g r e a c t io n s req u ired the m in im iz a t io n of the tr im e r iz a t io n r e a c tio n , b e c a u se h av in g b een u sed a s an in it ia l p ro b e fo r r e a c t io n it w as now u n d e s ir a b le .2. 3 REACTIO N UND ER AQUEOUS CONDITIONS

Iso c y a n a te s a re v e r y s u s c e p t ib le to h y d r o ly s is and it i s g e n e r a lly in a d v isa b le to u se th em under a q u eou s co n d itio n s .

H ow ever one r e a c t io n w a s a ttem p ted b etw een p h en y l is o c y a n a te and aq u eo u s sod iu m n itr ite . T he r e a c t io n w a s fa ir ly h e te r o g e n o u s due to the low so lu b ility o f p h en yl iso c y a n a te in w a te r . A s e x p e c te d h y d r o ly s is to g iv e the d ip h en y lu rea (48) w as the m a jo r r e a c tio n (S ch em e 4 0 ) . H o w ev er tw o y e llo w com p ou nd s w e r e o b se r v e d by t ic e x a m in a tio n , but in s m a ll a m ou n ts and th ey w er e not fu r th er id e n tif ie d .

/ I AP h — N = C = 0

H20:

0

PhNH ^ -N H P h

(48)

. P h — Nl-I

0

- C O 2

PhN = C = 0

Ph — NH2

SCH EM E 40T h ese tw o r e a c t io n s p ro d u ced th r ee im p o rta n t o b s e r v a t io n s .

1. N itr ite d id in d eed a tta ck p h en y l iso c y a n a te .2. A qu eous co n d itio n s had to be a vo id ed due to h y d r o ly s is of the

iso c y a n a te .3 . L arge e x c e s s of iso c y a n a te p ro d u ced m a in ly t r im e r .2 .4 REACTIO N OF P H E N Y L ISO CYANATE IN ORGANIC SO L V E N T S2 .4 . 1 T o lu en e

In o rd er to c a r r y out r e a c t io n s in o rg a n ic s o lv e n ts it w a s d e s ir a b le92to s o lu b il iz e th e s a lt . A p o te n tia l a n sw e r w as the u se of crow n e t h e r s .

- 3 2 -

R ea c tio n w a s c a r r ie d out in to lu en e u sin g l8 - c r o w n -6 and so d iu m n itr ite .W ith p h en y l iso c y a n a te a c o m p le x r e a c t io n a p p a ren tly en su ed g iv in g a h ig h ly c o lo u r e d so lu tio n . P r o d u c ts in c lu d ed the iso c y a n a te d im e r and t r im e r , so m e h y d r o ly s is and so m e v e r y p o la r m a te r ia l . A ls o obtained w a s 1, 3 -d ip h e n y ltr ia z e n e (49) in 6% y ie ld .

P h -N = N -N H -P h (49)

A ttem p ts w er e m ade to o p tim iz e the y ie ld o f the tr ia z e n e . B y s lo woa d d itio n of the p h en y l iso c y a n a te to the n itr ite so lu tio n a t -3 C , a y ie ld

o f 22% w as a c h ie v e d . No fu r th er im p r o v e m e n t cou ld be m a d e .It a p p ea red that p oor s o lu b il ity of the n itr ite w a s th e p ro b le m .

T he crow n e th e r w a s a ctin g m a in ly a s a p h a se t r a n s fe r c a ta ly s t , taking th e n itr ite in to so lu tio n a s the r e a c t io n p r o c e e d e d . E v en e x c e s s 1 8 -c r o w n -6 w ould not d is s o lv e a l l the n itr ite at o n c e . T h is led to the p r e s e n c e of n itr ite w ith e x c e s s iso c y a n a te and e x te n s iv e tr im e r iz a t io n .So the b est y ie ld w a s obta ined by s lo w a d d ition o f is o c y a n a te to the n itr ite so lu tio n .2 . 4 . 2 A c e to n itr i le

A n o th er p o te n tia l m eth od of so lu b il iz in g the n itr ite ion w a s to93p r e p a r e the te tr a e th y la m m o n iu m s a lt . M ix in g e q u im o la r q u a n titie s

o f s i lv e r n itr ite and te tr a e th y la m m o n iu m b ro m id e in a c e to n it r i le , p r e c ip ita te d s i lv e r b ro m id e and th en r e m o v a l o f the so lv e n t at red u ced p r e s s u r e gave the te tr a e th y la m m o n iu m n itr ite (T E A N ) (S ch em e 4 1 ). R e c r y s ta l l iz a t io n gave fu r th er p u r if ic a tio n .

M eCNAgNO_ + E t . N B r — ■ ----- ► E t . NNO_ + A g B r2 4 4 2(TEA N )

SCH EM E 41

T E A N w a s so lu b le in a ra n g e o f p o la r o r g a n ic s o lv e n t s . S ilv e r n itr ite i t s e l f w a s o n ly s l ig h t ly so lu b le in a c e to n it r i le .

R e a c tio n s w e r e f i r s t c a r r ie d out in a c e to n it r i le , and u n d er th e se c o n d itio n s p h en y l iso c y a n a te r e a c te d w ith n itr ite ion to g iv e 1 ,3 - d ip h e n y ltr ia z e n e in 15-16% y ie ld .

- 3 3 -

2 .5 R EA C TIO N OF 4-N IT R O PH E N Y L JSO C Y A N A T E IN A CETO N ITR ILEA m o re r e a c t iv e su b str a te w a s u sed to o p tim iz e the y ie ld of

tr ia z e n e . The 4 -n itr o p h e n y l d e r iv a t iv e i s m o re r e a c t iv e due to the e le c tr o nw ith d raw in g e f fe c t of the n itro grou p . R ea c tio n of T E A N w ith a tw o -fo ld

oe x c e s s of 4 -n itr o p h e n y l iso c y a n a te in a c e to n it r i le a t 0 C gave in sta n ta n eo u s fo r m a tio n of a d eep p u rp le so lu tio n . P r o t ic w o rk -u p and colum n ch ro m a to g ra p h y gave a 65% y ie ld of 1 ,3 - b i s (4 -n itro p h e n y l) tr ia z e n e (5 0 ).

T hus fo r m a tio n of the tr ia z e n e a p p ea red to be the m ajor r e a c tio n p ath w ay. A r e a so n a b le m e c h a n ism can be p r o p o se d fo r the tr a n sfo r m a tio n (S ch em e 4 2 ). I n it ia lly n u c le o p h ilic a tta ck of the n itr ite ion on the a c y l carb on a to m of the iso c y a n a te m o ie ty p ro d u ces the a n ion (51 ). N itr ite io n a tta ck s a s an o x y g en cen tred n u c le o p h ile , the h a r d e r of the two p o te n tia l s i t e s , on the r e la t iv e ly h ard ca rb on a to m of the h e ter o cu m u le n e s y s te m . The a n io n ic in te r m e d ia te (51) m u st r e a r r a n g e by m ean s of m ig r a tio n of the n itr o s o group fr o m oxy g en to n itr o g e n to g ive (52 ).F a c i le lo s s o f ca rb o n d io x id e th en p ro d u c es the d ia z o ta te (53), w h ich in the p r e s e n c e o f fu r th e r iso c y a n a te w il l i t s e l f r e a c t to g iv e the secon d a n io n ic adduct (5 4 ). A g a in th is adduct can r e a r r a n g e by m ean s of m ig r a tio n of the 4 -n itr o p h e n y l d ia zo group fr o m o x y g en to n itro g en to g iv e (55 ). A se c o n d lo s s of ca rb o n d io x id e p r o d u c e s the anion of the tr ia z e n e (56 ). T h is a n ion (56) is v e r y s ta b le due to the e x te n s iv e

g . . .d e lo c a liz a t io n o f the n eg a tiv e ch a rg e o v e r both a r o m a tic r in g s . A n ion (56) i s the d eep p u rp le s p e c ie s o b se r v e d in so lu t io n . F in a lly p r o tic w o rk -u p g iv e s the tr ia z e n e .

T he 4 -n i t r o group h as a m a jo r e f fe c t on the r e a c t io n and p ro d u c es a h ig h er y ie ld o f tr ia z e n e . F ir s t ly the co n ju g a tiv e e f fe c t of the n itro group s t a b i l iz e s a l l of the a n io n ic in te r m e d ia te s , in p a r tic u la r the d ia z o ta te (53 ). S ec o n d ly , e le c tr o n w ith d ra w a l by the n itro group in c r e a s e s r e a c t iv ity of the a c y l ca rb on a to m w h ich le a d s to m o r e e f f ic ie n t trap p in g o f the d ia z o ta te to g iv e the tr ia z e n e . T h ird ly , the tr ia z e n e an ion (56) i s , i t s e l f , h ig h ly s ta b il iz e d .

(50)

- 34

N O , - / V n = C = 0'

- 7 W \

Et4 N ® 0 = N — 0®

f \ M eCN/ 0°C

SCHEM E 42

- 3 5

The r e a c t io n of S ch em e 42 i s rem a rk a b le in s o fa r a s n itr o sa tio nh as b een b rough t about under v e r y m ild co n d itio n s u s in g n itr ite ion in ano rg a n ic so lv e n t a t 0 °C . The n itr o sa t io n o c c u r s in an in tr a m o le c u la rfa sh io n a fter the n itr ite ion has b een a c tiv a te d to a n itr o sa tin g agen t bythe in it ia l r e a c t io n w ith the anh yd rid e.

The y ie ld o f tr ia z e n e w as then o p tim ize d . T he e x c e s s of iso c y a n a tew a s v a r ie d and the y ie ld of tr ia z e n e m e a su r e d u s in g r e v e r s e p h ase h p lc .C o n ce n tr a tio n s w e r e d eterm in ed by c o m p a r iso n w ith stan dard so lu tio n so f the a u th en tic 1 , 3 -b is (4 -n itr o p h e n y l) tr ia z e n e p r e p a r e d by another

94m eth o d .T he r e s u lt s a r e g iv en in T ab le 1, and sh ow a m a x im u m y ie ld of

85% w ith a te n -fo ld e x c e s s of the iso c y a n a te o v er n itr ite ion . The y ie ld in c r e a s e s w ith th e e x c e s s of iso c y a n a te , p r e su m a b ly b ec a u se of m o re e f f ic ie n t trap p in g of the d ia zo ta te io n . H ow ever th e re is an optim um b e c a u se w ith v e r y la r g e am ounts of is o c y a n a te , tr im e r iz a t io n b e c o m e s s ig n if ic a n t . T h is e x p la in s the d e c r e a s e d tr ia z e n e y ie ld w ith g r e a te r th an 1 0-fo ld e x c e s s .

oR ea c tio n at h ig h er te m p er a tu r e (37 C) sh ow ed a redu ced y ie ld , p ro b a b ly b e c a u se of the in s ta b ility o f the d ia zo ta te in te r m e d ia te .T A B L E 1 : O p tim iza tio n of the y ie ld o f 1 . 3 -b is (4 -n itr o p h e n y l)

tr ia z e n e fr o m r e a c tio n of e x c e s s 4 -n itr o p h e n y l is o c y a n a tea oand n itr ite in a c e to n itr i le at 0 C.

RATIO - l f i NCQJ--------[n ° 2 -]

T R IA Z E N E YIELD / %

1 462 655 818 84

+ b10 85 - 220 7010 2 3 °

a - b - c -

[t E A n ] = 2 -5 X 10“ 3 m o l d m " 3 A v e r a g e o f th r e e r e a c tio n s A t 3 7 ° C

- 36 -

2 . 6 E V ID E N C E FOR PRO POSED M ECHANISMThe m e c h a n is m p ro p o sed fo r the fo r m a tio n of the tr ia z e n e

r e q u ir e d v e r if ic a t io n and c o n firm a to ry ev id en c e w as th e r e fo r e sou gh t.2 . 6 . 1 E v o lu tio n of C arbon D io x id e

In the r e a c t io n outlined in S ch em e 4 2 , two m o le s o f carb on d io x id e a r e r e le a s e d fo r e v e r y m o le of tr ia z e n e fo r m e d . No ob v iou s ev o lu tio n o f g a s i . e . b u b b les , i s o b se r v e d , but w h en n itr o g e n i s bubbled through the r e a c t io n so lu tio n the efflu en t g a s e s tu rn l im e w a ter tu rb id .2 . 6. 2 D e te c t io n o f D ia zota te

A c c o r d in g to S ch em e 4 2 , the d ia z o ta te in te r m e d ia te shou ld be ob ta in ed fo r r e a c t io n s w ith e x c e s s n itr ite ion o v er is o c y a n a te . The d ia z o ta te w a s th e r e fo r e trapped and the y ie ld d e te r m in e d .

The m eth od of a n a ly s is for the d ia z o ta te in v o lv ed d ilu tio n of the r e a c t io n so lu tio n in to aqueous 0. IN b o ra x (pH 9) co n ta in in g e x c e s s 2 -n a p h th o l-3 ,6 -d is u lp h o n ic acid (5 7 , R -S a lt ) . T h is ca u se d h y d r o ly s is o f the d ia z o ta te to the d iazon iu m io n , w h ich w as trap p ed by the R -S a lt

s p e c tr o p h o to m e tr ic a l ly . The a s s a y w a s c a lib r a te d u s in g so lu tio n s o f th e d ia z o n iu m io n fo r m e d in s itu by tr e a t in g the c o r r e sp o n d in g am in e w ith n itr o u s a c id .

U sin g th is m eth od the 4 -n itr o p h e n y l d ia zo ta te w a s d e tec te d in a m a x im u m y ie ld o f 72% w ith a 5 0 -fo ld e x c e s s o f n itr ite io n (T ab le 2).T he y ie ld w as o b se r v e d to in c r e a se w ith the e x c e s s o f n itr ite io n a s th is m in im iz e d co m p e tin g d im e r iz a tio n , tr im e r iz a t io n and fu r th er r e a c t io n s o f the d ia z o ta te .

The r e s u l t s c o n fir m that the d ia z o ta te i s an in te r m e d ia te in the fo r m a t io n of t r ia z e n e .

- 37 -

T A B L E 2: Y ie ld s of D ia zo ta te fr o m r e a c tio n o f e x c e s s TEAN w ith3r O4 -n itr o p h e n y liso c y a n a te in a c e to n itr i le at 0 C

RATIO - [t e a n ] D IA Z O T A T E Y IE L D / %[r n c o ]

5 4519 6024 6350 72

a - [RNCO ] c a . 4 x lO m ol dm

2. 6 . 3 R e a c tio n of D ia zo ta te w ith Iso c y a n a teThe 4 -n itr o p h e n y ld ia z o ta te i s the m o s t sta b le of the a ro m a tic

d ia z o ta te s due to i t s h igh le v e l of con ju g a tio n (S ch em e 4 4 ) . T h is a llo w s th e p r e p a r a tio n and iso la t io n of the so d iu m sa lt a s a c r y s ta l l in e s o l id .The is o la te d d ia z o ta te w as th e r e fo r e r e a c te d w ith the iso c y a n a te in o r d e r to in d ep en d en tly d em o n stra te the se c o n d step of the r e a c t io n in S ch e m e 4 2 . A b e s t y ie ld o f 85% w as obtained w ith a 2 0 -fo ld e x c e s s o f iso c y a n a te (T a b le 3).

SCHEM E 44T A B L E 3: Y ie ld s of tr ia z e n e fr o m r e a c tio n o f e x c e s s 4 -n itr o p h e n y l

aiso c y a n a te w ith so d iu m 4 -n itr o p h e n y l d ia z o ta te in a c e to n itr ile a t 0°C

RATIO [r n c c J[d ia z o t a t e ^TRIAZENE YIELD/ %

5 4010 70 t 5b20 85 t 5b30 80

a - [D IA Z O T A T E ] = 2. 5 x 10‘ 3 m o l d m b - a v e r a g e of 3 runs

- 38 -

The la r g e e x c e s s req u ired s u g g e s t s that r e a c t iv ity of the d ia z o ta te to w a rd s 4 -n itr o p h e n y l iso c y a n a te i s l e s s than e x p e c te d . T h is m a y be due h o w ev e r to the u se of the so d iu m s a l t o f the d ia z o ta te ra th er than the te tra e th y la m m o n iu m sa lt fo r the r e a c t io n of n itr ite ion w ith the i s o c y a n a te . T he so d iu m s a lt of the d ia zo ta te i s n ot r e a d ily so lu b le and p ro b a b ly not h ig h ly d is s o c ia te d in a c e to n itr ile and co n se q u e n tly i t m a y ap p ear to be l e s s r e a c t iv e . The te tr a e th y la m m o n iu m s a lt of the d ia z o ta te w as d if f ic u lt to p r e p a r e due to i t s h y g r o s c o p ic n a tu re .

In c o n c lu s io n a l l the above e v id e n c e su p p orts the m e c h a n ism o u tlin ed in S ch em e 4 2 . A k in e t ic stu d y m ig h t h ave g iv e n added e v id e n c e and id e n tif ie d the ra te d eterm in in g s t e p , but th e r e a c t io n s a r e too fa s t e v e n at 0°C fo r s im p le ra te m e a s u r e m e n ts .2 .7 VARIATIO N OF SOLVENT

P r e lim in a r y e x p e r im e n ts w ith p h en y l iso c y a n a te in d ica ted th at s im ila r p ro d u cts w er e obta ined fr o m r e a c t io n w ith TEAN in a ran ge of s o lv e n ts i . e . a c e to n it r i le , a ce to n e and d ic h lo r o m e th a n e . A m o re d e ta ile d study of so lv e n t e f fe c ts w a s th e r e fo r e m ade w ith 4 -n itr o p h e n y l is o c y a n a te .2 .7 . 1 T etra h y d ro fu ra n (T H F )

TEAN is v ir tu a lly in so lu b le in T H F , so the te tra b u ty la m m o n iu ms a lt w as p rep a red by the sa m e m eth o d and u se d . R e a c tio n of n itr ite io n

ow ith a 5 -fo ld e x c e s s of 4 -n itr o p h e n y l iso c y a n a te in TH F at 0 C gav e a 58% y ie ld of tr ia z e n e a s d e ter m in e d by h p lc .2 . 7 . 2 D im eth y l su lp h ox id e (DM SO)

The u se o f DMSO a s so lv e n t e n a b le s so d iu m n itr ite to be u se d a s iti s r e a d ily so lu b le . In itia l r e a c t io n s gave v e r y p oo r y ie ld s of the t r ia z e n e .

9 5 ,9 6 97T h is w as found to be due to r e a c t io n o f the iso c y a n a te w ith the DM SO * ’T he so lv e n t i s s u ff ic ie n t ly n u c le o p h ilic to a tta ck th e iso c y a n a te g iv in g an in te r m e d ia te (59) w h ich u lt im a te ly y ie ld s d im e r s , t r im e r s and tw o o th e r p ro d u c ts (60) and (61) con ta in in g a s o lv e n t m o le c u le (S ch em e 4 5 ) .

R ea c tio n s w ere th e r e fo r e c a r r ie d out w ith a so lu tio n of 4 -n itr o p h e n y l is o c y a n a te in a s m a ll am ount o f a c e to n it r i le (5 m l) and adding th is to a so lu t io n of so d iu m n itr ite (10 m g) in DMSO (10 m l) at 0 °C . A n 80% y ie ld of tr ia z e n e w as a ch iev e d w ith a 1 0 - fo ld e x c e s s o f is o c y a n a te . U n d er

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R— N = C ==0 + "0- K J O

/CH3 0■ R

\ h3 © \

t k CH>

Q

R — N 0I

n^ S\ ^ CH3I LHjR 3

(60)

R— N = S/\

CH'

CH:

(61)

SC H EM E 4 5

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id e n t ic a l co n d itio n s the so d iu m d ia z o ta te rea c ted w ith the iso c y a n a te to g iv e a 64% y ie ld o f tr ia z e n e .

So the r e a c t io n i s not s p e c ia l to the T E A N -A c e to n itr ile s y s te m and m a y be c a r r ie d out in o th er s o lv e n ts w ith v a ry in g d e g r e e s of s u c c e s s .2 . 8 VARIATIO N OF ISOCYANATE STR U C TU R E2 .8 .1 P h e n y l I so c y a n a te

W hen good y ie ld s o f tr ia z e n e w e r e obtained fr o m 4 -n itr o p h e n y l is o c y a n a te , the r e a c t io n of the p h en y l d e r iv a tiv e w a s r e -e x a m in e d . U sin g th e h p lc a s s a y , the y ie ld of 1 ,3 -d ip h e n y l tr ia z e n e w a s o p tim ized (T a b le 4) and found to be 9 0 - 5% w ith a 3 0 -fo ld e x c e s s of iso c y a n a te o v er n itr i t e . The g r e a te r e x c e s s r e q u ir e d r e f le c t s the lo w e r r e a c t iv ity of th e p h en y l iso c y a n a te and th e r e fo r e the l e s s e f f ic ie n t trap p in g of the d ia z o ta te . I n c r e a s e in the r e a c tio n tem p er a tu r e red u ced the y ie ld o f tr ia z e n e p ro b a b ly b e c a u se of the in s ta b il i ty of the p h en y l d ia z o ta te . A s im ila r e ffe c t w a s n oted fo r the 4 -n itr o p h e n y l iso c y a n a te (T ab le 1).T A B L E 4 : Y ie ld s o f 1 ,3 -d ip h e n y ltr ia z e n e fr o m r e a c t io n o f e x c e s s

p h en y l iso c y a n a te and TE A N 3- in a c e to n it r i le at 0°C

[r n c o ] T R IA Z E N E YIELD / %KA 1[n ° 2 ‘ ]

10 4 3 , 4620 54_ Ab 20 1725 5730 9 0 - 553 59

a - [NO^ ] = 2 -5 x 10 ̂ m o l d mb - A t 25°C c - A v e r a g e o f 4 run s

The r e a c t io n in w a ter w as th e r e fo r e r e -e x a m in e d . R ea c tio n of0 .4 6 M p h en y l is o c y a n a te and 1 .0 M so d iu m n itr ite at ro o m te m p e r a tu r e g a v e a 2% y ie ld o f t r ia z e n e . W ith e x c e s s iso c y a n a te ( [phNCo] = 0 .4 6 M)

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and a d e f ic ie n c y o f n itr i te ( [ NO^ ] = 0 . 073 M) the y ie ld w as 8%. So then itr ite ion w ill c o m p e te w ith w a ter fo r the iso cy a n a te to g iv e m e a su r a b le a m ou n ts of t r ia z e n e .2 . 8 . 2 O ther 4 -s u b s t itu te d P h en y l Iso cy a n a te s

S e v e r a l 4 -s u b s t itu te d p henyl is o c y a n a te s w er e ex a m in ed to probeth e e ffe c t of su b st itu e n ts on the r e a c t io n . The c o r r e sp o n d in g 1 ,3 - d ia r y l -

94tr ia z e n e s w ere p re p a r e d by a l ite r a tu r e m ethod and u sed a s stan d a rd s fo r the hplc a s s a y .

-f4 -M eth y lp h en y l iso c y a n a te g a v e an optim um y ie ld o f (60 - 3)% in a c e to n itr i le at 0 °C , w ith a 3 0 -fo ld e x c e s s of iso c y a n a te (T a b le 5).C o o lin g the r e a c t io n to -4 0 °C d e c r e a s e d the y ie ld . 4 -C h lo r o p h e n y l iso c y a n a te gave an o p tim u m y ie ld o f 6 5 - 5% w ith a 2 0 -fo ld e x c e s s of su b s tr a te under the s a m e con d itio n s (T ab le 6). The b e s t tem p er a tu r e fo r th e se r e a c tio n s a p p ea red to be 0°C and so fu r th er o p tim iza tio n r e a c t io n s w ere c a r r ie d out at th is te m p e r a tu r e .

4 -T r if lu o r o m e th y lp h e n y l iso c y a n a te gave a b e s t y ie ld of 63—10% w ith a ten -fo ld e x c e s s o f su b str a te , and the 4 -m e th o x y p h e n y l iso c y a n a te g a v e an optim u m o f 20% w ith a 5 0 -fo ld e x c e s s of s u b s tr a te . T h e se data a r e su m m a r ize d in T a b le 7.T A B L E 5: Y ie ld s o f T r ia z e n e fr o m rea c tio n o f e x c e s s 4 -M eth y lp h en y l

a ois o c y a n a te w ith T E A N in A c e to n itr ile a t 0 C

RATIO J r n c o L TRIAZENE Y IELD / %[n ° 2 -]

15 5530 63 , 573 0 b 2860 23

a - [NO ̂ ] = 2 - 5 x 1 0 ̂ m o l dm b - D one at -4 0 °C

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T A B L E 6: Y ie ld s o f T r ia zen e fr o m r e a c tio n o f e x c e s s 4 -C h lo r o p h en y lis o c y a n a te and TEAN a in A c e to n itr i le a t 0°C

RATIO[N ° 2 -]

T R IA Z E N E Y IELD / %

10 60 t 520 6 5 - 528 4 230 4 7 , 52

a - [NC>Z ] = 2 -5 x 10 m o l dm

T A B L E 7: O p tim u m T r ia zen e y ie ld s fo r r e a c t io n o f e x c e s s a ro m a ticis o c y a n a te s and te tr a e th y la m m o n iu m n itr ite in

oa c e to n it r i le at 0 C

2 .8 . 3 E ffe c t o f su b st itu e n ts

The y ie ld s g iv e n in Table 7, sh ow that fo r m a tio n of the 1 ,3 - d ia r y l - t r ia z e n e is fa v o u red by e le c t io n w ith draw in g 4 - s u b s t itu e n t s . The lo w e s t y ie ld i s obta ined w ith the e le c tr o n donating 4 -m e th o x y su b stitu en t.

Two e f fe c t s p ro b a b ly con tr ib u te to the o b se r v e d tren d .1. The e le c tr o n w ith d raw in g su b stitu en ts ( e s p e c ia l ly th o se w ith a g r e a te r r e so n a n c e e f fe c t ) , s ta b il iz e the a n io n ic in te r m e d ia te s , in p a r t ic u la r the d ia z o ta te .

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2 . E le c tr o n w ith d raw in g su b stitu en ts in c r e a s e the r e a c t iv ity of theiso c y a n a te m o ie ty by in c r e a s in g the e le c tr o n d e f ic ie n c y o f the a c y l ca r b o na to m . Thus the iso c y a n a te w ill trap out the d ia z o ta te m o re e f f e c t iv e ly .

A m o d era te c o r r e la t io n e x is t s b etw een log (m a x . y ie ld ) and the98su b stitu en t c o n s ta n ts , (F ig . 1) a lth ou gh the p h en y l su b stra te g iv e s a

h ig h e r y ie ld and the 4 -c h lo r o p h e n y l su b str a te a lo w e r y ie ld than e x p e c te d . T he c o r r e la t io n i s p er tu rb ed by the fa c t that the o p tim u m y ie ld s r e q u ir e d iffe r e n t e x c e s s e s of iso c y a n a te o v e r n itr ite ion , due to the co m p etin g tr im e r iz a t io n r e a c t io n . S ub stitu en t c o n sta n ts a re n o r m a lly u sed to c o r r e la te r a te s of r e a c tio n not p rod u ct y ie ld s , and the in h eren t d if f e r e n c e s in the two ty p es o f m e a su r e m e n t w ould be e x p e c ted to r e s u lt in a p o o r e r c o r r e la t io n w ith p ro d u ct y ie ld s . T he s lo p e o f the p lo t ( ^0= + 0 . 55) in d ic a te s that the r e a c t io n is fa v o u red by e le c tr o n w ith d ra w a l.

The d ia z o ta te y ie ld s exh ib it s im ila r b eh a v iou r to that o b se r v e d fo r the t r ia z e n e s . (T a b le 8 ). T hus the s ta b il ity of the d ia zo ta te i s o f p aram ou n t im p o r ta n c e to the s u c c e s s o f the r e a c tio n .T A B L E 8: Y ie ld s of D ia zo ta te fr o m r e a c tio n o f a ro m a tic is o c y a n a te s

ow ith a 5 0 -fo ld e x c e s s o f T E A N in A c e to n itr i le at 0 C

2 .9 CONCLUDING REM ARKSIt has b een d em o n str a ted that a r o m a tic is o c y a n a te s w ill r e a c t

w ith n itr ite ion u n d er m ild co n d itio n s to g iv e good y ie ld s of the 1 ,3 -d ia r y l t r ia z e n e s . T hus n itr o sa t io n i s o b se r v e d to take p la c e a s a r e s u lt of the a c t iv a tio n of the n itr ite by its r e a c tio n w ith the a n h y d r id e . The r e a c t io n i s s im ila r to that o b se r v e d w hen N -n itr o s a m in e s a r e p rod u ced fr o m r e a c t io n of n itr ite w ith im in iu m ca t io n s ( s e e S e c tio n 1 .3 .4 ) .

The r e a c t io n is a m ild e r m eth od fo r the fo r m a tio n of t r ia z e n e s th an the u su a l s y n th e s e s under a c id ic c o n d it io n s . F o r com pounds w ith e le c tr o n w ith d raw in g su b st itu e n ts , the y ie ld s a re co m p a ra b le to th o s e o f

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F IG . 1 G raph o f lo g (m axim u m y ie ld ) v e r s u s ^~R fo r F o rm a tio nof 1 , 3 -D ia r y ltr ia z e n e s fr o m R ea c tio n of 4 -S u b stitu ted P h e n y l I so c y a n a te s and N itr ite Ion in A c e to n itr i le a t 0°C

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p r e v io u s s y n t h e s e s , a lthough p u r if ic a t io n i s c o m p lic a te d by the b y p ro d u c ts fo rm ed fr o m the e x c e s s is o c y a n a te on w o rk -u p .

It i s in te r e s t in g that the tr ia z e n e a n ion s fo rm ed do not r e a c tfu r th e r w ith the is o c y a n a te s , a lth ou gh the r e a c tio n o f p ro to n a ted t r ia z e n e s

9 9h a s b een stu d ied . D e lo c a liz a t io n o f the ch a rge m u st r e s u lt in g r e a t ly red u ced n u c le o p h ilic ity . W here th e r e i s l e s s d e lo c a liz a t io n of n eg a tiv e c h a r g e , m o re tr ia z e n e m ay be lo s t by fu r th er r e a c t io n . Thus the s o f te r b a s e s r e a c t l e s s r e a d ily w ith the h ard iso c y a n a te c e n tr e . T h is g iv e s a n o th er p o s s ib le r e a s o n fo r the low y ie ld obta ined fr o m 4 -m e th o x y p h e n y l i s o c y a n a te .

The r e a c t io n a ls o o ffe r s a m ild s y n th e s is of a zo d y e s . T h is i s e x e m p lif ie d in the c o lo r im e tr ic t e s t u sed to d e te r m in e the d ia zo ta te y ie ld s . R e a c tio n o f e x c e s s n itr ite io n w ith a r o m a tic iso c y a n a te g iv e s an o rg a n ic so lu tio n o f the d ia z o ta te , w h ich m ay be trap p ed w ith a ran ge of a r o m a tic com p ou n d s su ch a s 2 -n a p h th o l-3 , 6 -d isu lp h o n ic a c id , to g iv e an a z o com p ou nd . U su a l m eth od s o f a z o d ye fo r m a tio n in v o lv e d ia z o t iz a t io n in co n c en tr a te d a c id so lu tio n . In in d u str y d is p o s a l o f the a cid r e s id u e s i s a m a jo r p r o b le m . T h is m ethod w ou ld g iv e a rou te a vo id in g c o n c e n tr a te d a c id and fo r th is r e a so n could h ave c o m m e r c ia l a p p lic a t io n s . I s o c y a n a te s a r e m ade in la r g e q u a n titie s fo r the p o ly m e r in d u stry , so the te c h n o lo g y fo r th e ir in d u s tr ia l s c a le p ro d u ction is w e ll known.

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CHAPTER 3

REACTION OF NITRITE ION WITH ALKYL ISOCYANATES

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3. 1 INTRODUCTIONA lk y l iso c y a n a te s r e a c t w ith n u c le o p h ile s but l e s s r e a d ily than the

a r o m a tic a