y l s i l y l -p r o t e c t e d primary enamines 4 condense wlth two equivalents of phosgenimlnium chloride ( P I ) to f o r m 2-aza-1.5-dichloropentamethinecyanines 5 .These versatile intermediates cyclize upon heatzng to 2 -~d i a l k y l a m ~n o ~-5 -a 1 k y l -6 -6 1 y 1 -4 -4 h 1 0 r 0 p y i i d n e s 6 via a loss of the corresponding alkyl chloride.The reactions a r e completely r e g i o ~p e c i f i c and represent a new useful entry to p y r i m ~d ~n e nuclei.Phasgeniminlum salts (PI) a r e valuable synthons in heterocyclic chemistry because 1 -4 of thelr three mobzle chlorine atoms .Thls is even more true for various trimethine and pentamethlne cyanines and for t h e ~r aza-analogues which are r e a d ~l y obtained from P I salts, usually in a single step process.Thus, for example, monosubstltuted acetonltriles or eventually the corresponding pzlmary amides condense smoothly vlth PI in the presence of hydrochloric acld t o 5 give 1 , 3 , 5 -t r l c h l o r o -2 -a 1 a P e n t a m e t h l n e cyanlnes 1 carrying a substituenteven a 8 CL Q RCH2CN R Me2N :C ' CL \ CL -HCL MD~N*N+NM~* m Q fluorine atom6 -~n the 4 -p o s l t ~o n .we notxced that upon thermolysis (120-18O0C1 one dimethylamino group acts as the internal nucleophlle thereby leading t o the 5 ring-closed products 2 via a loss of two molecules of methyl ( o r alkyl) chloride .his finding r s o f foremost importance because such a synthetic principle has not been used in the past and also because o f the multifaceted biolaglcal activities of pyrimidine n ~c l e i " ~. ~n the above case only one group R can be varied, the 4-and 6-positions being occupied by chlorine atoms.Inasmuch as a large s e r ~e s o f polysubstltuted pyrimidines w a s required in order to perform their bloloqical s c r e e n l n q , we investigated the reaction between P I salts and primary enamines 3b.It is well-known that 3b as well as their imlne tautomers 3a a r e unstable unless some specla1 features are present.s his may be for instance an electron-withdrawing group in the 8-position.9 ~o r t u n a t e l y , both forms 3a.b c a n be stabilized by silylatlnq the nitro??" atom .he tautorneric m ~x t u r e s of 4a.b are conveniently obtained in a slngle-flask reaction from n ~t r i l e s and Griqnard reagents followed by silylation of rmine salts formed in sicu.Products 4 can be distilled and it is unimportant which isomer.elther 4a or 4b,predominates i n the equillbriurn mixture for the following condensation with PI salts.This method works well w ~t h non-enollzable nitrile such as substituted benzonitriler or heteroaromatlc nltrlles e .g .2-cyanothlaphene (Table I ) .
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Guillot et al. (1989) studied this question.