Cyanoacetate, bromo, reaction with

The chlorine groups in 4-chloro-1,10-phenanthroline and 4,7-dichloro-1,10-phenanthroline are replaced by cyano groups on fusion with potassium cyanide while 2-cyano- and 5-cyano-1,10-phenanthrolines have been obtained from 2-chloro and 5-bromo-1,10-phenanthrolines, respectively, by reaction with cuprous cyanide. 2-Chloro-1,10-phenanthroline (69) reacts with the sodium salt of tert-butyl cyanoacetate to give the intermediate 105, which with cold hydrochloric acid affords 2-cyanomethyl-1,10-phenanthroline (106). 2-Chloro-1,10-phenanthroline also participates in the Ullmann reaction to afford 2,2 -bi-( 1,10-phenanthroline) (107). 5,5 -Bi-(l,10-phenanthroline) was also prepared, but by a different route starting from 8,8 -diamino-6,6 -biquinoline. 

Alkylation and Arylation. The 5-methylation of thioamides by diazomethane is catalysed by silica gel. 5-Phenyl derivatives of thiobenzanilides are obtained in high yield by radical arylation with nitrosoacetanilide or phenylazotriphenyl-methane. Thiols are made from alkyl (or cycloalkyl, or aralkyl) halides by their reaction with dimethylthioformamide and treatment of the imidium ester with methanol other methods of hydrolysis lead to side-reactions, giving impure products. Mono- and bi-protic thiocarboxamides condense with ethyl bromo-cyanoacetate and one equivalent of NaOEt with spontaneous separation of sulphur and the formation of ff-amino-cr-cyano-acrylates, as shown in reaction (5). The... 

Copper and copper salts also mediate transfer of an alkoxycarbonyl(cyano)methylene unit from a-bromo-a-cyanoacetic esters to certain halogenated 1,3-dienes, e.g. formation of This reaction, which has been carried out with various modifications (including the use of ethyl a-chloro-(x-cyanoacetate), gives access to the acid component of several pyrethroid insecticides. In mechanistic terms, a radical 1,2-addition of the a-halogenated ester to the alkene followed by dehydrohalogenative cyclization takes place (cf. Houben-Weyl Vol.4/3, p369). 

Later, the same research group [101, have reported on synthesis of two 5-bromo substituted 2-aminothiophenes 35 (Table 10) via a two-step Gewald synthesis. In a reaction of 3-trifluoromethylacetophenone (30) with either benzoylacetonitrile or ethyl cyanoacetate (31) in the presence titanium(IV) chloride [102] afforded Knoevenagel-Cope product 32. In subsequent treatment of 32 with sulfur the 2-aminothiophene core 33 is formed under basic conditions. The free C-5 position of derivative 33 is substituted with bromine in two following steps - first the free amino group is being Boc protected and then C-5 position brominated with A-bromosuccinimide (Scheme 16) [101]. 

The photoinitiated reactions of 2-bromobenzonitrile and 2-bromo-3-cyano-pyridine with the carbanion of ethyl cyanoacetate afford the substitution product in good yields (90 and 80%, respectively) by an SrnI process. On the other hand, a non-chain radical nucleophilic mechanism is proposed to occur in the almost quantitative substitution of o-Cl, o-Br, and P-O2NQH4X (F, Cl, Br, I) with this anion in... 

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