Formamides cyano

Having a cyano group and an amino group ortho to each other on a ring is another system that has led to the formation of fused pyrimidine ring systems. In this case, an aminopyrimidine is the result. Compound 42 in Scheme 5 is one such structure. Treatment of 42a with formamide leads to the amino derivative 43 <1999PS(155)175>. Alternatively 42b provides 44 after treatment with triethyl orthoformate followed by hydrazine <1999PS(155)175>. 

A further example of the formation of a fused pyrimidine by reaction of ortho amino/cyano groups is illustrated by condensation of 2-amino-4-(4-nitrophenyl)-3-thiophenecarbonitrile with formamide in the presence of PhsP at elevated temperature <2006T11311>. 

For ammonia and primary amines there are two possible pathways, but when secondary amines are involved, only the hydrogenolysis pathway is possible. Other reducing agents167 can be used instead of hydrogen and a catalyst, among them zinc and HCI, sodium cyano-borohydride NaBHjCN,168 sodium triacetoxyborohydride,169 sodium borohydride,170 iron pentacarbonyl and alcoholic KOH,171 BH -pyridine,172 and formic acid. When the last is used, the process is called the Wallach reaction. In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Eschweiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid,173 or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction, and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be N-ethylated (e.g., ArNHR —< ArNREt) by treatment with NaBH4 in acetic acid.175... 

The use of formamide as solvent in the ammonolysis of activated aryl chlorides has been recommended when the substrate carries cyano ring substituents which can undergo hydrolysis in water.126... 

Nitrogen trifluoride Difluoramine Nitrous acid Nitric acid Cyano fluoride Formyl fluoride Carbonyl fluoride Acetyl fluoride Acetyl cyanide Isocyanic acid Methyl isocyanate Formamide Nitromethane Nitrobenzene... 

Primary and secondary alkylamines have been used for the preparation of iV-alkyl- and V,lV-dialkylcyanothio-formamides, respectively, in the reaction with 4-chloro-l,2,3-dithiazole-5-thione 41 (Equation 20) <1996TL3709>. 4-Chloro-l,2,3-dithiazole-5-one 99 in the reaction with mono- and di-alkylamines afforded N,N -disubstituted ureas in moderate to good yields (Equation 21) <2001TL8197>. The reaction was proposed to be similar to the corresponding thione 41 but displacement of a cyano group by another molecule of alkylamine accompanies this conversion. 

This synthesis involves Michael cycloaddition reaction of the readily available 4-hydroxycoumarine 1 with a cyanocrotonitrile 2 in ethanolic piperidine to afforded 2-amino-3-cyano-4-methyl-4H, 5H-pyrano-benzopyran-5-one (3). Treatment of 3 with acetic anhydride for 0.5 h and/or 3 h under reflux afforded N-acetyl and [l]benzopyrano[3/,4/ 5,6]pyrano(2,3-d) pyrimidine-6,8-dione derivatives (4) and (5a), respectively. Also, interaction of 3 with benzoyl chloride or formic acid gave the corresponding pyrimidine derivatives (5b,c) while its treatment with formamide afforded the aminopyrimi-dine derivative (6). 

If 4-aminothieno[2,3- ]pyrimidines are desired, the simplest approach is to use a 3-cyano-thiophene as precursor. Formamide or triethylorthoformate are commonly used to convert the amine (270 R1 = H) into the thienopyrimidine (271 R1 = H) (Equation (94)) <88JPR585>. The use of formic acid has been reported to give the 4-oxo compound instead <92MI 707-04). Guanidine reacts with the thiophene (270 R1 = H) to give only a 24% yield of product (271 R1 = NH2) <90HCA797>. 

The anion 19 or 20 has most generally been prepared by removal of the hydrogen bonded to a carbon a to the cyano group by a base such as phenyllithium in ether-dioxan at —10 to — 20° or by a base such as sodium hydride at the temperature of refluxing xylene. Recent work, however, has shown that these anions can be generated and caused to react at room temperature by use of sodium hydride in dimethyl-formamide. " ... 

A mixture of l-[2-cyano-2-(phenyldiazenyl)acetyl]guanidine, (93.2 g, 0.4 mol), formamide (91 g, 1.7 mol), and Raney nickel (14 g) was placed in an autoclave and allowed to react with stirring under 30 kgem" of initial pressure at 150-155 °C for 5 h. After removal of the catalyst by filtration under cooling, the filtrate was concentrated under reduced pressure. The residue was dissolved in 5% aq NaOH and an insoluble material was filtered off. This alkaline solution was acidified with HCl to give a powder yield 52g(86%) mp > 300°C. 

Biosphorus trichloride alone (793), or more recently in tetrahydrofuran or dimethyl formamide, has been used in the deoxygenation of 2-methyl-3-piperidino-pyrazine 1-oxide (793), 2-amino-3[Pg.243]

Related reactions include the formation of the 2-cyano compounds (190) when 1,2-dimethyl-5-nitroimidazole is heated with nitrosyl chloride or an AT-oxide, and when 2-methyl-l-(o-nitrophenyl)imidazoles (191) cyclize under the influence of iron(II) oxalate (Scheme 98) (74JCS(P1)1970). The last reaction product is contaminated by a large amount of amine reduction product ( 64%) but there is also some cyclization with the 4-methyl isomer of (191). In the presence of trimethylamine, 2-cyanomethylbenzimidazole condenses with acetone to give the unsaturated derivative (192 Scheme 99) (77CPB3087). Neither 2-methylimidazole nor 2-methylbenzimidazole reacts with formamide in the presence of phosphoryl chloride. 

Analogously to conventional reactions 201-203), bis(trimethylsiloxy) alkenes form heterocycles of different classes l,2-bis(trimethylsiloxy)-l-cyclohexene (305) reacts with formamide urea malodinitrile and ethyl (J-amino-crotonate to afford 4,5,6,7-tetrahydrobenzunidazole (309) ° 2-oxo-l, 3,4,5,6,7-hexahydrobenzimidazoIe (317) , 2-aniino-3-cyano-4,5,6,7-tetra-hydro-coumarone (312) and 2-methyl-3-ethoxy-carbonyl-4,5,6,7-tetrahydro-in-dole (373) respectively. 

Cumulenes Methyllithium. Sodium amide. Zinc dust. w-Cyano acids Formamide. 

Synthesis of m-cyano acids. Wasserman and Druckrey8-9 developed a novel method for the preparation of cu-cyano acids (IV), involving in the first step condensation of a cyclic acyloin (I, x — 4, 5, 6, and 10) with formamide in an acidic... 

A fivefold excess of formamide at about 145 C in a stream of ammonia converts the 2-cyano ketone (32.1) efficiently into a fused 4-aminopyrimidine. 

---