With Amidines

The reaction of amidines with o-aminonitriles to give (fused) 4-amino-pyrimidines was introduced by Taylor and Ehrhart in I960.90 The reaction is thought to proceed through the more complex amidine of type 114, in which R (the methyl group of acetamidine for instance) becomes an alkyl group in the 2-position of the product. At the temperatures used, ring closure is rapid, and no intermediate such as 114 has been isolated. 

The amidine is always used as its acetate because the hydrochloride gives very little yield. It seems that the acetate is a source of free amidine. Many kinds of amidines are suitable, including lV,lV -dibutylformamidine, which 

De Wolfe, Carboxylic Ortho Acid Derivatives. Academic Press, New York, 1970. 

For most purposes, this amidine synthesis is preferable to the formamide and the ortho ester alternatives it occurs at a lower temperature than the former, and it is free from the intrusion of intermediates characteristic of the latter. It is particularly useful when an alkyl or chloroalkyl group is required in the 2-position of the product, this pathway being much less explored in the formamide and the ortho ester methods. The amidine reaction is suitable for both 7t-deficient and 7t-excessive nuclei. 

Amidines other than formamidine have been used. 4-Amino-5-cyano-1,2,3-triazole and its 1-, 2-, and 3-methyl and 3-benzyl derivatives (see 20) gave 

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Several related derivatives have also been utilized in this type of synthesis. Imino-chloromethanesulfenyl chlorides (184), prepared by the controlled addition of chlorine to isothiocyanates, react with amidines (161) to give 1,2,4-thiadiazolines (185) (71T4117). Chlorocarbonylsulfenyl chloride (186), prepared by the hydrolysis of trichloromethanesulfenyl chloride with sulfuric acid, reacted with ureas, thioureas and guanidines to give 1,2,4-thiadiazolidine derivatives (187) <70AG(E)54, 73CB3391). 

The condensation of 1,3-dicarbonyl compounds 1 with amidines 2 catalyzed by acids or bases to give pyrimidine derivatives 3 is regarded as the Pinner pyrimidine synthesis. ... 

Dibenzo[l,3]diazepines 9, together with amidines and benzimidazoles, are produced by a rearrangement reaction when certain A.A -diarylamide oximes 7 are treated with tosyl chloride. The intermediate 0-tosyl derivatives 8 cannot be isolated.176... 

Interestingly, it appears that thiirene oxides also react with amidines (e.g. DBU) in a similar way2. 

A similar strategy has been used to prepare pyrimidines, as well as pyra-zoles and isoxazoles by reacting the enamine intermediate with a variety of bidentate nucleophiles [78]. Microwave irradiation of a cyclic 1,3-diketone 49 and acetal 45 in water generated the corresponding enaminoketone 50 in situ which reacted with amidines, substituted hydrazines or hydroxylamine in only 2 min in a one-pot process to give 4-acylpyrimidines, pyrazoles or isoxazoles, respectively (Scheme 20). 

A general synthesis of pyrrolo[3,4-mediated reductive cyclisation of the pyrrolidinones 16 with amidines. The suggested mechanism is that shown in Scheme 2 < 95JOC7687 >. 

Reactions of Alkyl 4-Chloro-3-trimethylsilyloxycrotonates with Amidines to Give Alkyl lmldazole(4,5]-acetates... 

Abdou, H.E., Mohamed, A.A. and Fackler, J.P. Jr (2004) Oxidative addition of methyl iodide to dinuclear Gold(I) amidinate complex schmidbaur s breakthrough reaction revisited with amidinates. ZeitschriJiJurNaturforschungB. A Journal of Chemical Sciences, 59, 1480-1482. 

Scheme 6.4 Condensation of dihydroxyfumarate derivatives with amidines to pyrimidinone...

Alkylidenetetrahydrofurans underwent a cyclo-condensation with amidines to give 4-(3-hydroxyalkyl)pyrimidines, as can be seen below <06T5426>. 

The 1,2,4-oxadiazole dioxolanes 144 react with hydroxylamine and hydrazines to form the 5-pyrazole- and isoxazole-substituted 1,2,4-oxadiazoles 146 via the dioxolane ring-opened intermediates 145 (Scheme 17). Reaction of compounds 144 with amidine or guanidine salts allows access to pyrimidine substituted analogues 147, via intermediate 145 (X = C(NH)R1), albeit in lower yield <1996JHC1943, 1998JHC161>. 

Muller and co-workers reported the three-component one-pot synthesis of various pyrimidines through the in situ generation of unsaturated carbonyl compounds. The palladium catalyzed coupling of aryl halides bearing electron withdrawing substituents 7 with propargyl alcohols 8 produced unsaturated carbonyl compounds 9 after isomerization, which condensed with amidines 10 to form triaryl pyrimidines 11 . 

The condensation of diethyl formylsuccinate with amidines is an established p3mmidine synthesis (16, 714). Extended to 1-substituted biguanides, the reaction yields 2-guanidino-4-hydroxy-5-carbethoxy-methylpyrimidines as follows (684) ... 

N Content in Amidines and in Products Obtained in the Reaction of 5-Nitropyrimidines with Amidines... 

The even greater basicity of guanidine (p/iLa = 13-6) as compared with amidines is due to an even greater resonance stabilization of the cation, since three equivalent resonance structures enter into resonance [6]. The base itself resonates between three nonequivalent structures [37], and has according to Pauling (1939,... 

The reaction of a-halogenoximes 126 with amidines in the presence of iron carbonyls gives imidazoles 127 in 31-79% yields. The reaction occurred via deoxygenation of 4H-1,2,5-oxadiazines by iron carbonyls (equation 55). Efficiency of carbonyls decreased in the following order Fe3(CO)i2 > Fe2(CO)9 > Fe(Co)5 . ... 

Malonaldehyde is unstable and is therefore used as its diacetal, 1,1,3,3-tetramethoxypropane 641, in reactions with amidine hydrochlorides 642. Reaction occurs best in a sealed tube at 175 °C <1997SC2521>. 

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