Amidines and Related Compounds

Overwhelmingly dominant tautomer so statistical correction not required. 

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The oxidation of thioacyl amidines and related compounds is a versatile ring-forming reaction which can furnish a range of 3- and 5-substituted 1,2,4-thiadiazoles (see Section 5.08.9.4). Other ring-forming reactions that can give specific types of derivatives are discussed in the following sections. 

The general topic of the basicity of amidines has been recently covered in a chapter74 in the book The Chemistry of Amidines and Related Compounds. Here, the general scheme rationalizing the dependence of basicity on the nature of the substituents is outlined. 

TABLE 13. Acidities of amidines and related compounds in DMSO... 

In a detailed study, the scope and limitations of the Diels-Alder reaction of amidines and related compounds with 1,3,5-triazines arc discussed.10 The reactions with the amidine hydrochlorides 15 (X = NH2) are best conducted at temperatures of 90-100 °C and in polar aprotic solvents (particularly in dimethylformamide). As expected for inverse electron demand Diels-Alder reactions, the reaction exhibits characteristic 1,3,5-triazine substituent effects (C02Et >HI> SMe). Thioimidates, e.g. 15 (X — SMe), undergo a similar reaction with 1,3,5-tri-azines with varying yields and competing amine or thiol elimination while imidates, e.g. 15 (X = OMe) are unreactive under the examined reaction conditions.10... 

Hafelinger, G. and Kuske, F.K.H. (1991) General and theoretical aspects of amidines and related compounds, in The chemistry of amidines and imidates, Vol. 2 (ed. S. Patai and Z. Rappoport), John Wiley Sons Ltd, Chichester, pp. 3-100. 

J. Oszczapowicz, in The Chemistry of Amidines and Related Compounds (Eds. S. Patai and... 

The other main reaction in this class is the Dieckmann-type cyclization of the intermediates (163) from 4(6)-halo-5-ethoxycarbonylpyrimidines with AC-substituted /3-alanine esters and nitriles, and related compounds, to give 5,6,7,8-tetrahydro-5-oxopyrido[2,3-[Pg.221]

Almost accidentally, Bienayme and Bouzid discovered that heterocyclic amidines 9-76 as 2-amino-pyridines and 2-amino-pyrimidines can participate in an acid-catalyzed three-component reachon with aldehydes and isocyanides, providing 3-amino-imidazo[l,2-a]pyridines as well as the corresponding pyrimidines and related compounds 9-78 (Scheme 9.15) [55]. In this reachon, electron-rich or -poor (hetero)aromatic and even sterically hindered aliphatic aldehydes can be used with good results. A reasonable rahonale for the formation of 9-78 involves a non-con-certed [4+1] cycloaddition between the isocyanide and the intermediate iminium ion 9-77, followed by a [1,3] hydride shift. 

This summary of the physiologically active amidine and guanidine compounds clearly establishes the biological versatility of these related chemical groups. Many of the compounds have given temporarry excitement to their discoverers and then been dropped - the commonest experience in medicinal chemistry. However, there are important, clinically used, medicines in all the major categories of therapeutic action discussed in the review. 

Dithiins and Related Compounds.—Diacetylenic sulphides react with Na2X (X = S, Se, or Te) to give the mono- and di-substituted heterocycles (24). Other syntheses of 1,4-dithiins from acetylenes are the reactions of amidines of phenylpropiolic acid with sulphur (or selenium) in DMF, and of dimethyl acetylenedicarboxylate with hydrogen bromide in liquid sulphur dioxide. In the latter reaction, sulphuric acid is formed by disproportionation. 

Several patents dealing with the use of volatile metal amidinate complexes in MOCVD or ALD processes have appeared in the literature.The use of volatile amidinato complexes of Al, Ga, and In in the chemical vapor deposition of the respective nitrides has been reported. For example, [PhC(NPh)2]2GaMe was prepared in 68% yield from GaMes and N,N -diphenylbenzamidine in toluene. Various samples of this and related complexes could be heated to 600 °C in N2 to give GaN. A series of homoleptic metal amidinates of the general type [MIRCfNROilnl (R = Me, Bu R = Pr, BuO has been prepared for the transition metals Ti, V, Mn, Fe, Co, Ni, Cu, Ag, and La. The types of products are summarized in Scheme 226. The new compounds were found to have properties well-suited for use as precursors for atomic layer deposition (ALD) of thin films. 

The only aspect of octopaminergic transmission for which a relatively large amount of structure-activity data is available relates to the properties of OA-receptors themselves. Agonists that stimulate these systems and antagonists that block them, are known and such compounds exist in several structural groups. The three major groups of agonists currently identified are phenylethylamines amidines and imidazolines. 

IV,N,N -Tris(trimethylsilyl)amidines have been used recently as precursors for a number of inorganic heterocycles and metallacycles,1 some of which are being studied in light of their unusual solid state properties2. Boere et al. reported the synthesis of several aryl-substituted persilylated benzamidines and the related compound /V,N,N, N",N",Ar" -hexakis(trimethylsilyl)-l,4-benezenedicarboximidamide (hereafter referred to as HBDA) 3 the present syntheses, which are generally based on the same reaction of an aryl-substituted carbonitrile with lithium bis(trimethylsilyl)amide, offer more facile routes to representative mono- and polyfunctional carboximidamides (i.e., amidines) as well as the prototypal derivative N,N,N -tris(trimethyl-silyl)formimidamide.4 As before, the crystalline diethyl ether adduct of lithium bis(trimethylsilyl)amide5 is favored over the nonsolvated amide in these syntheses the preparation of the diethyl ether adduct is also described here. 

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