In this work, a simple and reliable protocol for conversion of nitrile-amide to unsubstituted amidine–amide is developed using metal amide and/or ammonia gas. 97 Although the yield was moderate, the method succeeded in a molecule with a fairly high level of functionality. The above nucleophilic addition reactions involve NC bond formation, a bond that can also be created by insertion (at least formally) of a nitrile into a metal–N bond.148–150 Stereochemical and kinetic4,8 studies have been reported, although with few examples, for the addition of amines to nitriles at PtII centers, and the latter are indicative of the involvement, similar to the addition of alcohols (see above), of cyclic 4- and 6-center transition states, with one or two amine molecules, respectively, interacting with NC.
Amidines are less useful than imidic esters and imidoyl chlorides for the preparation of hydrazonamides.
Sulfimides can lead to the related monodentate species (18) (M = PtII 145 or CuII 146), but binding through the other N atom is also possible,147 as well as N,S-chelation as shown in (19) (M = PtII 145). But still we can't compare them because nitrogens are better bases/nucleophile by virtue of their lower electronegativity. The method has been reviewed by Grigat 〈72AG(E)949〉 and typical examples are shown in Scheme 70. Fisher, in Comprehensive Coordination Chemistry II, 2003. 1,3,5-Triazinethiones are formed in good yields by the condensation of isothiocyanates and amidines. The selective reduction of cyclic imidates (63) to the aldehyde oxidation level has been demonstrated by Shono et al.96 As shown in Scheme 19, the imidate is first alkylated on nitrogen and then reduced electrolytically in DMF in the presence of methanesulfonic acid.
Table 14. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Amidines Reduced to the Corresponding Aldehydes by Sodium and Ethanol in Liquid Ammonia52. The reaction between amidines and polychloroimines (131) is a valuable route to chloro-1,3,5-triazines with a variety of alkyl or aryl substituents (equation 66) 〈66AG(E)960a〉. The second example isn’t an imine to start with, it’s an amidine. The addition of organometallic compounds to carbodiimides is a rare example of an amidine synthesis via carbon–carbon bond formation. Supplementary data (experimental procedures and full spectroscopic data for all new compounds) associated with this article can be found, in the online version. Amidines (161) and tris(trimethylsilyl) amidines (162) react with a mixture of selenium and selenium tetrachloride to give 1λ4,2,3,5-diselenadiazol-1-ylium chlorides (163), some of which are converted into other salts for characterization. The reaction of ScCl3(thf)3 or YCl3(thf)3 with the sodium or lithium adduct [RC6H4C(NSiMe3)2]M(Et2O)n yields [RC(NSiMe3)2]2MCl(thf) which may be used to prepare other derivatives (BH4, NHR) by substitution of the chloride shown below (6).136–138. Using similar reaction conditions to those already described, 4-(2-thienyl)-1,2,3,5-dithiadiazolium chloride 24 and 4-(2-furyl)-1,2,3,5-dithiazolium chloride 25 have been synthesized (Equation 7).
With secondary amides different products are possible (Scheme 16), benzanilide (33) yields the amidine whereas with acetanilide, (34) the major product is the urea <49JA3746>. Isosteric replacement of amide groups is a classic practice in medicinal chemistry. Examples of amidines (2) and derivatives that can be synthesized in this way include the following: (i) amidines from nitrile–amine coupling induced by Lewis acids, such as metal chlorides151–156 or lanthanide(III) triflates, Ln(SO3CF3)3;157 (ii) cyclic amines (3) (n = 1–3) from the reactions of nitriles with diamines, H2NCH2(CH2)nNH2 (n = 1–3), with loss of NH3, catalyzed by Ln(SO3CF3)3157 or formed (n = 1) at PtII centers;128,137 (iii) triazines (4) from reactions of nitriles with ammonia (or of nitriles with N-substituted amidines), also catalyzed by Ln(SO3CF3)3;157 (iv) Pyrimidines (5) from the reactions of acetonitrile with secondary alicyclic amines;157 (v) carboxamides (6) from the hydrolytic amidation of nitriles with primary and secondary amines, catalyzed by PtII 32 or RuII 5–7 complexes (it has not yet been established whether the reaction proceeds via hydrolysis of an amidine intermediate, (1), or amidation of RC(O)NH2 formed by initial hydrolysis of the nitrile); (vi) the aziridine-derived product liberated from (10) (n = 1, [M] = PtII centers);128 and (vii) 1,2-diaza-1,3-dienes (17) liberated from a Pt(II or IV) center.144, R.J. Pearson, in Comprehensive Heterocyclic Chemistry III, 2008. The ScH bond lengths vary from 1.87 to 2.00 Å. Accordingly, amidines (463) and (465) are converted into hydrazonamides (464) and (466) (Scheme 55) <60JA4700, 70CRV151, 85HOU(E5)1304>. 5.