Amidines reduction

Neither the oxide nor the amidine function are in fact required for activity. Treatment of the oxime, 7, with chloro-acetyl chloride in the presence of sodium hydroxide proceeds directly to the benzodiazepine ring system (14)(the hydroxyl ion presumably fulfills a role analogous to methylamine in the above rearrangement). Reduction of the N-oxide function of 14 leads to diazepam (15). ... 

Complete reduction of the azepine ring to hexahydroazepine has been effected with hydrogen and palladium,40 or platinum,135 239 catalysts. For example, ethyl 1 f/-azepine-l-carboxylate is reduced quantitatively at room temperature to ethyl hexahydroazepine-l-carboxylate (92% bp 118 —120 3C).134 136 TV-Phenyl-S/Z-azepin -amine (1), however, with platinum(IV) oxide and hydrogen in methanol yields the hexahydroazepine 2 in which the amidine unit is preserved in the final product.34 The same result is obtained using 5% palladium/barium carbonate, or 2 % palladium/Raney nickel, as catalyst. 

Little progress has been made in the field of Group 15 metal amidinate and guanidinate derivatives. Only very recently some exciting results have been reported which demonstrate that this area may hold some real surprises and merits further exploration. It was found that amidinato ligands are capable to stabilize novel amidodiarsenes. Reduction of the four-membered ring As(III)... 

Oxalamidinate anions represent the most simple type of bis(amidinate) ligands in which two amidinate units are directly connected via a central C-C bond. Oxalamidinate complexes of d-transition metals have recently received increasing attention for their efficient catalytic activity in olefin polymerization reactions. Almost all the oxalamidinate ligands have been synthesized by deprotonation of the corresponding oxalic amidines [pathway (a) in Scheme 190]. More recently, it was found that carbodiimides, RN = C=NR, can be reductively coupled with metallic lithium into the oxalamidinate dianions [(RN)2C-C(NR)2] [route (c)J which are clearly useful for the preparation of dinuclear oxalamidinate complexes. The lithium complex obtained this way from N,N -di(p-tolyl)carbodiimide was crystallized from pyridine/pentane and... 

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 >. 

With RCH2CN, however, there is a tendency for Grignard reagents to remove a proton from the CH2 group, leading to more complex reactions. Reduction with Li AlH4e (c/. p. 214) yields RCH2NH2, NH3 adds to (193), in the presence of NH4 Cle to yield salts of amidines, RC(NH2)=NH2 Cle. Acid-catalysed addition of alcohols,... 

The chalcogenatriazinyl systems (87) are prepared by reduction of the corresponding S-Cl or Se-Cl derivatives (88) with triphenylantimony.235 These six-membered rings form cofacial diamagnetic dimers in the solid state. The monohalogenated derivatives 88 (E=S, Se) are best prepared by the condensation of imidoyl amidines with SC12 or SeCl4, respectively. 

Two technical applications of C = N-X substrates have been reported. Noyori s Ru-PP-NN catalyst system was successfully applied in a feasibility study by Dow Chirotech for the hydrogenation of a sulfonyl amidine [77], while Avecia showed the commercial viability of its CATHy catalyst based on a pentamethyl cyclopentadienyl Rh complex for the reduction of phosphinyl imines [78] (Fig. 34.11). 

Reduction of Amidines, Thioamides, Imidoyl Chlorides and Hydrazides 171... 

REDUCTION OF AMIDINES, THIOAMIDES, IMIDOYL CHLORIDES AND HYDRAZIDES... 

There is one report of reductive cleavage of the imidazole ring. Treatment of 122 with sodium dithionate in aqueous ammonia yielded amidine 123, which on hydrolysis with acid gave 124. Compound 124 was obtained directly on reduction with sodium dithionate in aqueous ethanolic sodium bicarbonate (83JHC1003). 

Reduced pyrimidines are much less stable toward hydrolysis than the fully conjugated analogs, and this is often used synthetically to produce amino acids and diamines. The BH3 reduction of cyclic amidines (1,4,5,6-tetrahydropyr-imidines) to hexahydropyrimidines, and their subsequent hydrolysis was mentioned above <1999JFIC105>, but there are many more examples. For instance, m-cyclobutane /5-amino acids 544 can be prepared from the cyclobutane derivatives 542 formed by the [2-F2] photocycloaddition reaction between uracil and ethylene <2002TL6177, 2004TL7095, 2006SL1394>. 

Nucleophilic substitutions at the azepine nucleus are confined mainly to derivatives of hydroazepines such as lactim ethers, imidoyl chlorides and amidines, and to hydride ion reductions of carbonyl and imine groups (see Section 5.16.3.5.2). In addition some transan-nular nucleophilic displacements have been described, but such reactions are not as common with azepines as with larger ring heterocycles. 

Hydrodebromination accompanies the partial reduction of the aminobromoazepine (111 X=Br) to its amidine hydrobromide (67JOC2367). Partial reduction of 2-dimethylamino-3H-azepine to the 4,5-dihydro derivative is possible with hydrogen and 5% Pd-C (73CC327). Wolff-Kishner reduction of 2,3,4,5-tetrahydro-2-phenyl-lfT-l-benzazepin-4-one proceeds normally to give the tetrahydroazepine (79JOC4213). 

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