Primary amide complexes

Introduction of the cobalt atom into the corrin ring is preceeded by conversion of hydrogenobyrinic acid to the diamide (34). The resultant cobalt(II) complex (35) is reduced to the cobalt(I) complex (36) prior to adenosylation to adenosylcobyrinic acid i7,i -diamide (37). Four of the six remaining carboxyhc acids are converted to primary amides (adenosylcobyric acid) (38) and the other amidated with (R)-l-amino-2-propanol to provide adenosylcobinamide (39). Completion of the nucleotide loop involves conversion to the monophosphate followed by reaction with guanosyl triphosphate to give diphosphate (40). Reaction with a-ribazole 5 -phosphate, derived biosyntheticaHy in several steps from riboflavin, and dephosphorylation completes the synthesis. 

The same activity is presented by an iridium complex [Ir(Cp )Cl2]2 that catalyses the Beckmann rearrangement of aromatic, aliphatic and heteroaromatic aldoximes 276 into the corresponding primary amide 277 in good to excellent yields (78-97%) (equation 85). 

The synthesis of aromatic primary amides through aminocarbonylation of aryl halides with ammonia is not well documented due to the technical difficulty in using gaseous ammonia. To resolve this problem, methods using ammonia equivalents such as hexamethyldisilazane (HMDS), " formamides, and a titanium-nitrogen complex have been developed. 

Figure 24-10 shows the structure of insulin, a more complex peptide hormone that regulates glucose metabolism. Insulin is composed of two separate peptide chains, the A chain, containing 21 amino acid residues, and the B chain, containing 30. The A and B chains are joined at two positions by disulfide bridges, and the A chain has an additional disulfide bond that holds six amino acid residues in a ring. The C-terminal amino acids of both chains occur as primary amides. 

The diastereomers of EBTHI zirconaaziridines are formed in comparable amounts via C-H activation, but equilibrate quickly (within an hour) to yield a thermodynamic mixture of diastereomers. Grossman observed little difference in the loss of MeH vs MeD from deuterium-labeled (EBTHI)zirconium methyl amide complexes 161 (Scheme 2). Loss of MeH and of MeD lead to different diastereomers, although their relative rate will also reflect the primary kinetic isotope effect for C-H activation. Neither kxlk2 nor k3lk4 is large, and both are largely the result of isotope effects rather than diastereoselectivity [42]. 

The carboxamide moiety was then examined, preparing several 2,4-dichlorophenoxy compounds in solution (9.37-9.43, Fig. 9.20). Replacement of the primary amide with small N-nucleophile-derived groups (9.41-9.43) maintained activity, as did the methyl ester-substituted 9.39 while the free acid 9.38, the deletion compiound 9.37, and more complex secondary amide analogues lost inhibitory activity. The hydroxamate function significantly increased the solubihty profile of 9.43 thus it was considered relevant for the optimization of the chemical series (Fig. 9.20). 

The primary amides of the group 2 elements, M(NH2)2, are nonmolecular species. " When the NH2 ligand is replaced by the bulky bis(trimethylsilyl)amido group, however, molecular complexes are formed. A complete set of structures has been obtained for Be through Ba (Table 11). The barium bis(trimethylsilyl)amides form a progression of compounds that illustrate the important relationship between ligand bulk and metal nuclearity. The base-free compound, [Ba N(SiMe3)2 ]2, exists as a dimer that can accommodate... 

Nitriles can be prepared by dehydration of primary amides (reaction 8) or of aldoximes (reaction 9), catalyzed by the Re trioxo compounds [ReOsX] (X = OSiMes, OReOs, OH) in azeotropic (e.g. toluene/water or mesitylene/water) reflux. Aqueous perrhenic acid (X = OH) is the most convenient catalyst in view of the moisture sensitivity of the others. The oxophilicity of the Re(VII) oxo-complexes is believed to play a determining role in the reactions, which are proposed to involve six-membered cyclic transition states formed upon preferential (9-coordination, relative to A-coordination, of the amide or oxime. ... 

Hydrogen and carbon monoxide were lost from the latter to form the Fe" complexes (XCIV x=0). The appearance of an absorption assigned to indicated the formation of an unstable Fe—H intermediate. Carbonyla-tion of (XCIV X = 0) gave the red cis complex (XCIV x = 2) 344). Noncoordinate irnine groups were postulated for the product (XCV R =/)-MeOC6H4) from the reaction of Fe2(CO)9 and p-methoxythio-benzamide, which contrasts with the normal reaction of iron carbonyls with primary amides and thioamides, w hich proceed to nitriles 16). 

PMR spectra cannot indicate the presence of amide hydrogen because of rapid exchange of the proton with deuterium oxide solvent. We have found that nitrogen-cobalt bonded complexes with infrared absorptions at 1575 cm. may be formed when N-bromo primary amides react with pentacyanocobaltate(II). Comparison with the spectrum of a complex formed from an N-bromo secondary amide, in which no acidic hydrogen would be present, should help resolve this problem. 

Despite its mechanistic complexity, the Hofmann rearrangement often gives high yields of both aryl- and alkylamines. For example, the appetite-suppressant drug phentermine is prepared commercially by Hofmann rearrangement of a primary amide. Commonly known by the name /cn-phen, the combination of phentermine with another appetite-suppressant, fenfluramine, is suspected of causing heart damage. 

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