Carbon-nitrogen bond hydrolysis

Lipases are the enzymes for which a number of examples of a promiscuous activity have been reported. Thus, in addition to their original activity comprising hydrolysis of lipids and, generally, catalysis of the hydrolysis or formation of carboxylic esters [107], lipases have been found to catalyze not only the carbon-nitrogen bond hydrolysis/formation (in this case, acting as proteases) but also the carbon-carbon bond-forming reactions. The first example of a lipase-catalyzed Michael addition to 2-(trifluoromethyl)propenoic acid was described as early as in 1986 [108]. Michael addition of secondary amines to acrylonitrile is up to 100-fold faster in the presence of various preparations of the hpase from Candida antariica (CAL-B) than in the absence of a biocatalyst (Scheme 5.20) [109]. 

Hydrogenolysis is analogous to hydrolysis and ammonolysis, which involve the cleavage of a bond induced by the action of water and ammonia, respectively. Chemical bonds that are broken by hydrogenolysis reactions include carbon—carbon, carbon—oxygen, carbon—sulfur, and carbon—nitrogen bonds. An example of hydrogenolysis is the hydrodealkylation of toluene to form benzene and methane ... 

Proteases, which originally catalyze the amidic carbon-nitrogen bond breaking, also catalyze ester hydrolysis. However, in this case, the catalytic mechanism is hkely very similar and consists in the preliminary attack of the active site serine on the carbonyl carbon atom [103]. 

Adhesives based on hydrolysis resistant chemistry (i.e., adhesives D and E) show a high retention of initial properties after exposure to an aggressive corrosion environment and the failure occurs cohesively within the adhesive. The cure reactions of these adhesives involve the formation of hydrolysis resistant carbon-nitrogen bonds in reactions involving the free N-H functionality of the Versamid or Genamid hardener with the oxirane functionality of the epoxy resin that is present in the adhesive formulation ... 

In a retrosynthetic sense, formal hydrolysis of the carbon-nitrogen bond of 1.21 reveals enol 1.22 which would exist as the more stable ketone tautomer 1.23. Note that in the hydrolytic disconnection step the carbon becomes attached to a hydroxy group and the nitrogen to a hydrogen atom - there is no change in the oxidation levels of carbon or nitrogen. 

Another chemical structure in pharmaceuticals is an amide group, which is formed between a carboxylic acid and an amine and is less susceptible than ester groups to hydrolysis. This is due to the lesser electrophilicity of the carbon-nitrogen bond. The amide group is hydrolyzed as ... 

Sultams like (190) undergo aminolysis with amines by nitrogen-sulfur bond cleavage (similar to hydrolysis), and suitably functionalised sultams (191) may also suffer carbon-nitrogen bond cleavage by a bimolecular (E2) elimination reaction (Scheme 79). 

The adenylosuccinate synthetase reaction poses an interesting and general problem regarding the synthesis of carbon-nitrogen bonds coupled to nucleoside triphosphate hydrolysis. The three alternative mechanisms shown in Fig. 2 have been proposed for adenylosuccinate... 

Information of the type presented briefly for various of the exopeptidases has led to attempts to formulate a mechanism of action for peptide hydrolysis. There are two conflicting opinions about the function of the metal ions. One view, advocated strongly by Smith, is that the metal forms a chelate complex with the peptide and also is bound to the protein. The protein also interacts with the substrate through ionic or van der Waals forces. When the substrate is properly complexed, a shift of electrons makes the carbon-nitrogen bond sensitive to hydroxyl ion attack. 

Hydrolysis of an amide breaks the carbon-nitrogen bond and produces a carboxylic acid and either ammonia or an amine. The reaction resembles esters hydrolysis, but there are important differences. Ester hydrolysis occurs relatively easily, but amides resist hydrolysis. Under acid conditions, 6 M HCl and refluxing for 24 hours are required. Under basic conditions, a 40% solution of sodium hydroxide is used. Under these conditions, the salt of a carboxylate anion is produced. As in saponification of esters, an acid-base reaction to form the carboxylate anion pulls the reaction to completion. 

Nitriles are susceptible to nucleophilic addition. In their hydrolysis, water adds to the carbon-nitrogen triple bond. In a series of proton-transfer steps, an anide is produced ... 

Compounds containing carbon-nitrogen double bonds can be hydrolyzed to the corresponding aldehydes or ketones. For imines (W = R or H) the hydrolysis is easy and can be carried out with water. When W = H, the imine is seldom stable enough for isolation, and hydrolysis usually occurs in situ, without isolation. The hydrolysis of Schiff bases (W = Ar) is more difficult and requires acid or basic catalysis. Oximes (W = OH), arylhydrazones (W = NHAr), and, most easily, semicarbazones (W = NHCONH2) can also be hydrolyzed. Often a reactive aldehyde (e.g., formaldehyde) is added to combine with the liberated amine. 

The hydrolysis of carbon-nitrogen double bonds involves initial addition of water and elimination of a nitrogen moiety ... 

Related to this process is the hydrolysis of isocyanates or isothiocyanates" where addition of water to the carbon-nitrogen double bond would give an N-substituted carbamic acid (3). Such compounds are unstable and break down to carbon dioxide (or COS in the case of isothiocyanates) and the amine ... 

In addition to activation of sihcon bonds by fluoride ions as discussed in Section 2.4, silicon-silicon, silicon-carbon, silicon-hydrogen, and silicon-nitrogen bonds are activated by transition metal salts and transition metal complexes. Thus, hydrolysis of silicon-carbon bonds such as in phenyltrimethylsilane 81 can be induced by... 

Mixing trichlorosilane, acetonitrile and diphenylsulphoxide, carried out at 10°C, detonated. This accident was put down to the exothermic addition reaction of the silicon-hydrogen bond on the carbon-nitrogen triple bond of nitrile. Other interpretations are possible for instance, the effect of traces of hydrogen chloride formed by the hydrolysis of chlorosilane on acetonitrile. 

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