Hydrolysis of C=N compounds

Hydrolysis of imines, oximes, hydrazones, or other C=N compounds... 

A procedure for alkylation of C=0 double bonds in the presence of (metal-free) organocatalysts and non-metallic nucleophiles has been reported by the Iseki group for trifluoromethylation of aldehydes and ketones [185]. On the basis of a previous study of the Olah group [186, 187] which showed the suitability of non-chiral phase-transfer catalysts for trifluoromethylation of carbonyl compounds, Iseki et al. investigated the use of N-benzylcinchonium fluoride, 182, as a chiral catalyst. The reaction has been investigated with several aldehydes and aromatic ketones. Trifluoromethyltrimethylsilane, 181, was used as nucleophile. The reaction was, typically, performed at —78 °C with a catalytic amount (10-20 mol%) of 182, followed by subsequent hydrolysis of the siloxy compound and formation of the desired alcohols of type 183 (Scheme 6.82). 

Figure 7.2 shows the overall processes involved in a phase I reaction. Normally a phase I reaction adds a functional group to a hydrocarbon chain or ring or modifies one that is already present.4 The product is a chemical species that readily undergoes conjugation with some other species naturally present in the body to form a substance that can be readily excreted. Phase I reactions are of several types, of which oxidation of C, N, S, and P is most important. Reduction may occur on reducible functionalities by addition of H or removal of O. Phase I reactions may also consist of hydrolysis processes, which require that the xenobiotic compound have a hydrolyzable group. 

Japanese chemists (96) have reported the chemical conversion of kobusine into the chloramine (95). The latter was treated with sodium methoxide in methanol to afford compound 96 in which the bridged C-14-C-20 bond was cleaved. Reduction of kobusine with sodium in n-propanol, followed by acetylation afforded compound 88. Treatment of 88 with excess phenyl chloroformate in refluxing o-dichlorobenzene gave the carbamate 89. The latter was hydrogenated over Pd-C in methanol to obtain compound 90 in 94% yield. Further hydrogenation of 90 in the presence of platinum in acidic solution gave 91. Acidic hydrolysis of 91 afforded compound 92. The carbamate 92 was converted to the benzyl derivative 93 by treating with... 

Nevertheless, certain features of terran metabolism might benefit from a biosolvent whose properties differ from water s. For example, the instability of C=N in water constrains the structure of metabolites in water. The compound HN=C=NH, an analog of 0=C=0 (carbon dioxide), immediately hydrolyzes in water to give urea (H2NCO-NH2), whose thermodynamic instability with respect to hydrolysis in water yields carbon dioxide and ammonia. Thus, water as a solvent requires that the dominant form of carbon at the +4 oxidation state be carbon dioxide. 

Hammond, P.S., Forster, J.S., Lieske, C.N., and Durst, H.D. 1989. Hydrolysis of toxic organophosphonis compounds by o-iodosobenzoic acid and its derivatives. Journal of the American Chemical Society, 111 7860-7866. 

CF3)2C NH BF3, boron tri-chloride and -bromide have been found to interact with an equimolar amount of perfluoroisopropylidenimine at —15 to +20°C to give the aminoboranes (CT 3)2CX NH-BX2 (X = Cl or Br) hydrolysis of the trichloro-compound cleaves the B—N bond with the formation of the amine (CF3)2CC1NH2, a solid which readily decomposes at room temperature to hydrogen chloride and the parent imine. The ot-bromo-analogue (20) of this new amine has been obtained by treatment of diphenyl-boron bromide with an excess of hexafluoroisopropylidenimine ... 

Hydrolysis of the labeled compound with 2 N sulfuric acid furnished 3-amino-4-methyl-2-hexanone which, on treatment with iodine in the presence of sodium hydroxide, furnished isoleucine and iodoform. The iodoform was oxidized to carbon dioxide, while treatment of isoleucine with ninhydrin furnished 2-methylbutanal, isolated as its 2,4-dinitrophenylhydrazone. Kuhn-Roth oxidation of the aldehyde gave acetic acid which was degraded by the Schmidt procedure to carbon dioxide and methylamine. The 2-methylbutanal was also degraded stepwise by the method of Strassman. Determination of the radioactivity of the various degradation products showed that 94% of the activity was equally shared between the lactam C(2) and side-chain C(10) carbonyl atoms. The remaining activity was shared between C(4) of the lactam ring and the a> carbon atom of the ec-butyl side chain. The results are consistent with derivation of tenuazonic acid from isoleucine and two molecules of acetic acid. However, the direct incorporation of isoleucine into tenuazonic acid was not investigated. 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

The other C=N systems included in Scheme 8.2 are more stable to aqueous hydrolysis than are the imines. For many of these compounds, the equilibrium constants for formation are high, even in aqueous solution. The additional stability can be attributed to the participation of the atom adjacent to the nitrogen in delocalized bonding. This resonance interaction tends to increase electron density at the sp carbon and reduces its reactivity toward nucleophiles. 

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