Water reaction with isonitriles

When an alkyl halide is treated with silver cyanide, reaction takes place in the usual way a silver halide and an organic compound are formed. The product, however, is not an alkyl cyanide, as is the case when potassium cyanide is used, but an isomeric compound. The substances prepared from silver cyanide are called isocyanides, isonitriles, or carbylamines. The last name is given to them on account of the fact that they unite with acids and thus resemble the amines. The addition-products do not, however, resemble salts in their chemical properties. When hydrogen chloride is passed into an ethereal solution of methyl isocyanide, a compound of the formula 2CH3NC.3HCI is formed, which is decomposed when brought into contact with water. 

Efficient stirring is required. A solution of 225 g. (5.6 moles) of sodium hydroxide in 225 ml. of water can be added to the stirred mixture of the organic substrates in dichloromethane if a more efficient mechanical stirrer is used. In the original procedure, the submitters noted an induction period of about 20 minutes which was stated to vary somewhat with the stirring rate, stirring-bar size, and relative amount of phase-transfer catalyst. Three moles of base are required for the reaction one to generate the carbene and two to react with the additional two moles of hydrochloric acid lost by the amine-carbene adduct in the isonitrile formation step. If less base is used, the excess hydrochloric acid reacts with the isonitrile by a-addition, and the yield is substantially reduced. 

The mixture can be left stirring overnight since the isonitrile is stable to the reaction conditions. Alternatively, a hot water bath can be used, with very fast stirring, to heat the mixture quickly to 35°. The bath is then removed, and after 1 hour of additional stirring, the mixture is ready for the workup procedure. 

More recently Behrens and co-workers15 were able to prepare the series of monocyano nitrosyl carbonyls by reactions such as equation (1). The Mn° compounds obtained in this work are listed in Table 6. Na[Mn(CN)(CO)3(NO)] dissolves readily in polar solvents such as water, ethanol, acetone or THF, but the solutions, even in the absence of light and air, are unstable. Crystalline salts, which are air stable, were obtained by adding such a solution to an excess of the appropriate cation. The related isonitrile species were prepared by alkylation of the cyano anions with R304. ... 

In the aromatic series the direct conversion of acid amides into acid nitriles does not take place readily but the acid itself is made from the acid amide by the reverse process as indicated above, viz., by hydration to the ammonium salt of the acid, which then yields the acid. A related method, however, is used for preparing acids from anilides of formic acid. Aniline being an ammonia compound yields acid-amidelike products with aliphatic acids, e.g. acet anilide, CH3—CO—NH— CeHs (p. 556). Such a compound can not, however, lose water in the same way as the acid amide in the above reaction for the ammonia residue in an anilide contains only one hydrogen. Nevertheless anilides lose water but in a different way. In the case of the anilide of formic acid, i.e. formanilide, H—CO—NH—CeHs, the loss of water results in a compound in which the carbon and nitrogen remain linked to the benzene ring and an iso-cyanide or iso-nitrile is formed. The isonitrile is readily converted into the nitrile and the acid may then be obtained from that. 

Polymer-bound isonitrile (423), obtained from TentaGel-NH2 through treatment of the resin with formic acid and acetic anhydride, followed by dehydration of the resulting formamide with tosyl chloride and pyridine, has been employed in the preparation of N-substituted amino add ester [349]. Thus, Ugi MCR, performed in the presence of an alcohol instead of the carboxylic component, gave rise to an imino-ether spedes (426). Several Lewis acids were tested in searching for optimal reaction conditions. Boron trifluoride etherate displayed the better yields in term of desired product of the Ugi-type reaction. Amino acid methyl esters (427) were thus obtained when using methanol as the alcohol component, after deavage from the resin of the intermediate imino-ethers by an acetone/water mixture (Scheme 87). 

Cationic Tc(I)-hexakis(2-methoxy-isobutyl-isonitrile) tetrafluroroborate is labeled by reacting tetrakis(2-methoxy-isobutyl-isonitrile)-copper(I) tetrafluroroborate adduct with 99mrp pertechnetate, using the kit formulation. Heating the reaction vial in a boiling water bath further facilitates formation of Tc(I) sestamibi. 

A catalyst-free protocol has been described by Adib for the synthesis in good to excellent yields of 3-aminoimidazo[l,2-o]pyridines and 5-aminoimidazo[2,l-6] [l,3]thiazoles via three-component reactions between 2-aminopyridines or 2-ami-nothiazoles, aldehydes and isocyanides in water (Scheme 1.10) [14]. Presumably, this process involves the initial formation of an imine, which then reacts with the isonitrile in a formal [4+2] cycloaddition. 

Scheme 31.1 (a) The products obtained from the catalytic reaction of 4-phenyl-butyne (19) with 18 both in the presence and absence of water [53a]. (b) Addition of TMSN3 to isonitriles to obtain a series of substituted IH-tetrazoles [53d]. (c) 1,3-Cycloaddition reaction between diazoacetate esters (26) and electron-poor alkene (27) to obtain 4,5-dihydro-IH-pyrazole derivatives (28) [53e]... 

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