Dichlorocarbene reaction with primary amines

The dichlorocarbene complex (TPP)Fe(CCl2) is a useful synthetic intermediate forming isocyanide complexes upon reaction with primary amines (Eq. 14) [106]. 

Although the extraction of primary amines from a basic medium with chloroform is an inadvisable procedure, on account of the formation of trace amounts of the pungent isonitriles, the specific synthesis of isonitriles by the two-phase reaction of primary amines with chloroform is unreliable. However, the application of the phase-transfer technique [e.g. 1 -5] for the controlled release of dichlorocarbene facilitates the synthesis of isonitriles in relatively high yields (Table 7.12). 

Several iron porphyrin carbenes are known1110 that are obtained by the general reaction of the chloro iron(III) complex with RCX3 (X = Cl, Br) in the presence of iron powder or sodium dithionite as in equation (101). The air sensitivity of the product depends on the nature11111112 of R. Formally these complexes could be described as iron(II) species. They are diamagnetic, and can bond an additional axial ligand. The structure of the dichlorocarbene complex [Fe(TPP)(CCl2)(H20)] has been determined by X-ray methods,1113 which showed a short Fe—C distance of 1.83 A. This complex is reactive and, for instance, with primary amines a coordinated... 

Reimer-Tiemann conversion of phenoxide into ortfto-hydroxybenzaldehyde involves an electrophilic attack by dichlorocarbene (Scheme 5.72). Carbenes also react with primary amines (carbylamine reaction) to give carbylamines (isonitriles) (Scheme 5.73). 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

Reaction with chloroform under basic conditions is a common test for primary amines, both aliphatic and aromatic, since isocyanides have very strong bad odors. The reaction probably proceeds by an SnIcB mechanism with dichlorocarbene as an intermediate ... 

Compared with primary and secondary amines, tertiary amines are virtually unreac-tive towards carbenes and it has been demonstrated that they behave as phase-transfer catalysts for the generation of dichlorocarbene from chloroform. For example, tri-n-butylamine and its hydrochloride salt have the same catalytic effect as tetra-n-butylammonium chloride in the generation of dichlorocarbene and its subsequent insertion into the C=C bond of cyclohexene [20]. However, tertiary amines are generally insufficiently basic to deprotonate chloroform and the presence of sodium hydroxide is normally required. The initial reaction of the tertiary amine with chloroform, therefore, appears to be the formation of the A -ylid. This species does not partition between the two phases and cannot be responsible for the insertion reaction of the carbene in the C=C bond. Instead, it has been proposed that it acts as a lipophilic base for the deprotonation of chloroform (Scheme 7.26) to form a dichloromethylammonium ion-pair, which transfers into the organic phase where it decomposes to produce the carbene [21]. 

The reaction of dichlorocarbene with primary amides, amidines, thioamides, and aldoximes all yield the corresponding nitriles. N,N-Disubstituted ureas likewise yield the corresponding N,N-disubstituted amine nitrile. This reaction amounts to a dehydration in the case of primary amides, aldoximes, and N,N-disubstituted ureas the elements of hydrogen sulfide are lost from thioamides, and HCN from amidines. 

Also of interest in the preparation of diazoalkanes are the di-azotization of primary amines with activating substituents in the a-position, reaction of hydrazine or hydrazides with dichlorocarbene, diazo-group transfer reactions, the oxidation of hydrazones, and condensation reactions of active methylene compounds. 

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