Isocyanates, reaction with halides

There are other amine surrogates that can be used to prepare amino acids by reaction with halides or other electrophilic species. Most are rather specific, but one shows some generality. Effenberger showed that reaction of methyl 5-bromohexan-oate 1.19) with potassium isocyanate gave 1.81. In this case, the isocyanate is the amine surrogate, and hydrolysis with concentrated HCl at 100°C gave 6-amino-hexanoic acid, 1.82, as its HCl salt. 4-Aminobutanoic acid, 3-aminopropanoic acid and 5-aminopentanoic acid were prepared in an identical manner.47... 

The cyclized analog of meralluride is prepared by a similar synthesis. Thus, condensation of camphoric acid (42) (obtained by oxidation of camphor) with ammonia gives the bicyclic succinimide (44). Reaction with allyl isocyanate followed by ring opening and then reaction with mercuric acetate affords the mercury derivative (45) as the acetate rather than the hydroxide as above. Reaction with sodium chloride converts that acetate to the halide (46). Displacement on mercury with the disodium salt of thioglycollic acid affords the diuretic mercaptomerine (47). ... 

Monocarbamoylation of diols is generally accomplished only with great difficulty. Reaction of the diol with an alkyl isocyanate is a possibility, but trimerization of the isocyanate frequently occurs [73]. The monocarbamic esters, which have PAF receptor antagonist activity, can be obtained however in acceptable yields via the phase-transfer catalysed in situ formation of the alkyl isocyanate from potassium isocyanate and an alkyl halide, and its subsequent reaction with the diol (see Scheme 3.8 for typical examples) [74], The diols tend to react more rapidly than do simple alcohols and m-diols are more effectively esterified that are /ra/rs-diols. Additionally, the longer the chain length between the hydroxyl centres, the less effective is the reaction. This has led to the reasonable hypothesis that a cyclic H-bonded intermediate between the two hydroxyl groups and the alkyl isocyanate are critical for the preferential and rapid formation of the carbamate. 

A number of nitrogen- and sulfur-containing heterocyclic compounds are effective corrosion inhibitors (62MI11502), the imidazolines and the benzotriazoles being particularly important types. The imidazolines are derived from ethyleneamines by reaction with fatty acids the free bases (53), the fatty acid salts (54), and various derivatives obtained by reaction with anhydrides, isocyanates or alkyl halides (55) are effective inhibitors. 

The oxidation of phenylhydrazine and 1,2-disubstituted hydrazines to hydrazones and diazenes by CI2C proceeds via formation of unstable azomethine imines.95 The conversion of alcohols into alkyl halides is achieved by reaction with CCI4 (or CBr4) in DMF under electrochemical reduction.96 The reaction of dihalocarbene X2C with DMF to form a Vilsmaier reagent (93) is proposed as the key process. The reaction of simple isocyanates (RNCO) with dimethoxycarbene normally gives hydantoin-type products. In the reaction with vinyhsocyanates such as (94), however, hydroindoles (95) are formed in good yields.97... 

There are several types of chiral derivatizing reagents commonly used depending on the functional group involved. For amines, the formation of an amide from reaction with an acyl halide [147,148], chloroformate reaction to form a carbamate [149], and reaction with isocyanate to form the corresponding urea are common reactions [150]. Carboxyl groups can be effectively esterified with chiral alcohols [151-153]. Isocynates have been used as reagents for enantiomer separation of amino acids, iV-methylamino acids, and 3-hydroxy acids [154]. In addition to the above-mentioned reactions, many others have been used in the formation of derivatives for use on a variety of packed and capillary columns. For a more comprehensive list, refer to References 155-159. 

Finally, alkyl halides are readily converted into isocyanates, in very good yields, by reaction with the silver salt of nitrocyanamide (equation 52)404. This is the first reported reaction for the preparation of isocyanates, from alkyl halides, that is of a general nature. The direct reaction of halides with metal cyanates gives very erratic results. 

The availability of amino-substituted furazans, both by direct synthesis from aminogly-oximes and via Hofmann degradation of the corresponding carboxamides, allows urea, thiourea, imino and acylamido derivatives, for example, to be prepared by reaction with isocyanates, isothiocyanates, aldehydes and acyl halides, respectively (73JPR791, 77JCS(P1)1616). Alkoxy and acyloxy derivatives are likewise formed from hydroxyfurazans (79JHC689). 

Electrophiles such as acyl halides or organic isocyanates react to give the 1-hydroxy-4-carboxylates or -carbamates, or 1,4-bis-carboxylates or -carbamates, depending on the ratio of reagents. Reactions with biselectrophiles such as bis(acyl halides) or bis-isocyanates give cyclic tetracarboxylates or tetracarbamates built up from two dioxastannolane units and two of the biselectrophile (equation 14-44). This may be a consequence of the (principally) dimeric structure of the dioxastannolanes in solution.59-87-88... 

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