Alkyl isocyanates trimerization reactions

Reportedly, simple alkyl isocyanates do not dimerize upon standing. They trimerize to isocyanurates under comparable reaction conditions (57). Aliphatic isocyanate dimers can, however, be synthesized via the phosgenation of A[,A[-disubstituted ureas to yield /V-(ch1orocarhony1)ch1oroformamidine iatermediates which are subsequendy converted by partial hydrolysis and base catalyzed cycUzation. This is also the method of choice for the synthesis of l-alkyl-3-aryl-l,3-diazetidiones (mixed dimers of aromatic and aUphatic isocyanates) (58). 

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. 

Triazines (60) have been prepared by reaction of KOCN with an alkyl chloride, involving trimerization of alkyl isocyanate intermediates formed in solid-liquid PTC.109... 

Due to the lability of the alkyl-oxygen bond in alkyl cyanates, the direct trimerization reaction to 2,4.6-trialkoxy-l,3,5-triazines runs into difficulties. Often side reactions, such as isomerization to isocyanates (Lewis acid catalysis)242 or alkylation reactions with nucleophilic catalysts or anions,243 are observed. Steric hindrance or strongly electron-accepting substituents enhance the stability of alkyl cyanates in these cases selective trimerization to the corresponding... 

The reaction of alkyl bromides or alkyl iodides with potassium cyanate in DMF is a very useful method to synthesize many aliphatic isocyanate trimers. The reaction of aromatic isocyanates with ethanol in the presence of A-methylmorpholine is another useful synthetic method to produce aromatic isocyanate trimers. The initially formed ethyl carbamate is an intermediate in the trimerization reaction. 

Organic Derivatives. Although numerous mono-, di-, and trisubstituted organic derivatives of cyanuric and isocyanuric acids appear in the hterature, many are not accessible via cyanuric acid. Cyanuric chloride 2,4,6-trichloro-j -triazine [108-77-0], is generally employed as the intermediate to most cyanurates. Trisubstituted isocyanurates can also be produced by trimerization of either aUphatic or aromatic isocyanates with appropriate catalysts (46) (see Isocyanates, organic). Alkylation of CA generally produces trisubstituted isocyanurates even when a deUberate attempt is made to produce mono- or disubstituted derivatives. There are exceptions, as in the production of mono-2-aminoethyl isocyanurate [18503-66-7] in nearly quantitative yield by reaction of CA and azitidine in DMF (47). 

N-Substituted amides can be prepared by direct attack of isocyanates on aromatic rings.The R group may be alkyl or aryl, but if the latter, dimers and trimers are also obtained. Isothiocyanates similarly give thioamides. The reaction has been carried out intramolecularly both with aralkyl isothiocyanates and acyl isothiocyanates.In the latter case, the product is easily hydrolyzable to a dicarboxylic acid this is a way of putting a carboxyl group on a ring ortho to one already there (34 is... 

The cyclotrimerization reaction of alkyl- and aryl isocyanates to give trisubstituted isocya-nurates (hexahydro-5-triazinetriones) is a well known reaction. Many base and acid catalysts are effective and only highly sterically hindered isocyanates fail to undergo trimerization. In all cases the symmetric trimers 17 are obtained, and only in the trimerization of methyl isocyanate using a trialkylphosphine catalyst is the unsymmetrical trimer 18 isolated as a coproduct... 

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