Isocyanates alkyl

Urea derivadves are of general interest in medicinal chemistry. They may be obtained cither from urea itself (barbiturates, sec p. 306) or from amines and isocyanates. The latter are usually prepared from amines and phosgene under evolution of hydrogen chloride. Alkyl isocyanates are highly reactive in nucleophilic addidon reactions. Even amides, e.g. sulfonamides, are nucleophilic enough to produce urea derivatives. 

Reaction of 2-aminothiazoles with alkyl isocyanates yields 2-thiazolylureas (256) (Scheme 153) (479-483). This reaction is general and works with acyl isocyanates (484. 485). These heterocyclic ureas are also prepared by the reaction of H2O on 2-thia2olylcyanamide (486) or by action of HjOj on the corresponding thiourea (303, 481). 

Reaction of 2-imino-3-alkyl-4-thiazolines with alkyl isocyanates gives the ureas (382), which when nitrated on C-5 give the schistosomicide class of compounds (383) (Scheme 219), When nitration takes place on the ring... 

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). 

Commercially important arenesulfonyl isocyanates are not directly accessible from the corresponding sulfonamides via phosgenation due to lack of reactivity or by-product formation at elevated temperatures. A convenient method for their preparation consists of the reaction of alkyl isocyanates with sulfonamides to produce mixed ureas which, upon phosgenation, yield a mixture of alkyl and arenesulfonyl isocyanates. The desired product can be obtained by simple distillation (16). Optionally, the oxalyl chloride route has been employed for the synthesis of arenesulfonyl isocyanate (87). 

Naphthalenesulfonic acid can be converted to l-naphthalenethiol/T25 -J6 - by reduction of the related sulfonyl chloride this product has some utihty as a dye intermediate, and is converted by reaction with alkyl isocyanates to 3 -naphthyl-A/-alkylthiocarbamates, which have pesticidal and herbicidal... 

Phenyl isocyanates are generally more reactive than alkyl isocyanates in their reactions with alcohols, but with CuCl catalysis even alkyl isocyanates will react readily with primary, secondary, or tertiary alcohols (45-95% yield). ... 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

The reaction of the enamines of cyclic ketones with alkyl isocyanates, acyl isocyanates, phenyl isothiocyanates, and acyl isothiocyanates has also been reported 112). The products are the corresponding carboxamides. The products from the isothiocyanates have been utilized as intermediates in the preparation of various heterocyclic compounds 113). 

Resonance Energies of Carbon Dioxide, Alkyl Isocyanates, etc. 

The reactive compound chlorosulfonyl isocyanate (ClSOaNCO, forms P-lactams even with unactivated alkenes, as well as with imines, allenes, conjugated dienes, and cyclopropenes. With microwave irradiation, alkyl isocyanates also... 

This procedure is one used by Schroter for preparing alkyl isocyanates.1... 

Rare Earth Metal-Initiated Polymerizations of Alkyl Isocyanates. . 72... 

Cyanates contain the OCN group. Inorganic cyanates that are formed industrially by the oxidation of cyanide salts hydrolyze in water to form ammonia and bicarbonate ion. Alkyl cyanates are insoluble in water and form cyanurates. Alkyl isocyanates contain the OCN radical, are formed from cyanates, and, like cyanates, are readily hydrolyzed. Thiocyanates (SCN group) are formed from cyanides and sulfur-containing materials and are relatively stable. 

The method gives better yields, utilizes more readily available starting materials, and is much less laborious than the hydrolysis of N-methyl-N-alkylarenesulfonamides and -nitroso-N, N-di-alkylanilines, or the lithium aluminum hydride reduction of alkyl isocyanates. Compared to the closely related procedure of Lucier, Harris, and Korosec,12 in which the N-benzylidenealkyl-amine is treated with dialkyl sulfate at atmospheric pressure, the present procedure tends to give higher yields and purer products, but it is less convenient because of the need for a pressure vessel. 

Additions of lithiated alkoxyallenes to alkyl-substituted isocyanates and isothiocyanates as electrophiles were recently disclosed by Nedolya and co-workers [87-91]. A short route to N-[2(5H)-furanylidene]amines 133 consists in the addition of lithiated methoxyallene 42 to alkyl isocyanates 132 and silver acetate-mediated cydi-zation of the intermediate (Scheme 8.33) [87]. 

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. 

The anodic oxidation of substituted allenes [76-79] and hetero-allenes [80-85] has been extensively studied by Becker and coworkers. Oxidation of secondary and tertiary alkyl isothiocyanates resulted in an ot-cleavage processes [77]. Primary alkyl isocyanates yielded amides and carbonyl compounds due to the nucleophilic involvement of either acetonitrile or water [80]. Primary alkyl isothiocyanates 48 afforded five-membered thiadiazolidine 49 and 50 and... 

A theoretical study of the reaction of water and methanol with HNCO has led to a prediction of a four-centred transition state for both reactions. The interactions of water and of alcohols with alkyl isocyanates have been the subject of both experimental and theoretical study. In the case of hydration, evidence for initial interaction of water and water clusters (n = 1-3) across the N=C bond of the alkyl isocyanate... 

Trialkylsilyl radicals add to alkyl isocyanate to form imidoyl radicals 56 (Reaction 5.38). Detailed EPR studies established intermediates 56 to be strongly bent at the carbon bearing the unpaired electron [76], The absolute rate constant for the reaction of Et3Si radical with ieri-butyl isocyanate was found to be 5.5 x 10 s at 27 °C [13], whereas the relative rate of the addition of MesSi radicals to alkyl isocyanates was found to decrease in the... 

This reaction is typical for the synthesis of sulfonylureas it is mildly exothermic and proceeds smoothly in a variety of inert aprotic solvents. The product is usually obtained in very high yield, as a fine crystalline precipitate. The sulfonyl isocyanates are readily prepared from the substituted benzene sulfonamides by reaction with phosgene, Fig. 3, in the presence of an alkyl isocyanate, for example, butyl isocyanate in an inert solvent at 120 to 140°C according to the general procedure of H. Ulrich and A. A. R. Sayigh (Ref. 3). 

Aqueous solutions of methyl isothiocyanate are slowly oxidized in air to give 2,4-dimethyl-1,2,4-thiadiazoline-3,5-thione (71) <82AHC(32)285>. When mixtures of alkylisothiocyanates and alkyl-isocyanates are chlorinated, 3-oxathiadiazolium salts (198) are formed via an intermediate iminochloromethylsulfenyl chloride (199). Hydrolysis of these salts yields 2,4-dialkyl-1,2,4-thia-diazolidin-3,5-diones (200) (Scheme 45) <80USP4183816>. 

---