Methylamines isocyanates

A convenient method for the synthesis of these low boiling materials consists of the reaction of /V,/V-dimethy1iirea [96-31-1] with toluene diisocyanate to yield an aUphatic—aromatic urea (84). Alternatively, an appropriate aUphatic—aromatic urea can be prepared by the reaction of diphenylcarbamoyl chloride [83-01-2] with methylamine. Thermolysis of either of the mixed ureas produces methyl isocyanate ia high yield (3,85). 

Naphthol is mainly used in the manufacture of the insecticide carbaryl (59), l-naphthyl A/-methyicarbamate/ iJ-2j5 - (Sevin) (22), which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate is usually prepared by treating methylamine with phosgene. Methyl isocyanate is a very toxic Hquid, boiling at 38°C, and should not be stored for long periods of time (Bhopal accident, India). India has developed a process for the preparation of aryl esters of A/-alkyl carbamic acids. Thus l-naphthyl methylcarbamate is prepared by refluxing 1-naphthol with ethyl methylcarbamate and POCl in toluene (60). In 1992, carbaryl production totaled > 11.4 x 10 t(35). Rhc ne-Poulenc, at its Institute, W. Va., facihty is the only carbaryl producer in United States. 

Doubt (75ZN(B)822) has been cast on a number of claims for the formation of 2-azetin-4-ones from cycloaddition of activated isocyanates to acetylenes (70TL119). The simple 2-azetin-4-one (246) was not isolated or even detected directly at -50 °C in the photofragmentation of compound (245), but indirect evidence for its formation was the isolation of adducts (248 X = MeO, MeNH) in the presence of methanol or methylamine (75TL1335). The most convincing evidence for an isolable 2-azetin-4-one involves treatment of the... 

Isocyanates and isothiocyanates are reduced to methylamines on treatment with LiAlH4. Lithium aluminium hydride does not usually reduce azo compounds (indeed these are the products from LiAlH4 reduction of nitro compounds, 19-59), but these can be reduced to hydrazo compounds by catalytic hydrogenation or with... 

To this end, the diazoimidazole carboxamide compound 32 was transformed first by methylamine to the methyl-triazene derivative 39, which was reacted with 11 (". -phosgene to give the desired product 40 <2002JME5448>. In another approach, 32 was directly cyclized to the bicyclic product by using 1 C-labeled methyl isocyanate. This route allowed the synthesis of both the C-2-labeled 40 and the (7-methyl-labeled samples 41 <1997JLR371, 2002JME5448> (Scheme 13). 

Methyl isocyanate is a very dangerous chemical. It was responsible for the deaths of over 2,500 people, perhaps as many as 10,000 people, in the worst industrial accident ever, that of the carbamate insecticide plant in Bhopal, India on December 3, 1984. It is a very toxic chemical. This tragedy is discussed in more detail in Chapter 25. Methyl isocyanate can be made from phosgene and methylamine, which would circumvent use of the isocyanate. Phosgene is made from chlorine and carbon monoxide, but it is also very toxic and dangerous. 

Carbimazole Carbimazole, the ethyl ester of 3-methyl-2-thioimidazolin-l-carboxylic acid (25.2.7), is synthesized by a simultaneons reaction of ethylenacetal of bromoacetaldehyde with methylamine and potassium isocyanate, forming 3-methyl-2-imidazolthione (25.2.6), which is further acylated at the nitrogen atom by ethyl chloroformiate, giving the desired product (25.2.7) [17-19]. 

Betahistine (84), a vasodilator based on the readily available feedstock a-picoline, can be synthesized by a very lengthy process (75MI20904). A shorter route employing the commercially available 2-pyridylethanol has also been described (77CZ389). Reaction of (6-hydroxymethyl-2-pyridyl)methanol with methyl isocyanate, or its bis(phenylcarbonate) with methylamine (66JAP6622185), affords anginin (85), a compound used to reduce lipids and cholesterol levels in the blood. Esterification of 2-pyridylmethanol with ibuprofen... 

Similar electroreductive silylation of a series of unsaturated nitrogen compounds such as trimethylsilyl cyanide, cyanamide or isocyanide, bis(trimethylsilyl)carbodiimide and trimethylsilyl isocyanate provide precursors of bis(trimethylsilyl)methylamine, which is useful for organic synthesis (equations 90 and 91)115. This electrochemical method is a safer and more economical process compared with the chemical process using an alkali metal such as lithium. 

Isocyanates methyl ethyl phenyl etc. Phosgene + amine methylamine ethylamine aniline etc. 

Tlie two major chemical reactions tliat were occurring in Uie Bhopal plant produced carbaiyl using metliyl isocyanate (MIC) as an intermediate. Tlie first of the consecutive reactions combined methylamine and phosgene to produce MIC tmd hydrochloric acid. Then Uie MIC reacts wiUi a-naphUiol to form Uie final product, carbaryl. There is another possible route to produce carbaiyl Uiat does not make use of the MIC intermediate. Instead, phosgene is first reacted with a-naphUiol to form a-naphthol chloroformate - Uie intermediate for Uie reaction and hydrochloric acid. Tlien a-naphUiol clUoroforniate reacts wiUi nieUiylamine to form carbaryl and hydrochloric acid. Both reaction schemes (depicted below) have Uie same overall stoichiometric equation. 

Jeevaratnam, K., Sugendran, K., Vaidyanathan, C.S. (1992a). Influence of methylamine and N,N -dimethylurea, the hydrolysis products of methyl isocyanate, on its systemic toxicity. J. Appl. Toxicol. 13 15-18. 

A few other A-substituted imines have occasionally been reduced to amine derivatives. Thus, A(-nitro imines (nitrimines) are reduced by NaBH4/dioxane %tOH/AcOH to A -nitroamines (Table 16, entry 14), and nitronate salts are reduced by BH3/THF to hydroxylamines (entry 15) via oximes. Isocyanates are reduced by LiBHEts, LiAlH(OBu )3 (at low temperature), or PhsSnH to formamides, which may be hydrolyzed in acidic workup to amines,while reduction with LAH affords A/-methylamines. ... 

Isocyanates and isothiocyanates are reduced to methylamines on treatment with... 

Conversion of aUoximes to nitriles.1 The dehydration of aldoximes to nitriles can be effected by reaction with methyl isocyanate in DMF in the presence of triethylamine to give an O-(methylcarbamoyl) aldoxime. The carbamate decomposes at 110-120° to give the nitrile and carbon dioxide and methylamine. Yields of nitriles are 65-99%. 

Derivation Synthesized directly from 1-naphthol and methyl isocyanate or from naphthyl chlorofor-mate (1-naphthol and phosgene) plus methylamine. 

A non-phosgene process for the production of methyl isocyanate, starting from methylamine and diphenyl carbonate as raw materials, has been established by EniChem/Polimeri Europa, resulting in the commercialization of two production units in the USA (1988) and China (1994) [78]. 

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