Methyl isocyanate methylamines

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. 

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. 

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... 

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. 

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]. 

ISOCYANATE de METHYLE (French) (624-83-9) see methyl isocyanate. ISOCYANATE METHANE (624-83-9) C2H3NO Highly flammable, polymerizable liquid. Forms explosive mixture with air [explosion limits in air (vol %) 5.3 to 26.0 flash point 0°F/-18°C 19°F/-7°C autoignition temp 995°F/535°C Fire Rating 3]. Decomposes slowly in cold water reacts violently with warm water or steam, forming carbon dioxide, dimethylurea, methylamine. 

For instance, methyl isocyanate can be prepared629 by treating diphenylamine with phosgene, which gives diphenylcarbamoyl chloride this can be converted by methylamine into the unsymmetrical urea derivative this 3-methyl-l,l-diphenylurea (226 g), when heated at 240-290°, affords methyl isocyanate (57 g, 100%), b.p. 38-40°, and the distillation residue consists of diphenylamine. 

Aminopropane, diazomethane, dimethylamine, 1,1-dimethylhydrazine, ethyl-amine, ethyldimethylamine, ethylene imine, ethylmercury chloride, formaldehyde, carbon disulfide, methanethiol, methylamine, methyl isocyanate, oxalic acid dinitrile, phosgene. 

Meroxapol 174 Meroxapol 251 Meroxapol 252 Meroxapol 254 Meroxapol 258 Meroxapol 311 Methanesulfonyl chloride Methoxymethyl isocyanate p-Methoxyphenylacetic acid Methyl acetate Methyl acetoacetate 4 -Methyl acetophenone Methylamine Methylamine, aqueous solutions Methyl anthranilate Methyl carbamate Methyl chloride 1,2-Methylenedioxybenzene N-Methylethanolamine N-Methylformamide Methyl 2-furoate 4-Methylpentanoic acid 1-Methylpiperidine 2-Methylpiperidine 3-Methylpiperidine 4-Methylpiperidine 1-Methyl-2-piperidineethanol Methyl pivalate 4-(Methylsulfonyl) acetophenone 4-(Methylthio) acetophenone... 

SCHEME 10.1 Methyl isocyanate (MIC) and its synthesis from methylamine (hottom left) and phosgene (hottom middle) (the two arrows indicate a synthesis involving multiple steps). MIC is shown also using a hall-and-stick model. 

The main derivative of 1-naphthol is carbaryl, which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate, a toxic liquid boiling at 38 °C, is obtained, among other methods, by the reaction of phosgene with methylamine. Because of its toxicity, it should only be stored for short periods to avoid possible risks during storage (Bhopal accident). 

The well-known example of the use of this synthetic pathway is Union Carbide s development of a process to manufacture methyl isocyanate by reacting methylamine with phosgene. The reaction occurs as follows ... 

The urea and carbamate derivatives can often be produced by alternative routes avoiding the manufacture and handling of isocyanates. The Du Pont process of methylamine carboxylation with carbon monoxide to give N-methylformamide, followed by oxidation to methyl isocyanate and further in situ conversion of the isocyanate to the less volatile derivatives, is only one example of a safer route to pesticides. 

In method 2, the reaction of methylamine with phosgene furnished methyl isocyanate which when reacted with 1-naphthol afforded Sevin. 

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]. 

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

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