Methyl isocyanate formation

In many pyrimidine ring syntheses, it is possible or even desirable to isolate an intermediate ripe for ring-closure by the formation of just one bond. For example, ethyl 3-aminocrotonate (502) reacts with methyl isocyanate to give the ureido ester (503) which may be isolated and subsequently converted into 3,6-dimethyluracil (504) by the completion of one bond. However, viewed pragmatically, the whole synthesis involves the formation of two bonds and therefore is so classified. On such criteria, only two pyrimidine/quinazoline syntheses involve the formation of only one bond. 

Key steps, as shown in Scheme 4-15, involve the formation of a urethane intermediate 37 by treating epoxide 36 with methyl isocyanate in the presence of sodium hydride. Intramolecular A-nucleophilic ring opening of oxirane affords oxazolidine 38. Subsequent treatment furnishes product 34. 

The biocidal activity of the thiadiazine (12) is probably related to the production of methyl isocyanate inside the cell by hydrolysis (equation 7). Isocyanates are known to have fungicidal properties (B-69MH1502), thought to be due to their reaction with sulfhydryl groups to form dithiocarbamates. The formation of these last mentioned compounds, by ring cleavage, might also explain the activity of 2-mercaptobenzothiazole (16). 

A typical example of the reaction of isocyanates with formamidines is shown in equation (92). Alkyl isocyanates can react in a similar way, but there can be mixed products formed under certain circumstances, as in the reaction of methyl isocyanate with N,N- dialkyl-N 1-arylformamidines (166). The predicted product (167 equation 93) is formed except when AT,AT-dimethyl-N-arylformamidines are used. In the latter case a mixture of (168) and (169) is formed (equation 94). The mechanism of the formation of (169) is shown in Scheme 104 (73HCA776). 

One of the earliest reported photochemical reactions of t-1 is the formation of the -lactam 84 in 45% yield upon irradiation in neat phenyl isocyanate (137). Because isomerization of t-1 is more rapid than cycloaddition, - -t is the presumed intermediate in this reaction. Methyl isocyanate fails to react with It. ... 

N,N -dimethylcarbodiimide. It is believed that also in this case the initial fate of the C02 carbon atom is very likely the formation of methyl isocyanate which, in this case, unfortunately could not be isolated as it further reacted to give carbodiimide. 

The toxicity of methyl isocyanate comes as a surprise if its high sensitivity to hydrolysis is considered. But actually, it may reach its site of action in the human body largely undecomposed. This is due to the reversible addition of another nucleophile to this heterocumulene. The tripeptide gluthathione, which is supposed to protect the body against oxidizing agents, adds to the C=N double bond of the isocyanate by means of its thiol group whereby the thio-carbamate is formed. When the latter decomposes in a reversal to its formation reaction, it releases the intact toxic methyl isocyanate. 

The cycloaddition of isomiinchnones with acetylenic dipolarophiles followed by the extrusion of an alkyl or aryl isocyanate (RNCO) has proven to be an effective method for the synthesis of substituted furans. The Ibata group investigated the bimolecular 1,3-dipolar-cycloaddition of aryl-substituted isomiinchnones with a number of acetylenic dipolarophiles [50]. Aryl diazoimides of type 1 were heated in the presence of a catalytic amount of Cu(acac)2 and the appropriate acetylenic dipolarophile. Formation of the substituted furan was found to be temperature-dependent higher temperatures (ca. 120°C) were needed for complete conversion to the furan. It was reasoned that the extrusion of methyl isocyanate was not as facile as the loss of carbon dioxide from sydnones and miinchnones [50]. 

However, it is not certain whether the isocyanate or the carbamate is the acylating agent in such reaction. In fact, as depicted in scheme 138, it is possible that this reaction could proceed through a mechanism involving the transient formation of methyl isocyanate rather than through the normal addition (A- ) directly to the carbonyl group followed by loss of acetaldehyde. 

The structural and stereochemical factors involved in the facile acid-catalysed rearrangement of cyclopenin (18) to viridicatin (20) have been determined. This transformation also proceeds thermally (with the formation of methyl isocyanate) and in alkaline solution. A tricyclic intermediate (19) has been proposed for the thermal reaction and it has been shown that the benzodiazepine ring and an unalkylated amide are necessary for the rearrangement but that the epoxide ring of (18) is not a requirement. 

M ethy Icy clo hexano 1 ds-2-Methylcyclohexanol trans-2-Methylcyclohexanol Methylcyclopentane 1 - M ethy Icy clo p ent ene 3-Methylcyclopentene Methyldichlorosilane Methylethyl ether Methylethyl ketone Methylethyl sulfide Methyl formate Methylisobutyl ether Methylisobutyl ketone Methyl Isocyanate Methylisopropyl ether Methylisopropyl ketone Methylisopropyl sulfide Methyl mercaptan Methyl methacrylate 2-Methyloctanoic acid 2- M ethy lp ent ane Methyl pentyl ether 2- M ethy lp ro p ane 2- M ethyl- 2- p rop ano 1 2-Methyl propene Methyl propionate Methylpropyl ether Methylpropyl sulfide Methylsilane... 

Studies detailing the thermal and photochemical reactions of these compounds are rare. The l-oxa-2,4-diazine 63 is known, from H NMR, to be in equilibrium with the spiro isomer 64, with the former predominating. Heating this mixture above 40 °C results in decomposition to acetonitrile, methyl isocyanate, and benzene (Scheme 4) <1995H(40)619>. The formation of compounds such as 63 (and 64) by cycloaddition of nitrile oxides to 8-azahepta-fulvenes is discussed in Section 9.05.10. 

Hydroxyamino)benzodiazepine (90) is acylated on oxygen upon reaction with acid chlorides (acetyl or benzoyl chloride) or isocyanates (methyl isocyanate) in the cold. On heating with acetic anhydride at 100°C, there is an oxido-reductive rearrangement to give the 3-acetoxy-2-methylamino derivative (91) (Scheme 14). This is considered to proceed by isomerization of the nitronium ion formed by cleavage of the N—O bond to the 3-carbonium ion which is trapped by the nucleophile (acetate) <80AP(313)926>. A similar mechanism is used to explain the formation of the 3-(l-imidazolyl) derivative (92) on reaction of (90) with carbonyl diimidazole. 

In situ trapping of isocyanate. The mild conditions of the "dehydration reaction using o-sulfobenzoic acid anhydride provided an opportunity to look at generating isocyanates in situ followed by immediate conversion of the isocyanate into urethane materials. This method may prove to be valuable for the generation of materials based on toxic, volatile isocyanates (i.e. methyl isocyanate). An example is shown below in Scheme V(/5) which shows the formation of 1-naphthyl N-methylcaibamate (common insecticide). 

There are several ways to identify chemicals. Each chemical or compound has a chemical name and chemical formula. Examples are ozone (O3) and methyl isocyanate (CH3NCO). The Chemical Abstract Service has a system for assigning a unique CAS Registry Number in the format xxx-xx-x. For example, ozone and methyl isocyanate are 10028-15-6 and 624-83-9, respectively. 

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