Isothiocyanate nitromethane

In 1950 an alternative to the Sanger procedure for identifying N-terminal amino acids was reported by Edman—reaction with phenyl-isothiocyanate to give a phenylthiocarbamide labeled peptide. When this was heated in anhydrous HC1 in nitromethane, phenylthiohy-dantoin was split off, releasing the free a-NH2 group of the amino acid in position 2 in the sequence. While initially the FDNB method was probably the more popular, the quantitative precision which could be obtained by the Edman degradation has been successfully adapted to the automatic analysis of peptides in sequenators. 

Isothiocyanate 23 (X = CO), when treated with AICI3 in nitromethane undergoes ring closure by an intramolecular electrophilic substitution between C3 of the pyrrole ring and the isothiocyanate group to afford pyrrolo[3,2-c][l]benzazepine-10(lH)-one-4(5H)-thione 24 (Scheme 2 (2005BMCL3220, 1998MI197)). 

A major advance was devised by Pehr Edman (University of Lund, Sweden) that has become the standard method for N-terminal residue analysis. The Edman degradation is based on the chemistry shown in Figure 27.12. A peptide reacts with phenyl isothiocyanate to give a phenylthiocarbamoyl (PTC) derivative, as shown in the first step. This PTC derivative is then treated with an acid in an anhydrous medium (Edman used nitromethane saturated with hydrogen chloride) to cleave the amide bond between the N-terminal amino acid and the remainder of the peptide. No other peptide bonds are cleaved in this step as amide bond hydrolysis requires water. When the PTC derivative is treated with acid in an anhydrous medium, the sulfur atom of the C=S unit acts as... 

Condensation reaction between active methyl and methylene compounds and S-alkylated thioureas provides another useful synthetic pathway to the 1,1-enediamines. Rajappa and coworkers20 reported that nitromethane condensed with S-methylated thioureas 72, prepared from the reaction of amines and methyl isothiocyanate followed by S-methylation, to form asymmetric nitro 1,1-enediamines 73 (Scheme 5). 

Nitenpyram, from Takeda Chemical Industries, is accessible by starting from l,l-bis-(methylsrdfanyl)-2-nitroethene via sequential aminolysis with methyl-amine and 2-chloro-5-(ethylaminomethyl)pyridine, in either order (a). [150, 151] Alternatively, 2-chloro-5- (ethylaminomethyl)pyridine may also be reacted with methyl isothiocyanate, to give the corresponding thiourea this then gives the active agent by S-methylation and reaction with nitromethane (b). 

Regioselective one-pot reactions of nitromethane with isothiocyanates and oxiranes provided a series of functionalized 1,4-oxathianes in good-to-exceUent yields (Scheme 86) (14SL1839).The synthesis of a single example of a 1,3,5-dioxathiane resulted from the adamantanethione with two... 

Methyl acetate Methyl alcohol Methyl ethyl ketone Methyl nitrate Methyl thiocyanate Nitromethane Phenyl isothiocyanate Phosgene Phosphorus... 

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