Phenyl N-methylcarbamates

Substituted phenyl N-methylcarbamates (ArOCONHMe) are one of the most widely used agricultural insecticide classes which inhibit acetylcholinesterase (AChE). The steps by which they react with AChE are shown in Eq. 13, where EOH denotes the enzyme. 

Fig. 2. Two reaction pathways of phenyl N-methylcarbamates with acetylcholinesterase the boldfaced arrow indicates an electron pair migration as the driving force of the reaction14) (reproduced with permission from Academic Press, Inc.)...

Figure 5. Relationship between the bimolecular Inhibition reaction constant (kj) of substituted phenyl N-methylcarbamates and the inhibition dissociation constant (Kj) of the corresponding N-methyl N-methoxycarbamates in their reaction with house fly acetylcholinesterase, k Values were recalculated from (42) and Kj values were from (41).

Figure 4.8 Synthesis of substituted phenyl N-methylcarbamate insecticides.

KUMIAI METACRATE METHOLCARB m-METHYLPHENYL METHYLCARBAMATE 3-METHYL-PHENYL N-METHYLCARBAMATE METOLCARB MTMC S 1065 m-TOLYLESTER KYSELINY METHYI KARBAMINOVE m-TOLYL N-METHYLCARBAMATE... 

The most important representative of phenyl N-methylcarbamates containing alkoxy substituents is 2-isopropoxyphenyl N-methylcarbamate (14), known under the name propoxur. It is an insecticide with a very broad spectrum of action and... 

Starting from hydroxybenzaldehydes, several workers prepared independently phenylcarbamates the phenyl group of which contains cyclic acetal (1,3-dioxolane) and cyclic mercaptal (1,3-dithiolane) groups (Nikles et al., 1966 Nikles, 1969 Durden and Weiden, 1969 Bachmann and Legge, 1968). Of the former, 2-(l,3-dioxolan-2-yl)-phenyl N-methylcarbamate, dioxocarb (22), and of the latter, 2-(l,3-dithiolan-2-yl)-phenyl N-methylcarbamate, (23) attained practical importance. 

Also other phenyl N-methylcarbamates have been developed in which the phenyl group is substituted by a sulfur containing moiety. The most significant compounds within this group are 3,5-dimethyl-4-methylmercaptophenyl N-methylcarbamate (methiocarb, 24), 2-ethylmercaptomethylphenyl N-methylcarbamate (ethiophen-carb, 25) and 4-benzothienyl N-methylcarbamate (MCA 600, Mobam, 26). 

The development of phenyl N-methylcarbamates of relatively simple structure was preceded at the end of the 1940s by the development of those N,N-di-methylcarbamates which contain, with the exception of dimetan (29), a heterocyclic group at the site of the phenyl group. Their development is due to the research workers of the Geigy Co., primarily to Gysih. 

Transesterification has been used for carbamate formation. Methyl N-methylcarbamate added to a mixture of phenol and a small amount of titanium(IV) ethoxide in 1,2-dichlorobenzene at 180°C with removal of methanol in a stream of nitrogen over 8 hours resulted in phenyl N-methylcarbamate in 100% conversbn with 85% selectivity (ref.30). 

Ortho Substituted Phenyl N-Methylcarbamates. Table 1 shows the enzyme Inhibition data for all of the tested carbamates. With the single exception of the 2-phenyl compound, all of the carbamates were stronger Inhibitors (higher pI50) of AChE from S-straln of the leafhopper. This clearly confirms the supposition that resistance to carbamates Is due mainly to changes In enzyme Inhibition. It Is also consistent with a study by Hama and Iwata showing a correlation between the degree of resistance and both Insecticidal activity and AChE Inhibition for several carbamate Insecticides (22). 

Magee s approach to active-site binding analysis [544, 545] may be considered as a combination of the hyperstructure concept (chapter 4.6) with the mixed approach (chapter 4.3), as can e.g. be seen from eq. 202 [545] first a hyperstructure (55) was formulated for a series of / ara-substituted phenyl-N-methylcarbamates and then... 

Phenol, 4,4 -(1-n ethylethylidene) bis-, polymer with (chloromethyl) oxirane. See Epoxy, bisphenol A/epichlorohydrin Phenol, 2-(1-methylethyl)-, methylcarbamate. See 2-lsopropyl phenyl N-methylcarbamate Phenol, 4-methyl-2-(1-methylethyl)-. See Isopropyl-p-cresol... 

A. Goldblum, M. Yoshimoto, and C. Hansch, ]. Agric. Food Chem., 29,277 (1981). Quantitative Structure-Activity Relationship of Phenyl N-Methylcarbamate Inhibition of Acetylcholinesterase. 

El Atrache LL, Sabbah S, Morizur JR Identification of phenyl-N-methylcarbamates and their transformation products in Tunisian surface water by soUd-phase extraction liquid chromatography-tandem mass spectrometry. Talanta... 

Include -0- S-D-glucopyranosylgalllc acid 6-sulphate, 3-gluco-sides of dimethyl (hyd.roxymethy 1)phenyl N-methylcarbamates (insect -... 

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