Synthesis and biological activity of .alpha.-mercaptol O-(carbamoyl)oximes

Abstract

The selective condensation of a-dicarbonyl comlane-2-carboxaldehyde 0-(methylcarbamoy1)oxime pounds with one equivalent of a dithiol followed by has exhibited especially outstanding greenhouse and oxime formation and subsequent carbamoylation field control of nematodes with no phytotoxicity. has afforded a series of novel a-mercaptol 0-Structure us. activity relationships appear to be (carbamoyl)oximes, some of which possess good consistent with previously studied cholinesteraseto excellent insecticidal, acaricidal, and nematicidal inhibiting carbamates. Toxicological aspects are activity. The compound 2,4-dimethyl-1,3-dithiodiscussed.he continuing search for improved carbamate insecticides has led, in the last decade, to a class of potent T acetylcholinesterase inhibitors derived from a variety of oxime precursors. For example, significant pesticidal activity has been reported for 0-(carbamoy1)oximes of cycloaliphatic and bicyclic ketones (Kilsheimer and Manning, 1963;Weiden, 1968), 2-keto-1,3-dithiolanes (Addor, 1965), 5-keto-l,3-dithianes (Addor, 1968), alkoxy and alkylthio esters (Felton, 1968), and trisubstituted acetaldehydes (Payne et al., 1966;Weiden, 1968). Detailed structure ES. activity studies of the latter class of compounds, exemplified by 2-methyl-2-(methylthio)propionaldehyde 0-(methylcarbamoy1)-oxime (aldicarb, Temik, UC 21149), have defined certain important criteria for high or optimum acetylcholinesterase inhibition. These include a conformational similarity to acetylcholine, the presence of an a-alkylthio (or electronegative) substituent, and monomethylation of the carbamate nitrogen. The special role of sulfide sulfur is also apparent in other 0-(methylcarbamoy1)oximes ; for example, Smethyl N-[(methylcarbamoyl)oxy]thioacetimidate (methomyl, Lannate, DuPont 1179), in substituted thiophenyl carbamates (Mahfouz ef a/., 1969), and in the case of certain (methylcarbamoy1oxy)benzaldehyde mercaptals (Durden and Weiden, 1969;Nikles, 1969). The present work describes a new series of insecticidalnematicidal a-mercaptol 0-(carbamoy1)oximes of general structure I. The compound 2,4-dimethyl-1,3-dithiolane-2-carboxaldehyde 0-(methylcarbamoy1)oxime (MBR 6168, Tirpate) has demonstrated especially outstanding greenhouse and field nematode control with no phytotoxicity, and is currently under development by 3M Company. 0 0 II RIS -C I -CR3 II R,S NOCNReRs ii CH 3 < ? \OCNHCH3

Oximes of five-membered heterocyclic compounds with two heteroatoms 2. Reactions and biological activity (Review)

“…In addition, dithiolane [384] and isoxazole [385] oximes have been used as acaricides. The O-ethers of thiazole oximes exhibited biocidal activity [386].…”

Synthesis and anticholinesterasic activity of some .alpha.-thiosubstituted O-(methylcarbamoyl)oximes

“…The replacement of the weakly acidic phenol by another weakly acidic group, such as an aliphatic or alicyclic oxime, in the synthesis broadened the family of the insecticidal carbamates. Further, in order to obtain an optimized acetylcholinesterase inhibition, structure-activity studies showed that conformational similarity to acetylcholine, monomethylation of the carbamate nitrogen, and a-alkylthio substitution were essentials (Fridinger et al, 1971).…”

Photochemistry of oxime carbamates. 1. Phototransformations of aldicarb

“…An interest in the photochemical transformations of oxime carbamates, a class of effective acetylcholinesterase inhibitors (Durden and Weiden, 1974;Fridinger et al, 1971; Friedman and Gemrich, 1971;Fukuto et al, 1969;Magee and Limpel, 1977), provided the impetus for an investigation of 2-methyl-2-(methylthio)propanal 0-[(methylamino)carbonyl]oxime, aldicarb (1) (Payne et al, 1966), which is a contact poison and plant systemic insecticide for a variety of insect species.…”