Carbofuran derivatives

In collaboration with 5IPCAM (Italia) we studied the synthesis and activity as insecticides of two new types of Carbofuran derivatives (V) et (VI) depicted in scheme 154 (Ref. 209, 210). 

Carbamate pesticides can easily be converted to A-nitroso derivatives in the presence of sodium nitrite under acidic conditions. The A-nitroso form of carbofuran could possibly be formed in the human stomach (Nelson et al. 1981). Since carbofuran is used routinely on a variety of crops and nitrite is a common component of the human diet and present in human saliva, nitrosation of carbamates under conditions simulating those in the human stomach is possible. Lijinsky and Schmal (1978) tested nitrosocarbofuran and five other nitrosated carbamate pesticides for carcinogenicity in rats. Nitrosocarbofuran, at 16.5 mg/kg BW administered orally once weekly for 23 weeks, was the most toxic compound tested and caused the death of several animals by liver damage early in the experiment. Among survivors, nitrosocarbofuran was the most carcinogenic,... 

Cambon, C., C. Declume, and R. Derache. 1979. Effect of the insecticidal carbamate derivatives (Carbofuran, Pirimicarb and Aldicarb) on the activity of acetylcholinesterase in tissues from pregnant rats and fetuses. Toxicol. Appl. Pharmacol. 49 203-208. 

Nelson, J., E.A. MacKinnon, H.F. Mower, and L. Wong. 1981. Mutagenicity of V-nitroso derivatives of carbofuran and its toxic metabolites. Jour. Toxicol. Environ. Health 7 519-531. 

Soils treated with Carbamyl and Carbofuran have been analysed by gas chromatography following conversion of N-methyl carbamates to their pentafluorobenzyl derivatives [84],... 

Carbosulfan, CGA-73,102, and ONCOL are derivatives of carbofuran (2,3-dihydr0-2,2-dimethylbenzofuran-7-yl methylcarbamate) which have broad spectrum activity similar to that of carbofuran but are substantially less toxic to mammals. CGA-73,102 is particularly effective as a soil insecticide by both contact and systemic action (9). Thiodicarb (10) and U-56,299 (11) are highly effective lepidopterous larvicides but are less toxic to plants and mammals than me thorny 1. U-56,299, with a rat acute... 

An example of the profound effect which change in physical property may have on the toxicological properties of a methylcarbamate insecticide is made apparent from toxicological data for a series of thiocarbamate derivatives of carbofuran (Table 1) (12). 

Table I. Toxicity of Thiocarbamate Derivatives of Carbofuran to House Flies, Mosquito Larvae and Mice...

Figure 1. Relationship between the mosquito larvicidal toxicity (log LC50) of the thiocarbamate derivatives of carbofuran, propoxur and m-isopropylphenyl methylcarbamate (MIP) and logarithm of the octanol/water partition coefficient (log P).

The downward systemic movement of ONCOL (structure given earlier), a new insecticide derived from carbofuran, has been observed (19). A significant amount of radioactivity was observed in the roots of cotton and bean plants treated topically at the base of bifoliate or trifoliated leaves with [carbamate carbonylONCOL. Downward movement of the radiolabeled material may be explained by hydrolytic degradation of the ethoxycarbonyl moiety in ONCOL to the carboxylic acid derivative, the acid function serving as a downward moving carrier. 

By analogy with malathlon, derivatives of this type were expected to be metabollcally degraded to nontoxic products In mammals by carboxylesterase action but to the parent methylcarbamate In Insects by phosphatase action (8). Thus, these derivatives were expected and found to be toxic to Insects and safe to mammals. Subsequent Investigations on the comparative metabolism of the N-dlmethoxyphosphlnothloyl derivative of carbofuran In Insects and rodents provided direct support for the rationale used In the design of these derivatives (9). 

The results of a comparative metabolism study of an aryl-sulfenyl derivative of carbofuran [2,2-dimethy1-2,3-dihydro-benzofuranyl-7 -methyl-N-(2-toluenesulfenyl)carbamate] in the house fly and white mouse Indicated the selective action of this compound to be a consequence of different metabolic pathways in insects and mammals (12). The arylsulfenyl group on the carbamate moiety allows the mammal to carry out metabolic reactions leading to less toxic products which are rapidly conjugated, while the toxic parent methylcarbamate is formed in the insect. 

A number of reports describing a wide variety of N-arylsulfenyl and N-alkylsulfenyl derivatives of different types of methylcarbamate insecticides have been disclosed in the patent literature (15,16,17,18,19). Two of these reports (18,19) describe trichloromethyl- or trlfluoromethylsulfenyl derivatives of the highly toxic methylcarbamates carbofuran and aldlcarb. 

Compounds with Improved properties of selectivity may also be obtained with derivatives where R2 In the general structure (I) Is alkyl (28,29), exemplified below with carbofuran where R and Rj are alkyl, cycloalkyl or part of a ring system. 

Carbamates act similar to organophosphates by interfering with nerve system enzymes. They are derived from carbamic acid, H NCOOH, and share many of the properties of organophosphates (Figure 18.9). The carbamate known as carbaryl (commercial trade name is Sevin) was synthesized in 1956 and has been used extensively since that time. Carbaryl s advantages are that its toxicity to mammals is low and it kills a broad spectrum of insects. It is widely used in a number of household lawn and garden products. Other common carbamates include aldicarb (Temik) and carbofuran (Furadan). 

R Lauren, MP Agnew. Determination of 2,4-dinitrophenyl ether derivatives of the phenolic metabolites of carbofuran by high-performance liquid chromatography. J Chromatogr 292 439-443, 1984. 

Pesticidal organic derivatives of carbamic acid, for which the formula is shown in Figure 15.8, are known collectively as carbamates. Some carbamate insecticides such as carbaryl, carbofuran, and pirimicarb have been in use for many years others, including Dunet, are relatively recent. Carbamate pesticides have been widely used because some are more biodegradable than the formerly popular organochlorine insecticides and have lower dermal toxicides than most common organophosphate pesticides. 

Similarly, on-column methylation has been applied to carbamate pesticides containing an active N-H group. Wien and Tanaka (41) showed that N-aryl carbamates are methylated on-column with tri-methylanilinium hydroxide-methanol to give the intact N-methyl and N-aryl derivatives. On the other hand N-methyl, 0-aryl carbamates such as carbaryl or carbofuran yielded only the methyl ethers of their respective phenols. This work has now been extended to sulfur-containing carbamates such as methomyl, methio-carb, aldicarb, etc. (42-43). Here the oxime hydrolysis products of these carbamates are chromatographed as the 0-methyl oximes. 

In the course of our attempts dedicated to the search of new pesticides, we were interested in the design of proinsecticides, especially procarbamates which are less toxic to mammalians than the parent carbamates. N-Acyl-N-methyl or N-sulfenyl-N-methyl carbamates derived from Carbofuran or Aldicarbe are quite effective insecticides and are often equal to superior to their parent compound against insects. 

The most promising representatives of this class are sulfenylated derivatives of methomyl (46) and of carbofuran (15), such as larvin (58), carbosulfan (59) and CGA-73 120(60). 

The U.S.A., through the National Pesticide Survey, " which was organized by the Environmental Protection Agency (US-EPA), established a fist of compounds based on the amount used (>7000 Tons), water solubility (>30 mg/1), and hydrolysis half-life (>25 weeks). The list includes some carbamate pesticides (e.g., aldicarb, propoxur, carbaryl, carbofuran, methiocarb, methomyl, oxamyl, cycloate, butylate, propham, and swep) and various derivatives (e.g., aldicarb sulphone, aldicarb sulphoxide, and 3-hidroxycarbofiiran). In Europe, a list of priority pollutants including pesticides was established in order to protect the environment from the adverse ecological impact of these compounds. ... 

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