Methylcarbamates

Carbamate Insecticides. These are stmcturaUy optimi2ed derivatives of the unique plant alkaloid physostigmine [57-47-6] a cholinergic dmg isolated in 1864 from Phjsostigma venenosum (see Alkaloids) (17,24,35—39). The carbamates maybe considered synthetic derivatives of the synaptic neurotransmitter acetylcholine, with very low turnover numbers. The A/,A/-dimethylcarbamates of heterocycHc enols (36) and the Ai-methylcarbamates of a variety of substituted phenols (35) with a wide range of insecticidal activity were described in 1954 (35). The latter are the most widely used carbamate insecticides, and the A/-methylcatbamates of oximes have subsequentiy been found to be effective systemic insecticides. 

Other substituted phenyl A/-methylcarbamates that have been used for insect control include metalkamate [8065-36-9] a 1 4 mixture of y -(l-ethylpropyl)-phenyl A[-methylcarbamate [672-04-8] and y -(l-methylbutyl)-phenyl A/-methylcarbamate [2282-34-0], rat oral LD qS 87, 170 mg/kg, used as a soil insecticide MTMC [1129-41 -5], 3-methylphenyl N-methylcarbamate (mp 76°C), rat oral LD q 268 mg/kg, used for rice pests MPMC [2425-10-7], 3,5-dimethylphenyl A/-methylcarbamate (mp 79°C), rat oral LD q 380 mg/kg, used for rice pests TBPMC [780-11-0], 3-/ l -butylphenyl A/-methylcarbamate (mp 140°C), mouse oral LD q 470 mg/kg, for rice pests and butacarb [2655-19-8], 3,5-di-/ l -butylphenyl A/-methylcarbamate (mp 98°C), rat oral LD q >4000 mg/kg, for sheep blowfly larvae control. 

Environmental. The A/-methylcarbamates generally are biodegradable and of low soil persistence with half-Hves for carbaryl and aldicarb of 1—2 weeks and of carbofuran of 1—4 months. Certain carbamates are highly toxic to birds with oral LD qS for mallard, eg, pheasant, in mg/kg carbofuran, 0.40, 4.2 mexacarbate, 3.0, 4.5 and methomyl, 16, 15 compared to carbaryl >2000. Fish toxicity of carbamates is generally low, but these compounds are extremely toxic to bees. In cases of human poisoning, atropine is a specific antidote. 

Another large use of naphthalene is as a raw material for the manufacture of 1-naphthyl-A/-methylcarbamate [63-25-2] (carbaryl, Sevin). Cmde or semirefined coal-tar or petroleum naphthalene can be used for carbaryl manufacture. Carbaryl is used extensively as a replacement for DDT and other products that have become environmentally unacceptable (see InsectcontrolTECHNOLOGY). 

Naphthol is mainly used in the manufacture of the insecticide carbaryl (59), l-naphthyl A/-methyicarbamate/ iJ-2j5 - (Sevin) (22), which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate is usually prepared by treating methylamine with phosgene. Methyl isocyanate is a very toxic Hquid, boiling at 38°C, and should not be stored for long periods of time (Bhopal accident, India). India has developed a process for the preparation of aryl esters of A/-alkyl carbamic acids. Thus l-naphthyl methylcarbamate is prepared by refluxing 1-naphthol with ethyl methylcarbamate and POCl in toluene (60). In 1992, carbaryl production totaled > 11.4 x 10 t(35). Rhc ne-Poulenc, at its Institute, W. Va., facihty is the only carbaryl producer in United States. 

Up until 1986 the major use for 2-j -butylphenol was in the production of the herbicide, 2-j -butyl-4,6-dinitrophenol [88-85-7] which was used as a pre- and postemergent herbicide and as a defoHant for potatoes (30). The EPA banned its use in October 1986 based on a European study which showed that workers who came in contact with 2-j -butyl-4,6-dinitrophenol experienced an abnormally high rate of reproduction problems. Erance and the Netherlands followed with a ban in 1991. A significant volume of 2-j -butyl-4,6-dinitrophenol is used worldwide as a polymerization inhibitor in the production of styrene where it is added to the reboiler of the styrene distillation tower to prevent the formation of polystyrene (31). OSBP is used in the Par East as the carbamate derivative, 2-j -butylphenyl-Ai-methylcarbamate [3766-81-2] (BPMC) (32). BPMC is an insecticide used against leaf hoppers which affect the rice fields. 

The simpler substance apoharmine according to Flury causes increased reflex excitability in the dog. In the frog it produces a like effect which with larger doses goes on to tetanus. Esterification of harmol with methylcarbamic acid induces affinities with the physostigmine type of drug. ... 

Physostigmine can be regarded as the methylcarbamate of a -amino-phenol, with an alkyl chain substituent in the o-position, relative to the amino-group. Stevens and Beutel, with this in mind, have prepared substances of the type p-RjRjjN, CO, O. CgHjR. NMCjX, where R is an alkyl radical, c.gi, isopropyl, in either the o or m-positioQ relative to the... 

Chemical Name Bis(Methylcarbamic acidl -2,6-pyridinediyldimethylene diester Common Name Pyricarbate... 

A 15.7 g (0.1 mol) of 2,6-dihydroxy methylpy rid in e hydrochloride are suspended in 176 ml of acetonitrile, and 20fi ml (0.15 mol) of triethylamine are added to the suspension. Thereafter 13 ml (0.22 mol) of methyl isocyanate are added dropwise to the reaction mixture at 20°C to 25°C. The reaction mixture is stirred at 20°C to 30°C for one hour, thereafter boiled for 3 hours, and finally the solvent is evaporated under reduced pressure. 35 to 40 g of a greyish, crystalline residue are obtained, which Is a mixture of 2,6-dihydroxymethylpyridine-bis-(N-methylcarbamate) and triethylamine hydrochloride. The obtained residue is dissolved in 80 ml of hot water, decolorized with 2 g of activated carbon when hot, and filtered after 30 minutes of stirring. The filtrate is cooled, the resulting crystal suspension is stirred at 0°C to 5°C for 3 hours, the solids are filtered off, and dried at 50°C to 60°C. 

Bj 23.3 g of 2,6-dihydroxymethylpyrldine-bis(N-methylcarbamate), prepared as described above, are dissolved in a boiling mixture of 46.6 ml of methanol and 46.6 ml of water. When the dissolution is complete, the solution is allowed to cool under slow stirring, without applying any external cooling means. The crystals start to separate at 48°C to 50°C. When the temperature of the mixture falls spontaneously below 35°C, it is cooled externally to 0°C to 5°C, and allowed to stand at this temperature for about 8 hours. Theseparated substance isfiltered off and dried at 50°C to 100°C. 22.65 g of 2,6-dihydroxymethylpyridine-bis(N-methylcarba-mate) are obtained. The quality of the product meets pharmaceutical requirements. 

The yield of this crystallization procedure is 95.7%. The above process provides the7j modification of 2,6-dihydroxymethylpyrldine-bis(N-methylcarbamate), which can be tabletted directly. The substance melts at 134°C to 1 36°C,its purity is99S% (determined by UV spectrophotometry). 

---