Methylcarbamates reaction

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. 

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. 

Organic carbamates (RNHCOO-) commonly display monodentate coordination, as exemplified in the structurally characterized tetrahedral Co(bmc)2Cl2,438 (bmc = lV-(benzimidazoyl-2-yl)-O-methylcarbamate). An unusual route to a carbamato complex involves the reaction of Co2(CO)8 in the presence of a fourfold excess of the stable radical species tmpo, which yields the blue Co40(OOCNC9H18)6 cluster, presumably via a Co(CO)2(tmpo) intermediate, with the nitroxyl radical serving as oxidant.439... 

Figure 2. Equations showing the reaction between an JN-chlorosul-fenyl-IJ-methy 1 carbamate intermediate (or corresponding I -chloro-sulfinyl-N-methylcarbamate) and different nucleophilic agents.

Initially, the allylation reaction was studied with the /V-benzyloxycarbonylamino sulfone derived from benzaldehyde and benzoyloxycarbonyl (Cbz) carbamate (Scheme 1, R1 = Ph, R = Bn). Various catalysts were screened for the allylation of benzyl phenyl(phenylsulfonyl)methylcarbamate la with allyltrimethylsilane in dichloromethane (Table 1). Among the various Bi catalysts tested, Bi(OTf)3 4H20 was shown to be the most efficient (Table 1, entry 5). BiCl3, BiBr3, Bi(OAc)3, or Bi(OCOCF3)3 did not allow the reaction to proceed and starting material was... 

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. 

N,N -Thiobiscarbamates also may be prepared by the reaction between a methylcarbamate ester and sulfur monochloride (21). 

More recently, an interesting reaction was discovered which provides the means for the synthesis of a wide variety of methylcarbamate derivatives containing the N-sulfinyl [N-S(O)] moiety (34). In attempting to prepare isopropoxy-N-methyliminoyl chloride by the reaction between Isopropyl methylcarbamate and thionyl chloride, an unexpected product, isopropyl ll-chloro-sulfinyl-N-methylcarbamate was obtained according to the equation below. The same product also was obtained when the... 

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.)...

Nondek et al. (46) reported an innovative approach to the analysis of N-methylcarbamates in river water using postcolumn reaction detection. Separation of the underivatized N-methylcarbamates was carried out on a reversed-phase column hooked directly to a bed reactor packed with Aminex A-28, a tetraalkylammonium anion-exchange resin. The packed bed catalytically base-hydrolyzed the carbamates and... 

A De Kok, M Hiemstra, CP Vreeter. Optimization of the postcolumn hydrolysis reaction on solid phases for the routine high-performance liquid chromatographic of N-methylcarbamate pesticides in food products. J Chromatogr 507 459-472, 1990. 

Benzo[6]thienyl N-methylcarbamate (tradename Mobam), and a number of other benzo[6]thienyl carbamates possessing insecticidal activity, have been prepared from the corresponding hydroxy compounds by means of standard reactions.610,6,1 Compounds 240 (X = 0,... 

Ethyl N-benzylcarbamate and its nitroso compound have been prepared by methods similar to those described for ethyl N-methylcarbamate and its nitroso compound.2 3 2-Phenylcyclo-heptanone has been prepared by the reaction of ethyl N-nitroso-N-benzylcarbamate4 with cyclohexanone,5 by the reaction of phenyldiazomethane with cyclohexanone,6 by the reaction of ethyl N-nitroso-N-methyl carbamate with 2-phenylcyclohexa-none,6 and by the rearrangement of l-phenyl-2-cyclohexylethylene oxide.7... 

Methylcarbamate insecticides have been recently labeled with DNS-C1 [145]. The procedure involves the hydrolysis of the carbamates with 0.1 M sodium carbonate to form a phenol and methylamine [166]. The two hydrolysis products are labeled with DNS-C1 and subsequently detected and determined quantitatively by TLC on silica gel layers by scanning spectrofluorimetry in situ. The reaction conditions were examined, and optimum conditions for hydrolysis and labeling were established [167]. The overall reaction scheme is shown in Fig. 4.62. The phenol derivatives of a number of N-methylcarbamates have been separated by one- and two-dimensional TLC [168], and the fluorescence behaviour and stability of the derivatives have been examined [169]. Most of the DNS derivatives fluoresce at similar wavelengths (excitation, ca. 365 nm emission, ca. 520 nm). The fluorescence spectrum of a typical DNS derivative is shown in Fig. 4.63. The method has been applied successfully to the analysis of low concentrations of carbamates in water and in soil samples with little or no clean-up being required [170,171]. Amounts as low as 1 ng of insecticide can be detected instrumentally. Visual limits of detection are ca. 5-10 ng per spot. 

Fig.4.62. Labeling of methylcarbamate insecticides by DNS-C1.1 = Hydrolysis 2 = reaction of DNS-C1 with the amine moiety 3 reaction of DNS-C1 with die phenol moiety 4 = hydrolysis of DNS-C1 to DNS-OH.

Aresta and Quaranta studied the reactivity of alkylammonium N-alkylcarbamates (RNH3)02CNHR towards a different acylating substrate, such as dimethyl carbonate (DMC) [62a, b]. Carbamate salts (RNH3)02CNHR (R = benzyl, allyl, cyclohexyl), prepared in situ from aliphatic primary amines and C02, reacted with DMC to afford N-alkyl methylcarbamates (Equation 6.6). The reaction requires mild conditions (343-363 K 0.1 MPa C02 pressure) and can be carried out in DMC used as solvent and reagent. At 363 K, carbamate esters were obtained in satisfactory yield (45-92%) with high selectivity, as side products such as ureas, N,N-dialkylcarbamate esters, and alkylated amines were formed in very small amounts. 

A general methodology for the construction of quaternary carbon atoms at the carbonyl carbon of ketones has been successfully exploited for the facile synthesis of ( )-lycoramine (299) (Scheme 30) (165). Thus, the O-allylated o-vanillin 322 was allowed to react with vinyl magnesium bromide followed by Jones oxidation, and the acid-catalyzed addition of benzyl IV-methylcarbamate to the intermediate a,(3-unsaturated ketone furnished 323. Wadsworth-Emmons olefination of 323 with the anion derived from diethyl[(benzylideneami-no)methyl]phosphonate (BAMP) provided the 2-azadiene 324. The subsequent regioselective addition of n-butyllithium to 324 delivered a metalloenamine that suffered alkylation with 2-(2-bromoethyl)-2-methyl-l,3-dioxolane to give, after acid-catalyzed hydrolysis of the imine and ketal moieties, the 8-keto aldehyde 325. Base-catalyzed cycloaldolization and dehydration of 325 then provided the 4,4-disubstituted cyclohexenone 326. The entire sequence of reactions involved in the conversion of 323 to 326 proceeded in very good overall yield and in one pot. 

Photooxidation of parathion also occurred on leaf surfaces (18), together with isomerization and other reactions. Fenitro-thion (j),O-dimethyl 0-3-methyl-4-nitrophenyl phosphorothionate) and other phosphorothionate insecticides behaved similarly (19). Some pesticides do not require external reagents for photodegradation on surfaces carbamate insecticides such as carbaryl (1-naphthyl li-methylcarbamate), aminocarb (4-dimethylamino-3-methylphenyl li-methylcarbamate), and mexacarbate (4-dimethylamino-... 

Miles and Moye [171] have shown that several classes of nitrogen containing pesticides responded to a high performance liquid chromatography post-column reaction detector that employed ultraviolet photolysis with optional reaction with o-phthalicdicarboxaldehyde-2-mercaptoethanol followed by fluorescence detection. It was applied to the determination of jV-methylcarbamates, carbamoyl oximes, carbamethoic acids, dithiocarbamates and phenyl ureas, phenyl amides and phenyl carbamates in groundwater. See also Table 4.3. 

N-Methylcarbamate insecticides have been labelled with dansyl chloride (28). The procedure involves hydrolysis with aqueous base to form a phenol and methylamine. The reagent reacts rapidly with both compounds and the newly formed fluorescent derivatives can then be applied and separated by tic (29, 30). A typical reaction scheme is shown in Figure 7. Detection limits are good ( 1 ng per spot) and dansylation of pesticides can be accomplished with extracts from water and soil samples (31J. ... 

The photo decomposition of carbofuran (2,3-dihydro-2,2-dimethyl-7-ben-zofuranyl-AT-methylcarbamate) (III) was investigated in pure water and in the presence of various samples of organic matter (soil-extracted humic and fulvic acids) [66]. Irradiation of carbofuran (1.3 x 10 5 M) in pure water at 254 nm yielded several photoproducts however, only Ilia and Illb could be firmly identified. A step reaction was proposed first, formation of Ilia by cleavage of the O - CO bond, and second, formation of Illb by photohydrolysis of the furan ring (see Scheme 3). 

A plot of log Kj against log 1/kj (Figure 5) clearly reveals an excellent linear relationship (r-0.97) indicating that these N-methoxy N-methylcarbamates may in fact act as TSA, and the corresponding N-methylcarbamates are poor substrates and part of their inhibitory potency is likely to be due to their resemblance to the TS complex in the reaction of the enzyme with its carboxy ester substrate. Additional supportive evidence is that when Wustner et al. (41) tried to prove that the ring substituents in both series of compounds interact similarly with the bovine erythrocyte AChE active site they found a disappointing correlation between Kj and Kj and a better correlation between Ki and kj respectively for N-methoxy N-methyl and N-methylcarbamates. 

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).

Amidals 1 were prepared by the reaction of secondary allylic alcohols with benzyl hydroxy-methylcarbamate in dichloromethane using 4-methylbenzenesulfonic acid as a catalyst. The cyclization proceeded by treating 1 with mercury(II) acetate (1.25-2.0 equiv) in acetonitrile at 20 °C for 12 hours, followed by addition of sodium acetate and sodium borohydride to give the corresponding oxazolidine 2 in 60-90% yield158. 

MP2 study of substituent effects of 2-substituted alkyl ethyl methylcarbamates in homogeneous, unimolecular gas phase elimination reaction ... 

Alternatively, a modification of the Hoffman degradation reaction may be used in which the reaction is carried out in methanol to give the intermediate methylcarbamate derivative which upon alkaline hydrolysis yields the desired alpha-d y substituted amine. 

Although the direct synthesis of DMC starting from urea and methanol would be very attractive, its thermodynamics is not favorable, the calculated AG° for the direct transesterification reaction being about 3kcal at 100°C. The reaction involves two steps first, urea is converted to methylcarbamate by reaction with methanol at relatively low temperatures (ca. 100°C in the presence of a catalyst or ca. 150°C without catalyst) then, the carbamate is further reacted with methanol at 180-190°C in the presence of a catalyst to produce DMC, according to the reactions (10a) and (10b). 

When weaker bases like potassium carbonate are used as catalysts, the reactions have to be carried out at high temperatures in an autoclave in order to achieve high conversion of the starting material. Table 3 shows results obtained with aromatic and aliphatic amines. Aliphatic amines, that are harder nucleophiles, give mainly the corresponding carbamates and methylcarbamates after 22 h, while aromatic amines react slower, and their softness is responsible for the formation of mono and dimethylated products. 

Both organophosphates and N-methylcarbamates are inhibitors of acetylcholinesterase (EC 3.1.1.7) (AChE), an enzyme of critical importance in synaptic nerve impulse transmission. This enzyme hydrolyzes the neurotransmitter, acetylcholine, so that its concentration near the receptor on the post-synaptic membrane is below the threshold for initiating the post-synaptic nerve impulse, except when a pre-synaptic nerve impulse has caused the release of a pulse of transmitter. The reaction mechanism of AChE is a straightforward hydrolysis mediated by water molecules and not requiring any high energy cofactor input. Synapses of insects appear to contain very much higher concentrations of AChE than mammalian synapses, on the order of 100-fold more (46. 47. ... 

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