Methylamines carbamate

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. 

The increased use of IV-methyl carbamate insecticides in agriculture demands the development of selective and sensitive analytical procedures to determine trace level residues of these compounds in crops and other food products. HPLC is the technique most widely used to circumvent heat sensitivity of these pesticides. However, HPLC with UV detection lacks the selectivity and sensitivity needed for their analysis. In the late 1970s and early 1980s, HPLC using post-column hydrolysis and derivatization was developed and refined with fluorescence detection to overcome these problems. The technique relies on the post-column hydrolysis of the carbamate moiety to methylamine with subsequent derivatization to a fluorescent isoindole product. This technique is currently the most widely used HPLC method for the determination of carbamates in water" and in fruits and vegetables." " ... 

Oxime carbamates have high polarity and solubility in water and are relatively chemically and thermally unstable. They are relatively stable in weakly acidic to neutral media (pH 4-6) but unstable in strongly acidic and basic media. Rapid hydrolysis occurs in strongly basic aqueous solutions (pH > 9) to form the parent oxime/alcohol and methylamine, which is enhanced at elevated temperature. Additionally, oxime carbamates are, generally, stable in most organic solvents and readily soluble in acetone, methanol, acetonitrile, and ethyl acetate, with the exception of aliphatic hydrocarbons. Furthermore, most oxime carbamates contain an active -alkyl (methyl) moiety that can be easily oxidized to form the corresponding sulfoxide or sulfone metabolites. 

Methyl isocyanate is a very dangerous chemical. It was responsible for the deaths of over 2,500 people, perhaps as many as 10,000 people, in the worst industrial accident ever, that of the carbamate insecticide plant in Bhopal, India on December 3, 1984. It is a very toxic chemical. This tragedy is discussed in more detail in Chapter 25. Methyl isocyanate can be made from phosgene and methylamine, which would circumvent use of the isocyanate. Phosgene is made from chlorine and carbon monoxide, but it is also very toxic and dangerous. 

The pesticides methyl and ethyl parathion were determined in run-off water er preconcentration on XAD-2. This allowed analyses of these compounds at the parts per billion level (497). Parathion and paraoxon obtained from leaf extracts and orchard soil have also been determined (492). The separation of 30 carbamate pesticides by RPC has been described (493). Various modes of postcolumn fluorometric detection of carbamate insecticides have been reported including post-colun)n reaction between o-phthalaldehyde and methylamine, a carbamate hydrolysis... 

A device can be inserted between the column and detector to automate the reaction, or reactions, of a fluorescent reagent with the eluted analyte to render it fluorescent. This principle is used to measure trace carbamates (pesticides) in the environment. The compound is reacted with sodium hydroxide then o-phthalalde-hyde, which transforms the methylamine group into a fluorescent derivative (Fig. 3.16). 

An alternative method for cleaving carbamates is exhaustive reduction with LiAlFLt to yield methylamines (Entry 3, Table 3.22). Entry 9 in Table 3.22 is an example of the nucleophilic cleavage of a carbamate with sodium methoxide. The mild reaction conditions required in the case are attributable to the structure of the amine (a vinylogous amide) these conditions are unlikely to lead to the cleavage of simple A-alkyl- or A, A-dialkylcarbamates, although A-arylcarbamates are also susceptible to nucleophilic cleavage (Entry 6, Table 3.26). 

The triethylamine salt of 2,2-dimethyl-3-(3,4-methylenedioxyphenyl)-propionic acid (5.4 g amine, 11.4 g acid) was dissolved in 10 mL 11,0 and diluted with sufficient acetone to maintain a clear solution at ice-bath temperature. A solution of 6.4 g ethyl chloroformate in 40 mL acetone was added to the 0 °C solution over the course of 30 min, followed by the addition of a solution of 4.1 g sodium azide in 30 mL H20. Stirring was continued for 45 min while the reaction returned to room temperature. The aqueous phase was extracted with 100 mL toluene which was washed once with H20 and then dried with anhy drou s Mg S04. Thi s org ani c sol uti on of the azide was heated on a steam bath until nitrogen evolution had ceased, which required about 30 min. The solvent was removed under vacuum and the residue was dissolved in 30 mL benzyl alcohol. This solution was heated on the steam bath overnight. Removal of the excess benzyl alcohol under vacuum left a residue 13.5 g of l-(N-(benzyloxycarbonyl)amino)-1,1 -dimethyl-2-(3,4-methylenedioxyphenyl)ethane as an amber oil. The dimethyl group showed, in the NMR, a sharp singlet at 1.30 ppm in CDCH,. Anal. (C19H2lN04) C,H. This carbamate was reduced to the primary amine (below) or to the methylamine (see under MDMP). 

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. 

Adducts with methylamine and dimethylamine have also been prepared 47>48>. All of the adducts are stable, crystalline solids which were shown to have the carbamate structure from a variety of observations. Trimethylamine does not react with BH3CO to give a carbamate analog an unstable 1 1 adduct is obtained. 

Conversion of aUoximes to nitriles.1 The dehydration of aldoximes to nitriles can be effected by reaction with methyl isocyanate in DMF in the presence of triethylamine to give an O-(methylcarbamoyl) aldoxime. The carbamate decomposes at 110-120° to give the nitrile and carbon dioxide and methylamine. Yields of nitriles are 65-99%. 

Diimide reduction of 96, obtained by the enzymatic oxidation of 95 (96% ee) [67], followed by O-acetylation afforded cyclohexene-diol 97 in 47% yield (Scheme 19). Compound 97 was converted into carbamate 98 by S 2 reaction with methylamine and subsequent urethane formation. Regioselective protection of the diol in 98 with TBSC1 afforded 99, which was coupled with bromoisovanillin 54 under the conditions of Mitsunobu to provide 100 (see Sect. 2.2.2). The intramolecular Heck reaction of 100 constructed the benzofuran ring including a quaternary center to afford 101 in 82% yield. Wittig reaction of 101 with Ph3P=CHBr generated vinyl bromide 102 in 49% yield as a mixture of E- and Z-isomers (E Z = ca. 1 2). 

A vast number of A-cyclopropyl amide and carbamate derivatives have been converted to the corresponding cyclopropylamines, often in excellent yield. This topic will not be covered extensively here, but the various conditions employed to bring about the reactions are listed below. Amides afford amines when treated with a strong mineral acid, usually hydrochloric acid, or a base such as methylamine followed by potassium hydroxide. Carba-... 

Starting from carbamates of type 5, N-methylamines (16) could also be prepared by reduction with LiAlH4 according to Scheme 7. Although the yield varied from moderate to high, the compounds were obtained in high purity [26]. 

By following this principle, traces of carbamates (pesticides) in the environment can be measured by saponification with sodium hydroxide and then reaction with o-phthalic aldehyde to transform the methylamine into a fluorescing derivative (Figure 3.21). 

The reasons for derivatizing carbamates, apart from their thermolability during the gas chromatographic analysis, include increased detector sensitivity (particularly with electron capture detection), increased volatility, better chromatography separation, apphcability to multiresidue and confirmatory analysis, and enhanced compound stability. There are two general approaches to the analysis of Af-methylcarbamates by derivatization, namely derivatization of the intact pesticides and derivatization of a hydrolysis product (one of which will always be the volatile methylamine). The reactions typically used to obtain derivatives of both intact and hydrolysis products of A-methylcarbamates are methylation, silylation, halogenation, acylation, and esterification. 

Fluorescence detection is not nearly as widely used as UV detection since most carbamates possess no native fluorescence. However, the structure of these pesticides contains a V-methyl substituted urethane with variations in the ester moiety. The common methylamine functionality allows the detection of compounds via a two-stage postcolumn reaction. Carbamates in the column effluent are first hydrolyzed with NaOH at a high temperature to form methylamine, which is converted into a fluorophore compound by addition of 6>-phthaldehyde (OPA) and... 

Carbaryl or sevin [63-25-2], the first carbamate in use as a pesticide was introduced in 1956. This compound is a contact insecticide used as a spraying powder against mites in winegrowing and in a variety of crops. Also, in combination with lindane [58-89-9] it is used to control potato bugs. Carbaryl is produced from 1-naphthol by reaction with methylisocyanate or by treating 1- naphthol with phosgene followed by methylamine. It is the most heavily used pesticide among all carbamates. 

C,H. This carbamate was reduced to the primary amine (below) or to the methylamine (see under MDMP). 

N-(benzyloxycarbonyl)amino)-1,1-dimethyl-2-(3,4-methylenedioxyphenyl)ethane as an amber oil. The dimethyl group showed, in the NMR, a sharp singlet at 1.30 ppm in CDCH3. Anal. (C19H21N04) C,H. This carbamate was reduced to the primary amine (below) or to the methylamine (see under MDMP). 

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