Methanol alkylating agent

Addition of sodium hydroxide to a mixture of [Co"(DMG)2] and an alkylating agent in methanol-water yields up to 50% of the organocobalt product. This appears to be the most convenient method for the preparation of organocobalt(III) derivatives, provided that the maximum yield is not required 161,163). Methods involving the reaction of Co with electrophiles are, at least with DMG complexes, more convenient than the main alternative route via Co(III) and Grignard reagents. 

This chapter compares the reaction of gas-phase methylation of phenol with methanol in basic and in acid catalysis, with the aim of investigating how the transformations occurring on methanol affect the catalytic performance and the reaction mechanism. It is proposed that with the basic catalyst, Mg/Fe/0, the tme alkylating agent is formaldehyde, obtained by dehydrogenation of methanol. Formaldehyde reacts with phenol to yield salicyl alcohol, which rapidly dehydrogenates to salicyladehyde. The latter was isolated in tests made by feeding directly a formalin/phenol aqueous solution. Salicylaldehyde then transforms to o-cresol, the main product of the basic-catalyzed methylation of phenol, likely by means of an intramolecular H-transfer with formaldehyde. With an acid catalyst, H-mordenite, the main products were anisole and cresols moreover, methanol was transformed to alkylaromatics. 

Another class of DNA alkylating agents, the Mitomycins, proved to be most promising in clinical trials. Among these, mitomycin C, shown in Fig. 6.1, exhibits significant anti-tumor activity. Its mechanism of activation consists of a complex bioreductive process. The first step is the reduction to hydroquinone, followed by a loss of methanol. This reaction fa-... 

To [Co(en)2((S)-GluOBzl)]I2 (5.0 g, 7.3 X 10 3 mol) in dry trimethyl-phosphate (18 ml, 4A sieves) contained in a conical flask equipped with a drying tube was added methyl trifluoromethane sulfonate (8.0 g, 4.9 x 10 2 mol) and the mixture was stirred at room temperature for 30 min (Caution The alkylating agent is believed to be extremely toxic. Use a hood and avoid skin and vapor contact). The deep orange solution was then slowly poured into rapidly stirred dry ether (600 ml) and the precipitated semisolid recovered by decantation. The residue was dissolved in the minimum volume of dry methanol (10-20 ml), the product reprecipitated using further dry ether (400 ml), and the solid recovered as before. A further precipitation using methanol (10-20 ml) and dry ether (800 ml) produced the complex as a finely divided solid. This was recovered by filtration (porosity 4 sin-... 

When methanol is used as the alkylating agent a methoxonium ion is formed. 

Tetramethyl-/ -phenylenediamine has been obtained in low yield by the reaction of />-phenylenediamine with various alkylating agents such as methyl iodide, methanol in the presence of hydrochloric acid at 170-200°, or formaldehyde and formic acid. In addition it has been prepared by methylating / -dimethyl-aminoaniline using methanol in the presence of hydrochloric acid at 170 -200°, followed by treatment of the resulting salts with aqueous ammonia at 180 190°. In the most recent >ro-cedure, / -phenyIenediamine was alkylated with sodium chloro-... 

A large variety of agents used in cancer treatments has been examined on reversed phase. The alkylating agent melphalan was determined in acidic methanol-water (1 1) at the 50 ng/ml plasma level (J27). ACNU. a... 

Some zeolitic and non-zeolitic molecular sieve catalysts are claimed to be capable for ortho- and para-selective alkylation using olefin as alkylating agent (refs. 1,2). Zeolite catalysts are less active and selective in the methylation of aniline by methanol (refs. 3,4). Reaction is usually carried out with a large excess of methanol since a large fraction of the alcohol decomposes without participating in the alkylation. Numerous N- and C-alkylated aniline derivatives appear in the reaction product. It was found that N-alkylation requires basic sites while C-alkylation occurs mainly on acidic sites (refs. 5-7). 

The synthesis of amphopropionates is thus similar to the amphoacetates except that, rather than sodium chloride being formed as a by-product, methanol often is. If made from methyl acrylate, there is usually about 5-7% methanol in the surfactant product. If alkylation is conducted with sodium acrylate, methyl acrylate is the more efficient alkylating agent. 

You see the reason for this solvent effect when you look at lines 2 and 3 in Table 2.1. Ions are stabilized quite considerably by solvation. Heterolyses of alkylating agents, and consequently SN1 reactions, therefore, succeed only in highly solvating media. These include the polar protic solvents such as methanol, ethanol, acetic add, and aqueous acetone as well as the polar aprotic solvents acetone, acetonitrile, DMF, NMP, DMSO, and DMPU (Figure 2.16). Unfortunately, DMPU does not solvate as well as HMPA, which is a carcinogen. 

In general, alkylation of a cobalt(I)-containing complex, prepared by NaBH4 reduction of the cobalt(III) complex, can be carried out in methanol.7 However, when a powerfully electrophilic alkylating agent is used, both alkylation of the periphery of the macrocycle and reaction with the solvent methanol can prevent formation of any cobalt alkylation product. In these cases dimethylformamide can be used in place of methanol for the alkylation reaction. 

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