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Lego
(Newbee)
06-30-03 22:22
No 443586
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O-Methylation with Phenyltrimethylammonium chlorid
(Rated as: excellent)
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Quaternary ammonium compounds seem to tend to transfer one of the groups attached to the nitrogen to an acceptor molecule. In this case phenyltrimethylammonium chloride 1 (C6H5)N+(CH3)3 Cl- transfer one of its methyl groups to an OH group, either a phenol, an alcohol or an carboxylic acid.
This reaction seems to bee related to Post 412790 (Lego: "Betaine for O-methylation of Phenols", Novel Discourse)
Phenyltrimethylammonium chloride is rated as highly toxic unlike betaine which is used as an OTC pharmaceutical, but not as cancerogenic like methyl iodide or dimethyl sulfate. The price of 1 is about 70$/500 g from a well known chem supplier.
Unfortunately only GLC yields are given. 
O-Methylation with Phenyltrimethylammonium chloride
Acta Chemica Scandinavica, 1997, 51, 343-344
Fulltext as DjVu-File (http://www.angelfire.lycos.com/scifi2/lego/journals/10.djvu)
Alkylation with phenyltrimethylammonium chloride 1
General procedure
To a mixture containing 2.57 g, 15 mmol, of phenyltrimethylammonium chloride, 1, and 1.95 g, 6 mmol, of Cs2CO3 in 20 ml of toluene were added 10 mmol of the hydroxy compound. The resulting mixture was heated at reflux for the time indicated in tables 1 and 2. The reaction mixture was then washed first with a 1 M HCl solution, then water, and dried over anhydrous magnesium sulfate. Following evaporation of the solvent under reduced pressure, the crude product was subjected to recrystallization or bulb-to-bulb distillation. The spectroscopic and chromatographic properties of the products were in all cases in full agreement with those of authentic samples.
Table 1. Alkylation of phenols and alcohols with 1
| Entry |
Substrate |
t/h |
Product |
Half-lifea |
%Yield (isolated)b |
| 1 |
4-Methoxyphenol |
28 |
1,4-Dimethoxybenzene |
30 min |
97 (50) |
| 2 |
3-tert-Butylphenol |
27 |
3-tert-Butylanisole |
6 h |
99 (92) |
| 3 |
3-Chlorophenol |
6 |
3-Chloroanisole |
10 min |
98 (85) |
| 4 |
4-Bromophenol |
11 |
4-Bromoanisole |
3 h |
97 (56) |
| 5 |
4-Fluorophenol |
24 |
4-Fluoroanisole |
2 h |
95 (60) |
| 6 |
4-Nitrophenol |
48 |
4-Nitroanisole |
23 h |
87 (88) |
| 7 |
1-Naphtol |
21 |
1-Methoxynaphtalene |
2.5 h |
98 (87) |
| 8 |
2-Naphtol |
2 |
2-Methoxynaphtalene |
10 min |
99 (89) |
| 9 |
1-Phenylethanol |
42 |
1-Methoxy-1-phenylethane |
46 |
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| 10 |
Cinnamyl alcohol |
148 |
Cinnamyl methyl ether |
24 h |
98 (66) |
| 11 |
4-tert-Butylcyclohexanol, cis + trans |
102 |
Methoxy-4-tert-butyl-cyclohexane, cis + trans |
38 h |
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a Approximate time for 50% conversion
b GLC yields
Table 2. Selectivity on alkylation with 1
| Entry |
Substrate |
t/h |
Product |
%Yielda |
| 1 |
Salicyl alcohol |
30 |
2-Methoxybenzyl alcohol |
78 |
| 2 |
3-(2-Hydroxyphenyl)-2-propenoic acid |
27 |
Methyl 3-(2-hydroxyphenyl)-2-propionate |
92 |
| 3 |
1,5-Dihydroxy-1,2,3,4-tetrahydronaphtalene |
8 |
1-Hydroxy-5-methoxy-1,2,3,4-tetrahydronaphtalene |
99 |
| 4 |
Mandelic acid |
8 |
Menthyl mandelate |
94 |
| 5 |
2-Acetamidophenol |
7 |
2-Methoxyacetanilide |
99 |
| 6 |
2-Hydroxybenzoic acid |
1 |
Methyl 2-hydroxybenzoate |
87 |
| 7 |
2-Cyclohexyl-2-hydroxacetic acid |
29 |
Methyl 2-cyclohexyl-2-hydroxyacetate |
99 |
a GLC yields
The candle that burns twice as bright burns half as long
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