preparation of 1-ethyl-2,5-dimethoxybenzene

Vitus · Psychoscientist

Using hydrazine:

J. Org. Chem. 52, 11 (1987) 2297-2299

1-Ethyl-2,5-dimethoxybenzene : To a mixture of 100 g (0.555 mol) of 2,5-dimethoxyacetophenone and 70.5 g (1.25 mol) of potassium hydroxide in 500 mL of triethylene glycol was added 80 mL of 85% hydrazine hydrate. The mixture was refluxed for 4 h with removal of water by distillation, allowing the pot temperature to reach 190°C, and then refluxed for another 1 h. The cooled reaction mixture and aqueous distillate (which contained some codistilled product) were combined, diluted with 1 L of water, and extracted with CH2Cl2 (5 X 100 mL). The combined organic fraction was dried over MgSO4, filtered, and reduced in vacuo to give an oil, which was further purified by vacuum distillation to give 73.4 g (80% yield) of a colorless oil: bp 104-105 °C (7mm)

using Clemmensen reduction:

J. Org. Chem. 25 (1960) 1245-1247

1-Ethyl-2,5-dimethoxybenzene: Mossy zinc (140 g.) was amalgamated by a standard procedure and the amalgam refluxed with 263 ml. of concd. hydrochloric acid and 175 ml. of water while 35 g. of 2,5-dimethoxyacetophenone was added over a 1-hr. period. Reflux was continued for 22 hr., during which time 97 ml. of additional concd. hydrochloric acid was added in 10-ml. increments. The oily upper layer was then separated, dried with calcium chloride and fractionated under reduced pressure. The main fraction, b.p. 65-67.5°/5 mm., consisted of 15.7 g. (49%) of a pale yellow liquid. Refractionation gave a colorless analytical sample, b.p. 68-70°/7 mm.

Lego · Thu Jul 07, 2005 12:16 am

J. Org. Chem., 1980, (3), 501-506

2,5-Dimethoxyacetophenone.
A mixture of polyphosphoric acid (159 g, technical grade) and glacial acetic acid (8.0 g, 0.125 mol) was heated to 60 °C in a 250 mL wide-mouthed Erlenmeyer flask. p-Dimethoxybenzene (13.87 g, 1.0 mol) was added in 0.5-g portions, with vigorous stirring, at a rate which would maintain the reaction temperature between 70 and 75 °C. The dark-red reaction mixture was stirred (manually) for an additional 15 min at 75 °C, poured into ice water (800 mL), and extracted with ether (3 X 500 mL). The ethereal solution was washed with saturated NaCl solution (200 mL), dried (anhydrous sodium sulfate), and concentrated in vacuo. The residue was distilled to yield 12.4, g (69%) of 2,5-dimethoxyacetophenone: bp 96 °C (0.25 torr) 155-158 °C (11 torr);

Vitus · Psychoscientist

1,4-dimethoxybenzene -> 2,5-dimethoxyacetophenone

Using acetic acid, graphite and MeSO3H; 80°C; 30 min; 95% yield
Synthesis 13 (2004) 2165 - 2168

Haven't checked it yet but it looks interesting. I wonder if p-tosic acid could substitute?

Lego · Thu Jul 07, 2005 1:50 pm

kid a · Sat Jul 16, 2005 4:42 am

I don't have access to this journal, could someone post the full article? The tables are confusing.

It appears they only attempt the reaction using just sulfuric acid, or just PPA, and obtain yields of around 10%. Then they attempt the reaction using only methanesulfonic acid or only graphite as a catalyst and obtain only trace amounts. The combination of graphite and methanesulfonic acid as a catalyst under varying conditions fills the rest of the table. Then the second table uses these two catalysts and a third catalyst, a carboxylic acid?

Which also leaves me to question, was the reaction attempted with sulfuric acid or PPA *and* graphite as a catalyst? It's hard to imagine that it was not.

And another, could pencil "lead" be substituted for graphite powder since I think that it is mostly graphite? Wink

Kid A