2.4- Dimethoxy-6-methylbenzaldehyde

A solution of 8.65 g 2,5-dimethoxy-4-methylbenzaldehyde in 30 g nitromethane was treated with 1.1 g anhydrous ammonium acetate and heated for 50 min on the steam bath. Stripping off the excess nitromethane under vacuum yielded orange crystals which weighed 12.2 g. These were recrystallized from 100 mL IPA providing yellow crystals of 2,5-dimethoxy-4-methyl-6-nitrostyrene which weighed, when dry, 7.70 g. The mp was 117-118 °C, and this was increased to 118-119 °C upon recrystallization from benzene/heptane 1 2. 

EXTENSIONS AND COMMENTARY I can t remember the exact names of the companies that went with the oil additives. STP was, I believe, it s own thing, and originally stood for Scientifically Treated Petroleum. And F-310 was, I believe, a Chevron Oil product. F-320 was, of course, the product of the wild and happy chemists at the Pharmaceutical Chemistry Department at the University of California in San Francisco, playing with what they fondly called funny drugs. And when the 2,4,6-orientation became an obvious positional isomer, the Pennzoil Oil Company s additive, Z-7, was a natural to have its name volunteered to the cause. There was one additional isomer possible, with the methyl in the 2-position and the methoxyl groups at the 4- and 6-positions. This followed the more conventional aldehyde made from 3,5-dimethoxytoluene via the Vilsmeier process, with POCl3 and N-methylformanilide. This material (2,4-dimethoxy-6-methylbenzaldehyde with mp 64-65 °C from cyclohexane or from MeOH) is completely distinct from the isomer used above (2,6-dimethoxy-4-methy lbenzaldehyde with a mp of 92-93 °C from MeOH). The amphetamine from this isomer is 2,4-dimethoxy-6-methylamphetamine, and had been christened by the chemistry crowd as Z-7.1. 

SYNTHESIS In 50 mL of benzene there was dissolved 31.6 g 2,5-dimethoxy-4-methylbenzaldehyde (see recipe for 2C-D for its preparation), 20.2 mL 1-nitropropane, and 6 mL cyclohexylamine. This solution was held at reflux in a Dean Stark apparatus for 24 h, effectively removing the water of reaction. Upon cooling, there was deposited 19.6 g of 1 -(2,5-dimethoxy-4-methylphenyl)-2-nitro-1 -butene as brilliant orange crystals. The mp, after recrystallization from MeOH, was 114-115 °C and a second recrystallization increased the mp another 2 °C. Anal. 

SYNTHESIS To a solution of 25 g 2,5-dimethoxy-4-methylbenzaldehyde (see the recipe for 2C-D for the preparation) and 29.2 g malonic acid in 50 mL anhydrous pyridine, there was added 2 mL piperidine and this was heated on the steam bath for several h. The mixture was added to a solution of 125 mL concentrated HC1 in 500 mL HjO at 0 °C, and the solid product that was formed was removed by filtration, and washed with H20. Recrystallization from aqueous EtOH yielded 31 g 2,5-dimethoxy-4-methylcinnamic acid with a mp of 163-166 °C. Anal. (C 2H1404) C,H. 

SYNTHESIS To a solution of 2,6-dimethoxy-4-methylbenzaldehyde (mp 92-93 °C from the lithiation of 3,5-dimethoxytoluene followed by reaction with N-methylformanilide) in 10 mL nitroethane, there was added 0.1 g anhydrous ammonium acetate and the mixture was heated on the steam bath for 16 h. Removal of the solvent under vacuum gave a slightly oily red-orange crystalline mass which was finely ground under 1 mL of MeOH. Filtration and a sparing wash with MeOH gave, after air drying,... 

The positions of the substituents on the aromatic nucleus of mucronine-A aldehyde (85) were determined from its NMR spectrum (39). Similarly, the NMR spectrum of A-acetylmucronine-E aldehyde (86) showed signals which corresponded well with those of a model substance, namely, 2,4-dimethoxy-5-methylbenzaldehyde (87). 

C8H8CIN04 1-chloro-2,4-dimethoxy-5-nitrobenzene 119-21-1 495.45 43.447 1.2 13424 C8H802 2-hydroxy-4-methylbenzaldehyde 698-27-1 496.15 43.514 1,2... 

A mixture of 31.6 g. of 2,5-dimethoxy-4-methylbenzaldehyde, 20.2 mL. of 1-nitropropane, 6 mL. cyclohexylamine, and 50 mL. benzene is kept at reflux in a Dean Stark apparatus for 24 hours. Cooling results in tbe spontaneous crystallization of an orange product wbicb on filtration and drying weighs 14.9 g. Recrystallization from methanol yields the product 2-nitro-(2,5-dimethoxy-4-methylphenyl)-butene-l as an orange crystalline material, mp. 115°C. Source Shulgin 1976... 

Cleavage of ethers. Of many reagents tried for demethylation of 2,6-dimethoxy-4-methylbenzaldehyde, aluminum bromide proved to be the most satisfactory. A solution of the reagent in carbon disulfide was added to a stirred solution of the... 

SYNTHESIS To a solution of 54.9 g 2,5-dimethoxy-4-methylbenzaldehyde (see the recipe for 2C-D for its preparation) in 215 g glacial acetic acid there was added 19.5 g anhydrous ammonium acetate and 30.6 g nitroethane. This mixture was heated for 3 h on the steam bath, the reaction mixture was cooled in a wet ice bath, allowing the spontaneous formation of yellow crystals. As much H20 as possible was added Oust short of a persistant cloudy oily character) and after a few additional h standing, the crystalline 1-(2,5-dimethoxy-4-methylphenyl)-2-nitropropene was removed by filtration and recrystallized from boiling acetic acid. The yield, after drying to constant weight, was 28.3 g and the mp was 87-88 °C. Anal. (C12H15N04) C,H,N. 

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