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original synth with references that i left out here for brevity ^^;
Introduction:
Syringaldehyde has been prepared by the oxidation of eucalypt lignin with nitrobenzene and alkali. It has been methylated with dimethyl sulphate and mescaline has been synthesized from the 3,4,5-trimethoxybenzaldehyde so formed.
Mescaline, 3,4,5-trimethoxyphenethylamine (IV), the hallucinatory principle of "peyote", was isolated in 1896 by Heffter, and its chemistry has been studied in detail. Numerous syntheses have been developed and many of these utilized 3,4,5-trimethoxybenzoic acid or one of its derivatives as starting material. Other synthetic routes made use of 3,4,5-trimethoxybenzaldehyde (II), and Slotta and Heller and Slotta prepared their starting material, trimethoxyphenylpropionic acid, by condensation of the substituted benzaldehyde with malonic acid and reduction of the resulting cinnamic acid. Mescaline was then obtained by Hofmann degradation of the trimethoxyphenylpropionamide.
Slotta and Szyska obtained mescaline directly by condensing II with nitromethane and reducing electrolytically the ω-nitro-trimethoxystyrene (V). The latter also has been reduced with lithium aluminum hydride. Pure crystalline mescaline has also been synthesized by condensation of 3,4,5-trimethoxybenzaldehyde with potassium cyanide followed by acetylation and catalytic reduction to the amine.
Syringaldehyde, 3,5-dimethoxy-4-hydroxybenzaldehyde (I), is an attractive alternative starting material. D.E. Bland and coworkers reported its preparation by the oxidation of certain eucalypt lignins with nitrobenzene and alkali. Working on a small scale they showed that Eucalyptus regnans (Mountain Ash), E. obliqiia (Messmate Stringybark) and E. diversicolor (Karri) gave better than 5% yields of syringaldehyde. It was decided, therefore, to study the preparation of mescaline from these three species.
The first stage is the methylation of the free phenolic group of syringaldehyde which can be accomplished either with dimethyl sulphate and alkali, or with diazomethane. Only the first method was examined in detail, since diazomethane would not be favored as a large-scale reagent. Both the electrolytic and the lithium aluminum hydride reduction of V present difficulties on a large scale, especially in the decomposition of the lithium-alanate complex. On the other hand, cyanohydrin formation can be performed quite readily by the reaction of potassium cyanide with the aldehyde bisulphite compound, and catalytic reduction of III is straight-forward and cheaper. This route was therefore preferred.
Procedure:
75 g portions of air-dry sawdust from kiln-dried timber were oxidized with nitrobenzene and alkali at 150°C according to the method of Bland. The mean yield of syringaldehyde from E. regnans was 4.9%, from E. obliqua 3.1% and from E. diversicolor 3.2%. The use of a mechanical stirrer in the autoclave would probably have increased the yields, which may also depend on the particle size of the sawdust.
75 of sawdust gave the largest volume of solution which could be extracted conveniently by hand. For larger volumes, a continuous extractor was used in which hot benzene was allowed to flow through the aqueous phase, but during the long period in which the benzene extract was kept at 80°C, a large proportion of the syringaldehyde decomposed. For large-scale operation, the benzene extract would have to be kept at a lower temperature by the use of a climbing film or flash evaporator.
The crude extract which contained both syringaldehyde and vanillin was analyzed using a mass spectrometer. since spectrophotometric analyses are of little use in distinguishing these two compounds. The syringealdehyde was separated by fractional recrystallization from benzene until its mass spectrum, compared with that of a mixture of syringaldehyde and vanillin in known proportions, showed it to be at least 95% pure.
At first syringaldehyde was methylated with dimethyl sulphate for one hour at 0-50°C, giving yields of 42%. It was found that heating at 70°C for a further hour increased the yield of 3,4,5-trimethoxybenzaldehyde to 56%. Heating above these temperatures lowered the yield, probably because of a Canizzaro reaction. 3,4,5-trimethoxybenzaldehyde cyanohydrin was prepared from 3,4,5-trimethoxybenzaldehyde according to the method of Kindler and Peschke using the bisulphite compound as an intermediate. This method eliminates the use of gaseous hydrogen cyanide and is considerably safer. 3,4,5-trimethoxybenzaldehyde cyanohydrin acetate was prepared by refluxing the cyanohydrin with acetic anhydride.
It has been reported that if the cyanohydrin acetate could be reduced catalytically in glacial acetic acid using palladium black as the catalyst. However, when this system was used, no mescaline was formed. Examination of the reaction mixture with a mass spectrometer indicated that the active palladium black had removed boda acetyl and cyanide groups from the 3,4,5-trimethoxybenzaldehyde cyanohydrin acetate. The reduction was successful using a less active palladium black and absolute ethanol as solvent. Mescaline was finally isolated as the sulphate.
Based on the weight of kiln-dried wood, the overall yields were 1% for E. Tegnans and 0.7% for the other two species. As the synthetic route is comparatively simple, it would appear that eucalypt sawdust can be used for the economic production of mescaline on a large scale.
Introduction:
Syringaldehyde has been prepared by the oxidation of eucalypt lignin with nitrobenzene and alkali. It has been methylated with dimethyl sulphate and mescaline has been synthesized from the 3,4,5-trimethoxybenzaldehyde so formed.
Mescaline, 3,4,5-trimethoxyphenethylamine (IV), the hallucinatory principle of "peyote", was isolated in 1896 by Heffter, and its chemistry has been studied in detail. Numerous syntheses have been developed and many of these utilized 3,4,5-trimethoxybenzoic acid or one of its derivatives as starting material. Other synthetic routes made use of 3,4,5-trimethoxybenzaldehyde (II), and Slotta and Heller and Slotta prepared their starting material, trimethoxyphenylpropionic acid, by condensation of the substituted benzaldehyde with malonic acid and reduction of the resulting cinnamic acid. Mescaline was then obtained by Hofmann degradation of the trimethoxyphenylpropionamide.
Slotta and Szyska obtained mescaline directly by condensing II with nitromethane and reducing electrolytically the ω-nitro-trimethoxystyrene (V). The latter also has been reduced with lithium aluminum hydride. Pure crystalline mescaline has also been synthesized by condensation of 3,4,5-trimethoxybenzaldehyde with potassium cyanide followed by acetylation and catalytic reduction to the amine.
Syringaldehyde, 3,5-dimethoxy-4-hydroxybenzaldehyde (I), is an attractive alternative starting material. D.E. Bland and coworkers reported its preparation by the oxidation of certain eucalypt lignins with nitrobenzene and alkali. Working on a small scale they showed that Eucalyptus regnans (Mountain Ash), E. obliqiia (Messmate Stringybark) and E. diversicolor (Karri) gave better than 5% yields of syringaldehyde. It was decided, therefore, to study the preparation of mescaline from these three species.
The first stage is the methylation of the free phenolic group of syringaldehyde which can be accomplished either with dimethyl sulphate and alkali, or with diazomethane. Only the first method was examined in detail, since diazomethane would not be favored as a large-scale reagent. Both the electrolytic and the lithium aluminum hydride reduction of V present difficulties on a large scale, especially in the decomposition of the lithium-alanate complex. On the other hand, cyanohydrin formation can be performed quite readily by the reaction of potassium cyanide with the aldehyde bisulphite compound, and catalytic reduction of III is straight-forward and cheaper. This route was therefore preferred.
Procedure:
75 g portions of air-dry sawdust from kiln-dried timber were oxidized with nitrobenzene and alkali at 150°C according to the method of Bland. The mean yield of syringaldehyde from E. regnans was 4.9%, from E. obliqua 3.1% and from E. diversicolor 3.2%. The use of a mechanical stirrer in the autoclave would probably have increased the yields, which may also depend on the particle size of the sawdust.
75 of sawdust gave the largest volume of solution which could be extracted conveniently by hand. For larger volumes, a continuous extractor was used in which hot benzene was allowed to flow through the aqueous phase, but during the long period in which the benzene extract was kept at 80°C, a large proportion of the syringaldehyde decomposed. For large-scale operation, the benzene extract would have to be kept at a lower temperature by the use of a climbing film or flash evaporator.
The crude extract which contained both syringaldehyde and vanillin was analyzed using a mass spectrometer. since spectrophotometric analyses are of little use in distinguishing these two compounds. The syringealdehyde was separated by fractional recrystallization from benzene until its mass spectrum, compared with that of a mixture of syringaldehyde and vanillin in known proportions, showed it to be at least 95% pure.
At first syringaldehyde was methylated with dimethyl sulphate for one hour at 0-50°C, giving yields of 42%. It was found that heating at 70°C for a further hour increased the yield of 3,4,5-trimethoxybenzaldehyde to 56%. Heating above these temperatures lowered the yield, probably because of a Canizzaro reaction. 3,4,5-trimethoxybenzaldehyde cyanohydrin was prepared from 3,4,5-trimethoxybenzaldehyde according to the method of Kindler and Peschke using the bisulphite compound as an intermediate. This method eliminates the use of gaseous hydrogen cyanide and is considerably safer. 3,4,5-trimethoxybenzaldehyde cyanohydrin acetate was prepared by refluxing the cyanohydrin with acetic anhydride.
It has been reported that if the cyanohydrin acetate could be reduced catalytically in glacial acetic acid using palladium black as the catalyst. However, when this system was used, no mescaline was formed. Examination of the reaction mixture with a mass spectrometer indicated that the active palladium black had removed boda acetyl and cyanide groups from the 3,4,5-trimethoxybenzaldehyde cyanohydrin acetate. The reduction was successful using a less active palladium black and absolute ethanol as solvent. Mescaline was finally isolated as the sulphate.
Based on the weight of kiln-dried wood, the overall yields were 1% for E. Tegnans and 0.7% for the other two species. As the synthetic route is comparatively simple, it would appear that eucalypt sawdust can be used for the economic production of mescaline on a large scale.