Oh my I would like to have this 4-dimethoxy butanol ! Can someone find a nice ref without those paladium salt!
(BTW good work Antoncho and Rhod! I think this tryptamine synth is one of the best (the other one as not been posted here now AFAIK, I will change that very soon!
STAY TUNED! HINT: check this patent: Patent FR2261271
or
Patent DE2344919
) if we can have an easy synth of this aldehyde)
The route I am thinking now start from 4-chloro-butyronitrile, accessible and not to expensive, (although the chlorobutyrylchloride is the more cheap starting material AFAIK (Oh can someone find a good ref without all this hard to do reduction of this acid chloride!)), and reducting the nitrile to the aldehyde with stannous chloride. The yield are usually quantitative, but I have no clue if it work with a molecule chlorinated like this 4-chlorobutyronitrile. Another synthesis of indole is discussed here too.
Here we go:
A New Synthesis of Aldehydes. - By HENRY STEPHEN. (Can't give the ref, sorry!
)
The ref is possibly J.Chem.Soc. 127, 1874 (1925) /RhodiumTHE basis of this new method is the conversion of a nitrile through the imino-chloride (which need not be isolated) into an aldehyde with the same number of carbon atoms. The most suitable reducing agent is anhydrous stannous chloride
* dissolved in ether saturated with hydrogen chloride. Finely powdered, anhydrous stannous chloride (1.5 moIs.) is suspended in dry ether, which is then saturated with dry hydrogen chloride until the mixture separates into two layers, the lower viscous layer consisting of stannous chloride dissolved in ethereal hydrogen chloride. The nitrile (I mol.) is now added with vigorous shaking and, after a few minutes, separation begins of a white, crystalline aldimine stannichloride, (R-CH=NH,HCI)2,SnCI4.
The course of the formation and reduction of the imino-chloride is therefore as follows: R-CN + HCl -> R-CCl=NH; R-CCl=NH + SnCl2 + 2HCl -> R-CH=NH,HCl + SnCl4. After removal of this salt the ether may be again employed for another preparation. The salt is readily hydrolysed by warm water, and the aldehyde formed may be removed by distillation with steam or extraction with a solvent.
The method is applicable to aliphatic and aromatic nitriles, and the yields are usually almost quantitative. As the rate of deposition of the stannichloride varies in different cases, it is advantageous to allow at Ieast two hours for completion of the reaction.
3,4,5-Trimethoxybenzonitrile and other nitriles which are only sparingly soluble in cold ether may be dissolved in chloroform and the solution added to the reducing agent.
o-Toluonitrile and alpha-naphthonitrile give only small yields of the respective aldehydes. This is no doubt due to steric hindrance, of which the two nitriles form well known examples; both, for instance, fail to give imino-ethers (Pinner, " Die Imidoäther und ihre Derivate," 1892, pp. 4,81), for the formation of which an imino-chloride is essential.
A special application of the method is the formation of
indole by reduction of o-nitrophenylacetonitrile; sufficient reducing agent is employed to reduce both the imino-chloride and the nitro-group :
(nice picture : the o-nitrophenylacetonitrile is transformed in the amino-aldehyde which cyclise to indole)
(compare Pschorr, BeT., 1910, 43, 2543).
Experimental
n-Octaldehyde: Octonitrile was prepared by warming a solution of octoamide in thionyl chloride on the waterbath for 30 minutes and removing the excess of thionyl chloride under diminished pressure. The residue of nitrile (b. p. 87° /10 mm.) was almost pure and the yield quantitative. The method has been applied to the amides of myristic, palmitic, and stearic acids with equally good results.
Octonitrile (25 g.) was brought into reaction with stannous chloride (57 g.) in dry ether (200 c.c.), saturated with hydrogen chloride as described above. The aldehyde produced by hydrolysis of the stannichloride was isolated by distillation with steam and extraction with ether. It was obtained as a colourless oil, b. p. 65°/11 mm., having a strong lemon-like odour. Prepared by the usual methods and crystallised from methyl alcohol, the oxime was obtained in fine, silky needles, mp. 60°, the semicarbazone in needles, mp 98°, and the p-nitrophenylhydTazone in bright yellow needles, mp 80°.
* The anhydrous stannous chloride for these reactions was prepared by heating the crystalline variety until the temperature reached 180°. The product contained some stannous oxide, but this appears to be insoluble in ether saturated with hydrogen chloride. A convenient and rapid method for preparing pure anhydrous stannous chloride is to dissolve the fused mass obtained as above in pyridine. Solution takes place with evolution of heat and the insoluble stannous oxide is then filtered off. Tho filtrate deposits fine, white needles of a double compound, SnCl2,2C5H5N. When the double compound is heated under diminished pressure the pyridine is removed ; the residue is anhydrous stannous chloride.