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Henry condensation at high pressure (METHYL-J)
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From the tundra of Siberia, Stalin brings you an article requested by comrade Rhodium (Post 217986 (Rhodium: "Wanted references", Novel Discourse)):
NE Azafonov, IP Sdishev, VM Zhulin. Henry condensation at high pressures. 1. Synthesis of 1-(3,4-methylenedioxyphenyl)-2-nitro-1-butene and an improved synthesis of 1-(3,4-methylenedioxyphenyl)-2-methylaminobutane. Bull Acad Sci USSR Div Chem Sci (Eng Trans) 39 (1990) 738-741.
Shostakovich' 11th Symphony (The Year 1905) is a good choice to guide you through the text. Some background information on METHYL-J can be found under PIHKAL #128 ( http://www.erowid.org/library/books_online/pihkal/pihkal128.shtml ).
NE Azafonov, IP Sedishev, VM Zhulin.
1. SYNTHESIS OF 1-(3,4-METHYLENEDIOXYPHENYL)-2-NITRO-1-BUTENE AND AN IMPROVED SYNTHESIS OF 1-(3,4-METHYLENEDIOXYPHENYL)-2-METHYLAMINOBUTANE
Abstract: The hitherto inaccessible nitroolefin (VII), which is the most convenient intermediate for the synthesis of the psychotropic amine (VIII), has been obtained by the direct condensation at high pressures (up to 1500 MPa) of piperonal (V) with 1-nitropropane (VI). The structure of (VII) was confirmed by direct synthesis from pyrocatechol (X). The amine (VIII) was obtained in three steps from (VII). This synthesis of (VIII) is shorter than that previously reported.
The condensation of aromatic aldehydes (I) with nitroalkanes (II) to give β-nitrostyrenes (III) (the Henry reaction) is an important step in the synthesis of β-phenylethylamines and their analogs (IV), which are biogenic amines. With some (I) and (II), however, the yields of (III) are too low, which makes the preparation of compounds (IV) by this method difficult :
The principal aim of the present investigation was to examine the factors governing the condensation of piperonal (V) with 1-nitropropane (VI), which, according to literature reports, is too slow, gives large amounds of by-products, and is suitable for the preparation of large amounts of the required (VII) . The development of a simple route for the preparation of (VII) from (V) and (VI) is important, since (VII) is the most convenient intermediate for the preparation of (VIII), a compound having unique psychopharmacological properties, and which is currently obtained by a rather laborious, multistage process . For this reason, the direct synthesis of (VIII) from (VII) is of great practical interest:
Aldol-crotonic condensations are known to be accelerated considerably by pressure . It would therefore be expected that it would also modify the rate of the reaction of (V) with (VI), so that the preparation of (VII) in preparative quantities might prove possible.
Our studies of the condensation of (V) with (VI) have shown (Table 1) that pressure does indeed markedly accelerate this reaction and, in addition, improves its selectivity, under optimum conditions (experiment 25, Table 1), the yield of (VII) reaching 65%. The effect of pressure on the yield of (VII) is well shown by a series of experiments (Table 1, expts 1-15, and Fig 1), carried out at the same temperature and time of reaction of (V) with (VI). The broken lines (a and b) in Fig 1 indicate the phase transition pressures (due primarily to crystallization of the acetic acid) in the system (V) + (VI) + AcOH + AcONH4, as found from the decrease in volume of the mixture near these pressures . As will be seen from Fig 1, in the crystallization region the yield of (VII) increases, but on further increase in pressure the change is not as great. At 50°C, the yield curve shows a maximum at around 1200 MPa due, it appears, to further changes in the phase state of the system.
The solvent and catalyst used also have a considerable influence on the yield of (VII). The best catalysts were primary amines, and the best solvent acetic acid. The selectivity of the condensation of (V) with (VI) at high pressures usually increased, but it did not prove possible to eliminate entirely undesirable reactions, which always occurred, especially at elevated temperatures. One of the by-products, 3,4-methylenedioxybenzonitrile (IX), isolated by column chromatography and identical with that described, is probably formed, like other nitriles, from aromatic aldehydes and (VI) .
The structure of (VII) was also confirmed by another, more laborious synthesis (X) -> ... -> (VII). The physicochemical properties of the (VII) obtained by the two methods were identical.
The availability of (VII) enabled us to develop a simple, three-step synthesis of (VIII) involving reduction of (VII) with LiAlH4, formulation of the amino-group and subsequent reduction with LiAlH4. Isolation of the compounds at the intermediate stages was unnecessary. The physicochemical properties of (VIII) were in agreement with those reported . The availability of (VII) by direct condensation of (V) with (VI) therefore makes this method for the synthesis of (VIII) more convenient than that reported previously .
Experimental: Melting points were determined on a Boetius hot plate. PMR spectra were obtained on Bruker WM-250 and Jeol 90 FQ spectrometers, in chloroform (internal standard HDMS). Chemical shifts are given on the δ scale relative to TMS (δ HDMS = 0.055 ppm). 13C NMR spectra were obtained on a Bruker AM-300 (in chloroform, δ from TMS), and mass spectra on a Varian MAT CH-6.
 CB Gairaud e.a JOC 18 (1953) 1
 DE Nichols e.a JMC 29 (1986) 1009
 K Matsumoto e.a. Synthesis (1985) 1
 VM Zhulin e.a. Vysokomol Soedin A24 (1982) 2621
 HM Blatter e.a. JACS 83 (1961) 2203
 E Schmidt e.a. Chem Ber 53 (1920) 1529
 W Bonthrone e.a. JCS C (1969) 1202
 WJ Gensler e.a. JOC 23 (1958) 908
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