Nitrostyrenes precursors

Reductive cyclization of nitrostyrene precursors has also proven to be a useful route to 5,6-dihydroxyindole and its derivatives, as illustrated by the efficient preparation of the system 32 (Scheme 18) <1999S793>. A general synthetic approach to indoles involves a palladium-catalyzed reductive cyclization of 2-nitrostyrenes <1997JOC5838>. This procedure was used in the synthesis of several natural products, e.g., 4-(methoxymethyl)-2-methylindole 33 (Scheme 19), a constituent of a tricholoma species <1999JOC9731, CHEC-III(3.03.2)282>. 

Reductive cyclization of nitrostyrene precursors has also proven to be a useful route to 5,6-dihydroxyindole and its derivatives, as illustrated by the efficient preparation of the system 123 (Equation 32) <1999S793>. 

A number of ARIADNE analogues have been made, or at least started, purely to serve as probes into whatever new areas of psychopharmacological activity might be uncovered. One of these is a HOT compound, and one is a TOM compound, and a couple of them are the pseudo (or near-pseudo) orientations. The HOT analogue was made from the nitrostyrene precursor to... 

We report a vibrational spectroscopic study of several yS-methyl-y nitrostyrene derivatives that are important intermediates in the synthesis of illicit amphetamine-like drugs, such as 3,4-methylenedioxymethamphetamine ( ecstasy or MDMA), 3,4-methylene-dioxyamphetamine (MDA), 4-methyl-thioamphetamine (MTA) and 4-methoxyamphetamine (PMA). A complete vibrational analysis of these systems was carried out by Raman spectroscopy and DFT calculations (103), The corresponding Raman spectra evidenced distinctive features for each of the >5-nitrostyrene precursors investigated (Figure 7), allowing their ready identification in the final product (104),... 

Hydroxy-3-methoxy-B-nitrostyrene. A mixture of methylamine hydrochloride (7 g, see precursor section for synthesis) and 10 g of sodium carbonate in 100 ml of methanol is stirred well, filtered, and added to a solution of 219 g of vanillin and 85 ml of nitromethane in 600 ml of ethanol. Keep this solution in the dark at room temp for 71 hours to make the nitrostyrene crystallize out. Filter and wash with cold methanol. Yield 225 grams, nip 166-168°. This and the other two nitriles are reduced by the method listed in the reduction section, JACS, 72, 2781. This reduction can be used to reduce many of the nitro type compounds. 

TABLE. Physical Properties of the a-Alkylmescaline Homologues and their Precursor Nitrostyrenes... 

There has been a number of developments in the use of salicylaldehydes as precursors of both chromenes and chromans. Alkenes activated by acyl, formyl, nitrile and phenylsulfonyl groups react with 2-hydroxybenzaldehydes and 2-hydroxy-1-naphthaldehyde under Bayliss-Hillman conditions to yield 3-substituted chromenes via the in situ dehydration of the initially formed chroman-4-ol <02JCS(P1)1318>. In like manner, P-nitrostyrenes yield 2- and 2,2-substituted derivatives of 3-nitrochromenes <02H(57)1033>. A simple route to 2-phenyl-2H-chromenes starting from salicylaldehyde and utilising a Pd(0)-catalysed cyclisation of an allylic acetate has been described <02SC3667>. 

Several nitrogen-containing heterocycles can be obtained by carbonylation, at high temperature and pressure, of organic nitro compounds with, in the ortho position, an unsaturated group able to interact with the presumed intermediate nitrene species.t When Ru3(CO)i2 is used as a catalyst, an intermediate imido complex similar to 4 can be suggested on the basis of what has been discussed. However, repeated attempts to synthesize such a complex by reaction of Ru3(CO)i2 with P-substituted o-nitrostyrenes (the precursors of indoles 6-Eq. 16) have so far been unsuccessful. 

The homologues of 2,4-DMA that were iodinated (or occasionally fluor-inated) were mono- or di-alkylated on the nitrogen, and the precursor that was common to all was the corresponding acetone. The above nitrostyrene, 1-(2,4-dimethoxyphenyl)-2-nitropropene, was reduced in acetic acid with elemental iron, and the base-washed extracts stripped of solvent and distilled (125-145 deg C at 0.5 mm/Hg) to give 2,4-dimethoxyphenylacetone as a water-white oil. The principal reductive amination product of this, the one that was most thoroughly explored with various halogenation schemes, was obtained by the reaction of 2,4-dimethoxyphenylacetone with dimethylamine and sodium cyanoborohydride. This product,... 

This latter nitrostyrene is the precursor to DMPEA, q.v. Anal. (C32H37N3012S2) C,H. The mother liquor above is the source of the 4-TIM nitrostyrene, and its isolation is described in the recipe for 4-TIM. 

A new acid catalyst of potential use in the Bischler-Napieralski cyclization is P2O5 in methanesulfonic acid. The phenethylamines used in isoquinoline syntheses are usually prepared from the reduction of the corresponding /S-nitrostyrenes. A more versatile procedure starts with a substituted benzyl chloride which is converted to the nitrile using sodium cyanide in DMSO (dimethylsulfoxide). Reduction of the nitrile with LiAlH4 in the presence of AICI3 gives the desired amine in excellent yield. Benzylamines or their quaternary salts may also be utilized in appropriate solvents in place of benzylic chlorides, so that they too may act as nitrile precursors. ... 

Figure 7. Experimental Raman spectra (75 -1750 cm solid state, at 298 K) for some precursors of amphetamine-like drugs 3,4-methylenedioxy-P-methyl- nitrostyrene (A) 4-methoxy-P-methyl- nitro-styrene (B) 4-methylthio-P-methyl-P-nitrostyrene (C). (The main vibrational modes are assigned Sqco ond ScH - CH (ring) and OH (ring) in-plane deformations Vsno2 2 symmetric stretching Vc-o/c-s cind Vc=c C-O/C-S and C=C stretching. The most stable calculated (B3LYP/6-31G ) geometries for each compound are also represented. (Reprinted with permission of RSC from reference 104. Copyright 2004.)...

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