2-Bromo-2-nitrostyrene

Recently, j3-bromo-()-nitrostyrene has been successfully involved in the ISOC process (Scheme 3.143) (390). 

It is noteworthy that the PhS-/MeO- rate ratios are not much different for the unreactive j8-bromo- -nitrostyrene and its very reactive 2,4-dinitro analogue, being 4000 and 13,000, respectively. 

Phenyl azide reacts with /J-bromo-/ -nitrostyrene (76 Ar = Ph) to give 1,5-diphenyl-4-nitro-l,2,3-triazole (77 Ar = R = Ph).67 Similarly, bromonitro-styrenes and sodium azide give the nitrotriazoles 77 (R = H) [Eq. (24)].68... 

Introduction of an o-nitro group into the mildly reactive cis and trans-j8-bromo- -nitrostyrenes increases the rate with PhS ion 3400 and 41,500... 

Reactions of the enamine derived from cyclohexanone and prolinol methyl ether with /(-nitrostyrenes have been described by Seebach and co-workers (Scheme 20, Table 6) (33,44). This procedure uniformly provides the syn diastereomer as the exclusive detectable product. With the exception of the 2-bromo-/ -nitrostyrene in entry 4, enantiomeric excesses of > 92% are observed. 

Bromo nitrostyrene bis(trichloromethyl) sulphone N-alkyl dimethylbenzyl ammonium chloride Benzothiazole-2-thiol... 

Soderberg and coworkers have developed a palladium-phosphine-catalyzed reductive iV-het-eroannuladon of 2-nitrostyrenes forming indoles in good yields For example, reaction of 6-bromo-2-nitrostyrene with carbon monoxide in the presence of a catalytic amount of palladium diacetate (6 mol% and triphenylphosphine 124 mol% in acetonitrile at 30 gives 4-bromoindole in 86% yield fEq 10 62 Several functional groups, such as esters, ethers, bromides, tnflates, and additional nitro groups, have been shown to be compatible with the reaction conditions... 

Bromo-j3-nitrostyrene and triphenylphosphine in dry benzene gave the phosphonium bromide (47). Using methanol as the solvent, the rearranged product (48) was formed, possibly via an azirine intermediate. Substituted -bromo-/3-nitrostyrenes yield the phosphoranes (49) and a phosphonium salt. When the aryl group is electron-donating, the reaction follows a different course to form the styrene (50) by initial attack of the phosphine on halogen. 

The elimination of HBr from ds-yS-bromo-p-nitrostyrene [155] producing the acetylene [156], has been studied by Naso and Ronzini (1974) using KF as the base (25). Their results (Table 43) show that the rate enhancement due to the... 

Fluoride-promoted elimination of HBr from eis-/ -bromo-p-nitrostyrene [1551 under solid-liquid conditions ... 

Bromo-2,5-Dimethoxyamphetamine, This should be prepared by reducing the above nitro-propene with LAH as described below. Other reductions may or may not be compatible with the electronic character of the bromine atom. This particular reduction can also be used to reduce most any nitrostyrene, nitrobenzene, etc. Note These will work too, CPB, 16, 217 or JACS, 72, 2781, also found in this book. 

Bromo-4,5-methylenedioxy-B-nitrostyrene. A solution of 64 g bromopiperonal, 65 g nitromethane (or analog), and 30 g of NH4OAC in 400 ml of AcOH, is heated to reflux for 2 hours. Cool and pour the mixture into 1 liter of water. This will precipitate a crystal solid that is removed by filtration and recrystallized from CHCf-EtOH (50% by volume) to give the product. Yield 55 g, mp 160-161°. 

To reduce to the active formula, see the zinc reduction as given in the reduction section, CPB, 16, 217 (1968). This reduction is specifically matched to 3-bromo-4,5-methylenedioxy-B-nitrostyrene and other highly substituted ring type styrenes and propenes. Zinc reductions carried out properly are very gentle and do not destroy delicate ring substituents, while some reductions do. Zinc reductions can reduce any nitrostyrene or propenes, but some of these compounds must use the zinc reduction. Which compounds Compounds with lots of ring substituents, like 2,5-dimethoxymethylenedioxy, 3-methoxy-4-0-carbethoxy, etc. This is not to say that some of the other reductions are not capable of gentle reductions. 

SYNTHESIS To a vigorously stirred suspension of 2.1 g 4-bromo-2,5-dimethoxy-B-nitrostyrene [from 4-bromo-2,5-dimethoxybenzaldehyde and nitromethane in acetic acid with ammonium acetate as a catalyst, mp 157-158 °C, anal. (C 0H]0BrNO )... 

The reactivity of the halide ions could not be evaluated directly since they have not been studied with the same substrate. However, -toluene-thiolate ion is nine orders of magnitude more reactive than chloride ion towards 2-chloro-l,l-diarylethylenes in dimethylformamide. Although comparison may not be justified (see below), a similar reactivity ratio exists for the reactions of j8-bromo-j -nitrostyrene with iodide ion in butyl cellosolve and thiophenoxide ion in methanol. Bromide ion is 0-6 times as reactive as chloride ion towards l-anisyl-l-phenyl-2-chloroethylene. These relative reactivities of the halide ions should be regarded only as rough estimates. Their very low reactivity is also shown by the chloride exchange in ethyl /3-chlorocrotonate, which is at least 106 times slower than the substitution by thioethoxide ion (Jones et al., 1960) while trichloroethylene does not exchange at all even at 245° (Bantysh et al., 1962). 

Based on relative reactivities towards diarylchloroethylenes and jS-bromo-p-nitrostyrenes. 

The first reported synthesis of MDMA was from safrole by converting it to its bromo derivative followed by reaction with meth-ylamine (Biniecki et al., 1960). Bailey et al. describe the synthesis of MDMA from 3,4-methylenedioxyphenylacetone using a Leuckart reaction with N-methylformamide and hydrolysis of the N-formyl derivative (Bailey et al., 1975). A third synthesis for MDMA described in the literature starts with peperonal which is reacted with nitroethane, ammonium acetate, and acetic acid to form a nitrostyrene derivative that is reduced to the ketone and then reacted with methylamine to form MDMA (Rabjohns, 1963). Using the method of Borch et al., MDMA can be synthesized by the reductive amination of the appropriate ketone in the presence of sodium cyanoborohydride (Borch et al., 1971). The MDMA syntheses used in clandestine laboratories are analogous. 

Table IV compares the reactivity ratios of a soft (PhS-) to a hard (MeO-) nucleophile in vinylic substitution. PhS is always more reactive, and ratios lower than unity, as for 4, X = Br (4), are certainly due to elimination-addition with MeO . The ratios change by >2000-fold and are sensitive to the geometry of the substrate. An important feature is that for (3-halo-p-nitrostyrenes the ratio decreases strongly with the increased hardness of the (3-halogen (38). The lowest ratios are for the (3-fluoro derivative, whereas the differences between the chloro and bromo compounds are not so large. This behavior is similar to that in SNAr reactions. This behavior can be rationalized by symbiotic effects, which favor the soft-soft PhS--Br interaction and the hard-hard MeO-F interaction. A reactivity-selectivity relationship for vinyl bromides of different electrophilicities does not exist.

The yields of nitro-1,2,3-triazoles are not usually high, but such products are useful intermediates in the preparation of many of the compounds previously discussed. For example, /3-nitrostyrenes or enamines provide routes to the 4-amino compounds that are difficult to obtain by other methods (Eqs. 10 to 12).When R = H, the yields are vastly superior. A still more promising route involves -bromo-/3-nitrostyrenes (Eq. 13). ... 

SYNTHESIS To a vigorously stirred suspension of 2.1 g 4-bromo-2,5-dimethoxy-beta-nitrostyrene [from 4-bromo-2,5-dimethoxybenzaldehyde and nitromethane in acetic acid with ammonium acetate as a catalyst, mp 157-158 °C, anal. (C10H10BrNO4) C,H] in 20 mL anhydrous MeOH, there was added a solution of sodium methoxide in MeOH (generated from 0.5 g metallic sodium in 20 mL anhydrous MeOH). After a [3D. mol structure] there was added 10 mL acetic acid (no solids... 

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