4-nitrostyrene

In a 6-1. wide-mouth bottle, packed in a pail with a freezing mixture of ice and salt and fitted with a mechanical stirrer, a thermometer and a separatory funnel, are placed 305 g. (5 moles) of nitromethane (Org. Syn. 3, 83) 530 g. (5 moles) of benzalde-hyde (Note 1) and 1000 cc. of methyl alcohol. A solution of sodium hydroxide is prepared by dissolving 210 g. (5.25 moles) of caustic soda in approximately an equal volume of water and cooling. It is then diluted to 500 cc. with- ice and water, poured into the funnel, and added with stirring to the nitromethane mixture at such a rate that the temperature is kept at 10-15° (Notes 2 and 3). 

A bulky white precipitate forms rapidly during the addition of the alkali. The mixture gets so thick that stirring becomes difficult and it may be advisable to add 100 cc. more of methyl alcohol. After fifteen minutes standing, the pasty mass is converted to a clear solution by the addition of 3-3.5 1. of ice water containing crushed ice (Note 4). Hydrochloric acid (made by diluting 1000 cc. of concentrated hydrochloric acid with 1500 cc. of water) is placed in a 15-I. mixing jar and the reaction mixture run into this from the separatory funnel at such a rate that the stream just fails to break into drops (Note 5). A pale 

Technical benzaldehyde which had been washed with sodium carbonate solution, dried and distilled under reduced pressure, was used in this preparation. 

The first few cubic centimeters of sodium hydroxide solution should be added cautiously to the nitromethane mixture since, after a short induction period, there is a considerable evolution of heat and the temperature may rise from —10° to 30° or even higher in spite of good stirring. If necessary, this rise in temperature is easily checked by adding a handful of crushed ice directly to the mixture. After this initial reaction the rest of the alkali may be added more rapidly. 

The condensation induced by sodium hydroxide is almost instantaneous above 10°. The procedure may be interrupted with safety after the addition of alkali, and the product will not change on standing overnight in an ice chest. 

Checked by Richard T. Arnold, William E. Parham, and Darwin D. Davis. 

m-Nitrocinnamic acid. In a 1-1. round-bottomed flask fitted with a reflux condenser are placed 151 g. (1 mole) of m-nitro-benzaldehyde (Note 1), 115 g. (1.1 moles) of malonic acid, 250 ml. of 95% ethanol, and 25 ml. of pyridine. The mixture is heated on a steam bath under gentle reflux for 6-8 hours and cooled. The large masses of crystals are broken up with a spatula, and the reaction mixture is cooled in an ice bath. The solid is collected on a Buchner funnel, and the residue is washed with 100 ml. of cold ethanol and then with two 100-ml. portions of diethyl ether. The crude f -nitrocinnamic acid is suspended in 300 ml. of ethanol and digested on a steam plate for 2-3 hours. The mixture is cooled and filtered, and the solid is air-dried. The product, 144-155 g. (75-80%), is a light-yellow solid and melts at 200-201° (Note 2). 

m-Nitrostyrene. In a 250-ml. two-necked flask equipped with a 250° thermometer and an air condenser are placed 30 g. (0.155 mole) of jw-nitrocinnamic acid, 2 g. of copper powder, and 60 ml. of dry quinoline (Note 3). The flask is heated with a Bunsen burner to 185-195°, during which time a steady stream of carbon dioxide is evolved. After 2-3 hours (Note 4), the reaction mixture is cooled and poured into a mixture of 75 ml. of concentrated hydrochloric acid and 175 g. of ice. The t-nitro-styrene is isolated by steam distillation, approximately 1 1. of 

This procedure has been used by the submitters and others to prepare the following cinnamic acids from substituted benzal-dehydes o-nitrodnnamic acid (70%),2 / -nitrocinnamic acid (77%),2 m-cyanocinnamic acid (71%),3 o-chlorocinnamic acid (82%),4 m-chlorocinnamic acid (53%),4 -chlorocinnamic acid (73%),4 2,4-dichlorocinnamic acid (70%),4 3,4-dichlorocinnamic acid (81%),4 w-bromocinnamic acid (31%),4 / -methoxycinnamic acid (60%),4 and 3,4-dimethoxycinnamic acid (77%).4 

The method constitutes a simple preparation of ethanol-in-soluble cinnamic acids, of a high degree of purity when compared with the Perkin reaction 6 or the usual procedure for the Doebner reaction,6 which uses a large excess of pyridine. A useful modification of this reaction is to warm the reactants on a steam plate in the absence of alcohol.7-8 

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Similar cycloaddition reactions were observed with methyl vinyl sulfone (48) and )3-nitrostyrene (48,51). Methyl vinyl ketone, on the other hand, is reported to give dihydropyrans as the initial products (50,52,53). Thus (16) on reaction with methyl vinyl ketone at room temperature for 12 hr gave a 60% yield of 2-dimethylamino-3,3,6-trimethyl-3,4-dihydro-2H-pyran (59). 

The reaction between the pyrrolidine enamine of butyraldehyde (52) and )3-nitrostyrene (53) provides cyclobutane adduct 54 quantitatively in either petroleum ether or acetonitrile solvent, but in the more polar ethanol solvent a 2 1 condensation product occurred. The structure of the product was shown to be 55 (57). 

Nitrostyrene requires from 60-90 hours for the uptake of 1 mole of hydrogen. The product, l-phenyl-2-nitroethane, is purified by distillation, bp 76-7770.5 mm. 

A strategy involving sequential 1,3-dipolar cycloadditions has been reported for the synthesis of novel bis-isoxazolo substituted piperidines 192a and 192b (Eqs. 18 and 19) [53]. It consists of the Michael addition of an unsaturated alkox-ide 185 to )3-nitrostyrene 184 followed by an INOC or ISOC reaction to provide isoxazolines 187-189 (Eq. 18 and Table 18). A polymer supported acyl chloride... 

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. 

Enantioselective additions of (3-dicarbonyl compounds to (3-nitrostyrenes have been achieved using to-oxazolidine catalysts. This method was used in an enantioselective synthesis of the antidepressant drug rolipram.325... 

Nitrostyrene reacts with allylzinc reagents in dry DMF at room temperature to give the addition products in excellent yield (Eq. 4.80).102 The reaction of allyl tin compounds or allyl silanes with nitroalkenes requires the assistance of Lewis acids to give the addition products in good yield (Eq. 4.81).103... 

Westcott et al. have also observed the exclusive Mnear product 3-02NC,5H4CH2CH2Bcat in the hydroboration of 3-nitrostyrene by [lrCl2(T -C5Me5)]2 and HBcat [45]. Similarly, the Hnear isomer 4-(Bcat)2NC6H4CH2CH2Bcat could be preferentially obtained in the iridium-mediated hydroboration of 4-vinylaniline as an example of a mild route to anihne derivatives containing boronate esters. Westcott et al. claimed a mechanism that may not necessarily proceed via conventional pathways that invoke initial oxidative addition of HBcat to the metal center. 

The reduction of /3-nitrostyrenes with indium metal in aqueous ammonium chloride gave a mixture of E and Z isomers while the reduction of -methyl-/ -nitrostyrenes with indium powder in the presence of trimethylsilyl chloride gave exclusively the E isomer. 

The Takemoto group synthesized a series ofdiaminocyclohexane-based thiourea derivatives (e.g., 12, 40, 57, and 58) for catalysis of the Michael addition [149-152] ofmalonates to trons-j3-nitrostyrenes (Figure 6.18) [129, 207]. In the model, Michael addition of diethyl malonate to trons-]3-nitrostyrene at room temperature and in toluene as the solvent tertiary amine-functionalized thiourea 12 (10mol% loading) was identified to be the most efficient catalyst in terms of catalytic activity (86%... 

Scheme 6.105 Asymmetric Michael addition of phenylpropionaldehyde to trar)s- 3-nitrostyrene catalyzed by primary amine thioureas 102, 104, and 105.

Figure 6.38 Cinchonine-derived thioureas (10mol% loading) screened in the Michael reaction of dimethyl malonate to trans- 3-nitrostyrene.

Ramamoorthy et al. (444) found that a-phenyl-A-(4-methylphenyl)nitrone can be the guest molecule in inclusion complexes with a p-cyclodextrin host in 1 1 and 1 2 ratios (guest/host), and that the latter undergoes a 1,3-dipolar cycloaddition reaction with electron-deficient alkenes. In more recent work, they have formed 1 1 inclusion complexes of the bowl-shaped p-cyclodextrin 383 with (3-nitrostyrene 381 or 1-nitrocyclohexene 382, which leave the alkene moiety exposed (Fig. 1.9) (445). Complexes 381 and 382 undergo cycloaddition reaction with ot-phenyl-A-(4-methylphenyl)nitrone in the solid state after thorough homogenization (60 °C, 3 h) to give the 4-substituted products exclusively in 80 and 85% yield, respectively. 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

Nitrostyrene [102-96-5] M 149.2, m 60°. Crystd from absolute EtOH, or three times from benzene/pet ether (b 60-80°) (1 1). 

Nitrosamines, 1074, 1076 Nitrosobenzene, 629, 630 Nitroso compounds, table of, 1085 p-Nitroso derivatives, 660 N-Nitrosodiethylamine, 426 N-Nitrosodimethylamine, 426 p-Nitrosodimetlivlaniline, 562,573 N-Nitrosoethylaniline, 570 N-Nitrosomethylaniline, 562. 563, 570 p-Nitroso-N-methylanOine, 563, 574 Nitrosomethylurea. 968, 969 a-Nitroso-(3-naphthol, 958 (3-Nitrostyrene, 709, 717 a(3-Nonenoic acid, 405, 468 -Nonoic acid. 487... 

Cycloaddition using the unusually functionalized 2-diazo-1,1,1-trifluoro-3-nitropropane (15) could be achieved with methyl acrylate, methacrylic acid chloride, and esters (Scheme 8.5), but not with the 1,2-disubstituted C=C bonds of (3-nitrostyrene, ethyl cinnamate, and 4-methyl-3-penten-2-one (42). In these cycloadditions, 15 is considerably less reactive than 2-diazo-1,1,1-trifluoroethane... 

N 18.67% wh ndls (from hexane), mp 87-88° was prepd by adding nitroform to a soln of (3-nitrostyrene in MeOH, addg w heating at 40° for 4 hrs, and cooling filtering the product. 

The present procedure is a general method for preparing aromatic and heterocyclic aldehydes. It is of particular value in the synthesis of o-nitrobenzaldehydes in 100-200 g. lots. The benzaldehydes are useful starting materials for cinnamic acids, /3-nitrostyrenes, etc. The manipulations are simple, the yields are reproducible, and the intermediates can be easily isolated and purified. The intermediates themselves have many synthetic uses. 

The alkylation of the chiral enamine (172) by 3-nitrostyrenes gives diastereomerically pure Michael adducts (173) with high ee (Scheme 62).182 Comparable selectivities were observed with a-(methoxycar-bonyl)cinnamates as substrates.183 The same method was used for the enantioselective alkylation of -tetralones in the 3-position by p-nitrostyrenes.184... 

The isomeric triazoles do not arise from a lack of regioselectivity in azide addition to /3-nitrostyrenes as shown in Scheme 77155-294,295 instead, an initial isomerization of the nitroolefin followed by regioselective azide addition to the olefinic isomers has been proposed (Scheme 128).284-297 The... 

In the reaction of piperidine with (3-nitrostyrenes, Equation (47), k0 for the reactions of the... 

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