Nitrostyrene synthesis

SYNTHESIS (from piperonal) To a solution of 15.0 g piperonal in 80 mL glacial acetic acid there was added 15 mL nitroethane followed by 10 g cyclohexylamine. The mixture was held at steam-bath temperature for 6 h, diluted with 10 mL H20, seeded with a crystal of product, and cooled overnight at 10 °C. The bright yellow crystals were removed by filtration, and air dried to yield 10.7 g of 1-(3,4-methylenedioxyphenyl)-2-nitropropene with a mp of 93-94 °C. This was raised to 97-98 °C by recrystallization from acetic acid. The more conventional efforts of nitrostyrene synthesis using an excess of nitroethane as a solvent and anhydrous ammonium acetate as the base, gives impure product in very poor yields. The nitrostyrene has been successfully made from the components in cold MeOH, with aqueous NaOH as the base. 

The more conventional efforts of nitrostyrene synthesis using an excess of nitroethane as a solvent and anhydrous ammonium acetate as the base, gives impure product in very poor yields. The nitrostyrene has been successfully made from the components in cold MeOH, with aqueous NaOH as the base. 

I have used the term "scrudge" in this and other recipes, without defining it. With this aldehyde, as with most aldehydes in this nitrostyrene synthesis reaction where there is no ortho-substituent on the benzaldehyde, the reaction progress should be carefully followed by thin-layer chromatography. As the aldehyde disappears from the reaction mixture, the nitrostyrene appears, but there is usually the development of one or more slower moving components as seen by TLC. 

Chapter IV. a-Chloromethylnaphthalene (IV,23) benzylamine (Gabriel synthesis) (IV,39) i r.N -dialkylanilines (from amines and trialkyl orthophosphates) (IV,42) a-naphthaldehyde (Sommelet reaction) (IV,120) a-phenyl-cinnamic acid (Perkin reaction using triethylamine) (IV,124) p-nitrostyrene (IV,129) p-bromonaphthalene and p naphthoic acid (from 2 naphthylamine-1 -sulphonic acid) (IV,62 and IV,164) diphenic acid (from phenanthrene) (IV,165). 

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

The Batcho-Leimgruber indole synthesis involves the condensation of o-nitrotoluene derivatives 1 with formamide acetals 2, followed by reduction of the trans-p-dimethylamino-2-nitrostyrene 3 which results to furnish indole derivatives represented by... 

In 1971, Batcho and Leimgruber introduced a new method for the synthesis of indoles. For example, condensation of o-nitrotoluene (5) with N,N-dimethylformamide dimethyl acetal (6) (DMFDMA) was followed by reduction of the rrans-P-dimethylamino-2-nitrostyrene (7) which resulted to provide the indole (8). ... 

In the synthesis of chuangxinmycin, Kozikowsld et al. employed the potassium salt of the acid 23 to condense with DMFDMA 6 to obtain the P-nitrostyrene 24 with the... 

A somewhat more complex application of this notion is represented by the CNS stimulant fencamfine (83). Diels-Alder addition of cyclopentadiene and nitrostyrene affords the norbomene derivative, 80. Catalytic hydrogenation reduces both the remaining double bond and the nitro group (81). ° Condensation with acetaldehyde gives the corresponding imine (82) a second reduction step completes the synthesis of fencamfine (83). ... 

Enandoselecdve synthesis of the anddepressant rohpram can be done by the asymmetric Michael addidon of the enolate of iV-acetyloxa2ohdone to nitrostyrene, Chiially branched pyrrohdones like rohpram are highly acdve anddepressants v/ith novel postsynapdc modes of acdon. The synthesis is shown in Scheme 4,13, ... 

The Batcho indole synthesis involves the conversion of an o-nitrotolnene to a fi-dialkyl-amino-o-nitrostyrene v/ith dimethylformairude acetM, followed by redncdve cychzadon to indoles. This provides a nsefid strategy for synthesis of snbsdtuted indoles fEq. 10.49. ... 

Pdlldclium-medidted methylencyclopeiUdne dnneUtion of nitrostyrene is used for d total synthesis of cephalotdxine, which is the predomindnt ilkaloid of the cephaldtdxus species fScheme 10.25. "... 

The first reported electroorganic synthesis of a sizeable amount of material at a modified electrode, in 1982, was the reduction of 1,2-dihaloalkanes at p-nitrostyrene coated platinum electrodes to give alkenes. The preparation of stilbene was conducted on a 20 pmol scale with reported turnover numbers approaching 1 x 10. The idea of mediated electrochemistry has more frequently been pursued for inorganic electrode reactions, notably the reduction of oxygen which is of eminent importance for fuel cell cathodes Almost 20 contributions on oxygen reduction at modified... 

The versatility of the INOC reaction is evident from the synthesis of tetrahy-drofurans fused to an isoxazoline 22a-f (Eq. 3) [181. a-Allyloxyaldoximes 21, formed by the reduction of jS-nitrostyrenes 19 with SnCl2 2H2O in the presence of an unsaturated alcohol 20, are transformed to isoxazolines 22 in high yield on treatment with NaOCl via stereoselective ring closure of a nitrile oxide intermediate (Table 2). 

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... 

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... 

The direct conversion of styrene to P-nitrostyrene using clay doped with nitrate salts has been reported. Styrene and clayfen (iron nitrate on clay) or clayan (ammonium nitrate on clay) are mixed well and then heated at 100-110 °C in solid state to give P-nitrostyrene in 68% yield.551 A more simple one-pot synthesis of P-nitrostyrene from styrene has been reported P-nitrostyrene is prepared in 47% yield on treatment of styrene with CuO HBF4,12, andNaN02 in MeCN at room temperature.55b... 

The synthetic applications of this reagent to the synthesis of nitroalkenes have been known since the 1960s.60 Nitration of alkenes with nitryl iodide, generated in situ from iodine and silver nitrite, is convenient for the synthesis of P-nitrostyrenes with various functional groups.61 This method is applied to the synthesis of ortho-methoxylated phenylisopropylamines, which are potent serotonine agonists (Eq. 2.31).62... 

Various variants of this process are presented for pyrrole synthesis. For example, reactions of 1,3-dicarbonyl compounds with P-nitrostyrene followed by treatment with amines give 3-acylpyrroles (Eq. 10.5).7... 

Palladium-mediated methylencyclopentane annelation of nitrostyrene is used for a total synthesis of cephalotaxine, which is the predominant alkaloid of the cephalataxus species (Scheme 10.25).133... 

Solid-state synthesis of /J-nitrostyrenes has been reported by Varma et al. in a process that uses readily available styrene and its substituted derivatives and inexpensive clay-supported nitrate salts, clayfen and clayan (Scheme 6.50) [170], In a simple experiment, admixed styrene with clayfen or clayan is irradiated in a MW oven (-100-110 °C, 3 min) or heated in an oil bath (-100-110 °C, 15 min). For clayan intermittent heating is recommended with 30-s intervals to maintain the temperature below 60-70 °C. Remarkably, the reaction proceeds only in solid state and leads to the formation of polymeric products in organic solvent. 

Several investigators have developed the reductive cyclization of o-nitrostyrenes into an efficient synthesis of indoles. Thus, research by the groups of Watanabe [458, 459], Sbderberg [460, 461], and Cenini [462, 463] have established this reductive Pd-catalyzed AMieteroannulation reaction as a viable route to simple indoles and fused indoles (372) as shown below. Ohta... 

Scheme 11. Deracemization of p-nitrostyrene oxide and application to the synthesis of (R)-nifenalol...

This first synthesis is easy, cheap and produces large amounts of easy to reduce nitrostyrenes. 

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. 

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