Nitro reaction with alcoholates

Aromatic urethanes and dialkyl carbonates were simultaneously prepared by the reaction of aromatic nitro compounds with alcohols and carbon monoxide over a catalyst mixture containing DBU (82JAP(K)32251). 

Reaction mechanisms. We have already pointed out <4.2.6.) that in practice no studies on the mechanisms o-f the N-carbonyl at i on o-f aromatic nitro compounds with alcohols leading to carbamates have been carried out. In most cases the intermediate -formation o-f the isocyanate is very likely, and thus the reaction mechanisms are strictly related to... 

Reduction of a nitro compound to a primary amine. In a 50 ml. round-bottomed or conical flask fitted with a reflux condenser, place 1 g. of the nitro compound and 2 g. of granulated tin. Measure out 10 ml. of concentrated hydrochloric acid and add it in three equal portions to the mixtiue shake thoroughly after each addition. When the vigorous reaction subsides, heat under reflux on a water bath until the nitro compound has completely reacted (20-30 minutes). Shake the reaction mixture from time to time if the nitro compound appears to be very insoluble, add 5 ml. of alcohol. Cool the reaction mixture, and add 20-40 per cent, sodium hydroxide solution imtil the precipitate of tin hydroxide dissolves. Extract the resulting amine from the cooled solution with ether, and remove the ether by distillation. Examine the residue with regard to its solubility in 5 per cent, hydrochloric acid and its reaction with acetyl chloride or benzene-sulphonyl chloride. 

Reductive carbonylation of nitro compounds is catalyzed by various Pd catalysts. Phenyl isocyanate (93) is produced by the PdCl2-catalyzed reductive carbonylation (deoxygenation) of nitrobenzene with CO, probably via nitrene formation. Extensive studies have been carried out to develop the phosgene-free commercial process for phenyl isocyanate production from nitroben-zene[76]. Effects of various additives such as phenanthroline have been stu-died[77-79]. The co-catalysts of montmorillonite-bipyridylpalladium acetate and Ru3(CO) 2 are used for the reductive carbonylation oLnitroarenes[80,81]. Extensive studies on the reaction in alcohol to form the A -phenylurethane 94 have also been carried out[82-87]. Reaction of nitrobenzene with CO in the presence of aniline affords diphenylurea (95)[88]. 

Reaction With Carbonyl Compounds. Primary and secondary nitroparaffins undergo aldol-type reactions with a variety of aldehydes and ketones to give nitro alcohols (11). Those derived from the lower nitroparaffins and formaldehyde are available commercially (see Nitro alcohols). Nitro alcohols can be reduced to the corresponding amino alcohols (see Alkanolamines). 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Alkoxyl tion. The nucleophilic replacement of an aromatic halogen atom by an alkoxy group is an important process, especially for production of methoxy-containing iatermediates. Alkoxylation is preferred to alkylation of the phenol wherever possible, and typically iavolves the iateraction of a chloro compound, activated by a nitro group, with the appropriate alcohol ia the presence of alkaU. Careful control of alkaU concentration and temperature are essential, and formation of by-product azoxy compounds is avoided by passiag air through the reaction mixture (21). 

Conjugated nkro ilkenes are isomerized to illylic nitro compounds under basic conditions Reactions of a,fi-unsarurated nitro compounds with aldehydes under basic conditions lead directly to y, 5-unsaturated fi-nitro alcohols fEq 3 24 "This reaction is very useful for preparing illyhc nitro compounds... 

Subsequently, these authors have also studied the effect of polar factors on the sulfenate-sulfoxide equilibrium and obtained similar results to those reported by Braverman and coworkers . For example, reaction of 2,4-dinitrobenzenesulfenyl chloride with lithium allyl-a-dj alcoholate gives only (or perhaps mainly ) allyl-a-d2 2,4-dinitrobenzenesulfenate, whereas the corresponding reaction with 4-nitrobenzenesul-fenyl chloride results in complete ( > 99%) rearrangement to the sulfoxide. However, when a single nitro group is located in the ortho position, the ratio (K) of sulfenate to sulfoxide approaches unity. This ratio is also affected by the polarity of the solvent and changes from 1.43 in CCI4 to 0.39 in chloroform, consistent with the results described above for the equilibrium shown in equation 9. 

Another method for improving the reactivity of nitro compounds is provided by the double deprotonation of nitroalkanes. In this case, the reaction with ketones affords P-nitro alcohols in 40-60% yield (Eq. 3.19).30... 

The nitro-aldol reaction using l,l-diethoxy-2-nitroethane is useful for lengthening of the carbon chain of carbohydrates. The reaction of Eq. 3.86 proceeds in a stereoselective way (ds 75%) to give the syw-nitro alcohol in 58% isolated yield.135 The product is converted into 2-amino-2-deoxyaldoses by reaction with H2/Raney Ni. 

Primary nitro compounds are good precursors for preparing nitriles and nitrile oxides (Eq. 6.31). The conversion of nitro compounds into nitrile oxides affords an important tool for the synthesis of complex natural products. Nitrile oxides are reactive 1,3-dipoles that form isoxazolines or isoxazoles by the reaction with alkenes or alky nes, respectively. The products are also important precursors for various substrates such as P-amino alcohols, P-hydroxy ketones, P-hydroxy nitriles, and P-hydroxy acids (Scheme 6.3). Many good reviews concerning nitrile oxides in organic synthesis exist some of them are listed here.50-56 Applications of organic synthesis using nitrile oxides are discussed in Section 8.2.2. 

Sequential Michael additions are versatile methods for the construction of cyclic compounds. Although a variety of these reactions have been developed, the use of alcohols as nucleophiles for the Michael addition to nitroalkenes has been little studied. Recently, Ikeda and coworkers have reported an elegant synthesis of octahydrobenzo[b]furans via the sequential Michael addition of 1-nitro-cyclohexene with methyl 4-hydroxy-2-butynoate in the presence of t-BuOK followed by radical denitration (Eq. 7.74).94... 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

Preparation of 2-dimethoxyphosphinyl-2-methoxy-2-phenylacetaldehyde oxime — Reaction of an unsaturated nitro compound with a trialkyl phosphite in the presence of an alcohol... 

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