Isocyanates nitro compounds

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]. 

Attempts have been made to develop methods for the production of aromatic isocyanates without the use of phosgene. None of these processes is currently in commercial use. Processes based on the reaction of carbon monoxide with aromatic nitro compounds have been examined extensively (23,27,76). The reductive carbonylation of 2,4-dinitrotoluene [121 -14-2] to toluene 2,4-diaLkylcarbamates is reported to occur in high yield at reaction temperatures of 140—180°C under 6900 kPa (1000 psi) of carbon monoxide. The resultant carbamate product distribution is noted to be a strong function of the alcohol used. Mitsui-Toatsu and Arco have disclosed a two-step reductive carbonylation process based on a cost effective selenium catalyst (22,23). 

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

In one projected commercial modification of the process the phosgenation stage is replaced by one in which the nitro compounds are reacted with CO and an alcohol to form a urethane. This is then split to form an isocyanate in the second step. 

Oxidation of Primary Amines, Oximes, Azides, Isocyanates, or Nitroso Compounds to Nitro Compounds... 

Dimethyl dioxirane in wet acetone oxidizes isocyanates to nitro compounds (RNCO —> RN02). Oximes can be oxidized to nitro compounds with peroxytri-fluoroacetic acid, or Oxone ," sodiumperborate," among other ways. " Primary and secondary alkyl azides have been converted to nitro compounds by treatment with PhjP followed by ozone. Aromatic nitroso compounds are easily oxidized to nitro compounds by many oxidizing agents. ... 

Isocyanates and isothiocyanates are reduced to methylamines on treatment with LiAlH4. Lithium aluminium hydride does not usually reduce azo compounds (indeed these are the products from LiAlH4 reduction of nitro compounds, 19-59), but these can be reduced to hydrazo compounds by catalytic hydrogenation or with... 

The standard reaction sequence for transformation of a carboxylic acid into a nitro group is lengthy. Eaton has shortened this conversion via oxidation of isocyanates to nitro compounds with dimethyldioxirane in wet acetone (Eq. 2.71).140... 

Reductive carbonylation of nitro compounds (in particular aromatic dinitro compounds) is an important target in industry for making diisocyanates, one of the starting materials for polycarbamates. At present diisocyanates are made from diamines and phosgene. Direct synthesis of isocyanates from nitro compounds would avoid the reduction of nitro compounds to anilines, the... 

Nitrenes can be generated from many precursors such as azides, isocyanates, ylides, heterocycles, and nitro compounds.236,237 Amongst these, azides are the most convenient precursors since they are easily prepared and can be decomposed by heat, light or a suitable catalyst. Despite considerable endeavors, no one has yet provided a synthetically viable method to use azides as sources of nitrenes.237 The breakthrough of nitrene chemistry was the recognization of the value of A-arenesulfonyl iminoiodinanes (ArS02N=IPh) as nitrene precursors by Breslow and Mansuy. - They reported inter- and intramolecular C-H insertions by tosylimino phenyl-iodinane (TsN=IPh) in the presence of Mn(m) or Fe(m) porphyrins or [Rh2(OAc)4]. Subsequently, Muller... 

Sodium perborate in acetic acid converts oximes into nitro compounds thus acetophenone oxime yields 52% of PhCHMeN02403. Nitroalkanes and nitroarenes are obtained from isocyanates and dimethyldioxirane (equation 122)404. 

The nitration of aromatic hydrocarbons is one of the most widely studied and well-documented reactions in organic chemistry. Aromatic nitro compounds are of huge industrial importance in the synthesis of pharmaceutical drugs, agrochemicals, polymers, solvents and perfumes, and for the synthesis of other industrially important chemicals containing amine and isocyanate functionality. However, early research into aromatic nitration was fuelled exclusively by their use as explosives and intermediates in the synthesis of dyestuffs. The former is the subject of this chapter. 

An intramolecular cycloaddition of the tetradecatrienyl nitroethyl ether 263 was used in the synthesis of the 14-membered bicyclic precursor 265 of crassin acetate 266, a cembrane lactone possessing antibiotic and antineoplastic activity (332). Nitro compound 263 was obtained from farnesyl acetate (262) in several steps and was then treated with phenyl isocyanate and triethylamine to give the tricyclic isoxazoline 264 (Scheme 6.98). Conversion to ketone 265 was accomplished by hydrogenation of the cycloadduct with Raney Ni and boric acid followed by acetylation (332). In this case, the isoxazoline derived from a 3-butenyl nitroethyl ether moiety served to produce a 3-methylenetetrahydropyran moiety (332). 

One of the very first uses of the intramolecular nitrile oxide cycloaddition involved the synthesis of macrocyclic lactones. Asaoka et al. (238) conceived this approach to the 16-membered ring antibiotic A26771B (277). Nitro compound 274 [obtained from 11-acetoxydodecanal (273)] was dehydrated with 4-chlorophenyl isocyanate-triethylamine and this was followed by dipolar cycloaddition, which gave isoxazoline 275 as a 4 1 mixture of diastereomers (Scheme 6.100). 

Oxidative cleavage of amines 9-39 Reduction of amides 9-47 Reduction of nitro compounds 9-50 Reduction of nitroso compounds or hydroxylamincs 9-51 Reduction of oximes 9-52 Reduction of azides 9-53 Reduction of isocyanates, isothiocyanates, or N-nitroso compounds 9-55 Reduction of amine oxides 9-59 Reduction of azo, azoxy, or hydrazo compounds... 

Nitrile oxide J -I- 2 cycloaddition.1 A key step in a recent stereospecific synthesis of biotin (6) from cycloheptene (1) is an intramolecular [3 + 2]cyclo-addition of a nitrile oxide (a), obtained by dehydration of a primary nitro compound (3), preferably with phenyl isocyanate. This cycloaddilion is more efficient than the well-known olefinic nitrone cycloaddition. The carbon atoms in 6 derived from cycloheptene are marked with asterisks. 

Quite independently of Cornforth s efforts, a similar approach was designed and executed by Stevens and coworkers (75JA5940, 76T1599). The isoxazoles were synthesized by one of the three routes outlined in Scheme 25, in which primary nitro compounds are transformed into nitrile oxides by dehydration with either phosphoryl chloride or phenyl isocyanate, or else the same oxides were formed by dehydrogenation with LTA (syn product) or NBS (syn and anti). Reaction of the unstable nitrile oxides in situ with an appropriately substituted alkyne then afforded the isoxazole (294). 

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