Carbamates from nitro compounds

A fourth type of product, a carbamate RNHCOOR , can be obtained from primary or secondary amines, if these are treated with CO, O2, and an alcohol R OH in the presence of a catalyst. " Primary amines react with dimethyl carbonate in supercritical CO2 (see p. 414) to give a carbamate. " Carbamates can also be obtained from nitroso compounds, by treatment with CO, R OH, Pd(OAc)2, and Cu(OAc)2, " and from nitro compounds. " When allylic amines (R2C=CHRCHRNR 2) are treated with CO and a palladium-phosphine catalyst, the CO inserts to produce the p,y-unsa-turated amides (R2C=CHRCHRCONR 2) in good yields. " Ring-expanded lactams are obtained from cyclic amines via a similar reaction (see also, 16-22). Silyloxy carbamates (RNHC02SiR 3) can be prepared by the reaction of a primary amine with carbon dioxide and triethylamine, followed by reaction with triisopropylsilyl triflate and tetrabutylammonium fluoride. ... 

The application of carbon monoxide as a reductant in organic synthesis is confined to relatively few examples. In the last 25 years, the catalytic reductive carbonylation of organic nitro compounds has become a very intense field of research. This is because a series of industrially important compounds can be obtained from nitro compounds and carbon monoxide in a single step. Very important chemicals such as isocyanates (Eq. 1), carbamates (Eq. 2) and ureas (Eq. 3) can be obtained by this methodology ... 

Carbamates can be obtained from primary or secondary amines by treating these with CO, O2, and an alcohol in the presence of a catalyst [592, 593]. Carbamates can also be obtained from nitroso compounds by treatment with CO, ROH, Pd(OAc)2, and Cu(OAc)2 [594] and from nitro compounds [595, 596]. 

In the previous paragraph, we have already mentioned a [Rh(CO)2Cl]2-based catalytic system for the synthesis of carbamates [160]. The use of simple RhCL as catalyst precursor for the synthesis of ureas from nitro compounds and anilines has also been reported [163]. A 77 % yield of diphenylurea from nitrobenzene and aniline was reported, but conditions were quite forcing (190 °C, 205 Kg/cm CO, for 2 h). 

Very little has been done on the use of iron compounds in the synthesis of carbamates and ureas from nitro compounds. It has long been known [191] that heating aliphatic nitro compounds with an excess of Fe(CO)s (1.4 mol for 1.0 mol of nitro compound) in diglyme at 120-132 °C for 15-17 h affords low yields of formamides and ureas, but the yield of urea is at best 18.5 % (in the case of nitrocyclohexane yields were even lower for 1- or 2-nitropropane, 2-methyl-2-nitropropane, and 1-nitroadamantane). These experiments were among the first... 

The direct catalytic synthesis of azo or azoxy compounds from nitro compounds is not a common reaction. Apart from Fe(CO)5, Ru3(CO)i2 has been reported to catalyse reaction 17 [113], but mononitro compounds failed to give appreciable amounts of azo compounds with this catalyst. Very recently, however, it has been reported that good selectivities (up to 72.5 %) in azoxybenzene can be obtained by using Pd(Phen)(OTf)2 as catalyst in the presence of an excess (best 12.5 1 with respect to palladium) of sodium benzoate [114]. Conditions were 60 bar and 135 °C in methanol as solvent (note that no water was added). The principal by-product was methyl phenylurethane, with minor amounts of aniline and diphenylurea being also formed. The study was principally aimed at evidencing the effect of benzoate anion on the synthesis of carbamates, so no attempt has apparently been made to optimise the experimental conditions for the synthesis of azoxybenzene and better yields can be probably obtained under different conditions. 

Kim JG, Jang DO (2009) Indium-catalyzed reaction for the synthesis of caibamates and carbonates selective protection of amino groups. Tetrahedron Lett 50(22) 2688-2692 Paul F (2000) Catalytic synthesis of isocyanates or carbamates from nitroaromatics using group viii transition metal catalysts. Coord Chem Rev 203(l) 269-323 Dieck HA, Laine RM, Heck RE (1975) Low-pressure, palladium-catalyzed iV4V -diarylurea synthesis from nitro compounds, amines, and carbon monoxide. J Org Chem 40(19) 2819-2822... 

The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate salts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pKg value of the base to ensure almost complete formation of the cation. They are extracted with diethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines (isocyanides) are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

By carbonyl ation of DNT in ethanol with Se and KOAc as catalyst, the dicarbamate was obtained in 83% yield (100-200 C, 10-200 atm)[299]J, Sulphur was also used as catalyst. Carbamates have been obtained from aromatic nitro compounds, CO, alcohols and a catalyst which is a metal selenide together with an (in)organic base or iodide [300j. 

Carbonic add diesters are very attractive reagents and of great economic interest because they represent safe, nonenvironmentally acceptable alternatives to phosgene for carbonylation and carboxylation reactions. For example, methoxycarboxylation with dimethyl carbonate offers an eco-friendly alternative route for the production of carbamates and isocyanates, which are valuable precursors of ureas (see Sections 4.3.1 and 4.3.2) [781, 782]. The method is comparable, from an environmental point of view, with the transition metal catalyzed carbonylation of nitro compounds and amines with CO. 

Anilines are virtually always present as by-products, however, in some cases, they are also intermediates in the synthesis of carbamates and ureas. This last possibility will be discussed in more detail for the individual catalytic systems. When the aniline is a by-product, the necessary hydrogen atoms can originate from small amounts of water or H2 present as impurities in the solvent and/or the CO gas, but can also be produced by alcohol dehydrogenation (when an alcohol is present) or, to a minor extent, by direct hydrogen-atom abstraction from the solvent or from the nitro compound itself. Among primary alcohols, methanol is the less prone to be dehydrogenated [8]. 

More mechanistically important information contained in the patents from Grate et al. include the fact that addition of an amine corresponding to the nitro compound to the catalytic system accelerates the reaction, but the amine in not in the net consumed. If an amine not corresponding to the starting nitro compound is used, mixtures of carbamates are obtained. 

Addition of aniline to the catalytic system improves the conversion and the selectivity [189]. The added aniline is not in net consumed. If an aniline bearing different substituents from the nitro compound is used, mixtures of carbamates and anilines are formed [1]. 

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