Nitroarenes reductive carbonylation

The reductive carbonylation of nitroarenes with transition metal catalysts is a very important process in industry, as the development of a phosgene-free method for preparing isocyanate is required. Ruthenium, rhodium, and palladium complex catalysts have all been well studied, and ruthenium catalysts have been shown to be both highly active and attractive. The reduction of nitroarene with CO in the presence of alcohol and amine gives urethanes and ureas [95], respectively, both of which can be easily converted into isocyanates [3,96]. 

Ureas. Nitroarenes undergo reductive carbonylation and the in situ trapping with unhindered secondary amines leads to unsymmetrical ureas. 

Reductions of aromatic nitro compounds provide a simple and general access to various heterocyclic compounds through the domino process (Scheme 9.23). Quinolines are important skeletal moieties present in various natural products and biologically active compounds [58]. Most common methods of their preparation involve condensation of o-amino benzaldehydes with an enolizable carbonyl compound (Friedlander synthesis) [59]. Miller et al. [60] reported an efficient synthesis of quinolines 109, in which a reduction of o-nitroaryl carbaldehyde by SnCl2 followed by condensation with an enolizable carbonyl compound in the presence of ZnCl2 yielded 109 through a domino process. In 2001, Bunce et al. [61] reported a domino nitroarene reduction/reductive amination sequence for the preparation of tetrahydroquinoline-4-carboxylic ester 110 with excellent yields. 

NiHMA TPD Presence of Lewis sites determined Acid catalyst chemo-and regioselective reduction of nitroarenes and carbonyl compounds (311)... 

The chemistry involved in several selenium-based processes have been partly reviewed [218], but this review does not deal in detail with reductive carbonylation of nitroarenes. A more specific review on the use of selenium in... 

The reaction described in eq. 8 is promoted by bases, with tertiary amines being often used [220]. Since some base is always added in all catalytic reactions, it has also been suggested that H2Se is in equilibrium with the deprotonated forms HSe and Se and that these last species may be the ones responsible for nitroarene reduction [213], Since no mechanistic study has been conducted on the selenium-catalysed reductive carbonylation of nitroarenes, we will not discuss the details of the mechanistic pathway. However, the occurrence of the reactions described by eqs. 7-10 appears to be well based. The reduction of nitroarenes by CO/H2O (see Chapter 4) and the oxidative carbonylation of amines by CO/O2 [218] have both been reported to be catalysed by selenium under conditions similar to those employed in the reactions here discussed. 

The use of sulphur or sulphur compounds, even in the presence of a metal compound (most often vanadium), as a catalyst for the reductive carbonylation of nitroarenes have also attracted some attention [222-235]. Sulphur compounds are isoelectronic to their selenium analogues and some similarities in the reactivity of COS and H2S with respect to SeCO and H2Se is to be expected. Sulphur has the very important advantage of having a much lower toxicity than selenium, but the reactivity of its compounds is also much lower. As a consequence, several of the processes reported employ a stoichiometric amount of sulphur or, in the catalytic processes, the catalytic efficiency is extremely poor. Catalytic ratios around 2-4 are conunon and this number is never higher than 10. This implies than a very large amount of sulphur is always necessary and needs to be separated from the products and recycled. The form in which sulphur is present at the end of the process has never been reported. If oxygenated products are formed at least in part, as it is likely, their elimination may be costly or environmentally problematic. 

Evidence for the intermediate formation of nitrone species during the carbonylation of nitroarenes in e s-cyclooctene as solvent catalysed by Ru3(CO)i2 have been obtained [14], Moreover, zerovalent palladium species with nitrogen donor ligands have been shown to be active catalysts in the reductive carbonylation of organic nitro derivatives [41]. The hypothesis that an intermediate having the olefinic double bond coordinated to the metal is formed during the catalytic cycle is supported by the steric effect that has been observed in the case of p,p -dimethyl-o-nitrostyrene (7f) as substrate. Moreover, such an intermediate could explain why a pentaatomic indole nucleus is preferentially formed, even when a conjugated double bond is present in the olefinic chain ... 

During the reductive carbonylation of nitroarenes to carbamates catalysed by PdCb-Lewis acids, the nitroarene is first reduced to the corresponding aniline that is then carbonylated. Depending upon the conditions, more amine may be consumed than nitro compound. 

As discussed in Chapter 9, various nucleophiles can be introduced at the ortho position of nitroarenes via the VNS process. This provides a useful strategy for the synthesis of indoles. One of the most attractive and general methods of indoles and indolinones would be the reductive cyclization of a-nitroaryl carbonyl compounds (Eq. 10.54). The VNS and related reactions afford a-nitroaryl carbonyl compounds by a simple procedure. For example, alkylation of 4-fluoronitrobenzene with a lactone silyl enol ether followed by reductive cyclization leads to tryptophols (Eq. 10.55).73... 

Nitroarenes are reduced to anilines (>85%) under the influence of metal carbonyl complexes. In a two-phase system, the complex hydridoiron complex [HFe,(CO)u]2-is produced from tri-iron dodecacarbonyl at the interface between the organic phase and the basic aqueous phase [7], The generation of the active hydridoiron complex is catalysed by a range of quaternary ammonium salts and an analogous hydrido-manganese complex is obtained from dimanganese decacarbonyl under similar conditions [8], Virtually no reduction occurs in the absence of the quaternary ammonium salt, and the reduction is also suppressed by the presence of carbon monoxide [9], In contrast, dicobalt octacarbonyl reacts with quaternary ammonium fluorides to form complexes which do not reduce nitroarenes. 

In many respects the apparently analogous reduction of nitroarenes with triruthenium dodecacarbonyl under basic phase-transfer conditions is superior to that of the iron carbonyl-mediated reductions. However, the difference in the dependence of the two processes on the concentration of the aqueous sodium hydroxide and the pressure of the carbon monoxide suggests that they may proceed by different mechanisms. Although the iron-based system is most effective under dilute alkaline conditions in the absence of carbon monoxide, the use of 5M sodium hydroxide is critical for the ruthenium-based system, which also requires an atmosphere of carbon monoxide [11]. The ruthenium-based reduction has been extended to the... 

The mechanism and rate of reduction of nitroarenes by cluster rhodium/cobalt carbonyls under basic conditions and catalysed by dodecyltrimethylammonium chloride has been reported [13]. 

Grignard additions, 9, 59, 9, 64 indium-mediated allylation, 9, 687 in nickel complexes, 8, 150 ruthenium carbonyl reactions, 7, 142 ruthenium half-sandwiches, 6, 478 and selenium electrophiles, 9, W11 4( > 2 in vanadocene reactions, 5, 39 Nitrites, with trinuclear Os clusters, 6, 733 Nitroalkenes, Grignard additions, 9, 59-60 Nitroarenes, and Grignard reactivity, 9, 70 Nitrobenzenes, reductive aminocarbonylation, 11, 543... 

Catalytic reduction in methanol using decaborane as the hydrogen source successfully saturates alkenes and alkynes and converts nitroarenes to arylamines. Concurrent A -alkylation to afford ArNHCHRR occurs when a carbonyl compound (RR C=0) is present. " ... 

Metal carbonyl reactions. The first examples of phase-transfer catalysis in a metal carbonyl reaction were reported in 1977. Thus the reduction of nitroarenes by FesfCOfia (5, 534) can be conducted under phase-transfer conditions in yields comparable to, or even superior to, those obtained under classical conditions (equation I). The actual reducing agent is believed to be sodium hydridoundeca-... 

Coupling reactions using orf/zo-haloanilines have been widely used in these instances no reductive step is required, though the carbonyl unit is sometimes incorporated in masked form requiring deprotection the examples shown are a palladium-catalysed coupling and a silyl ether/nitroarene condensation. ... 

Ruthenium catalysts was explored and applied in the reduction of nitro compounds as well. But because of its high price, their large scale applications are limited. Cenini and colleagues reported a Ru3(CO)i2 and Ru(CO)3(PPh3>2 catalyzed carbonylation of nitroarenes [44, 45]. The corresponding carbamates are produced in high selectivity in the presence of NEt4Cl under 82 bar of CO. 

Iron-substituted mesoporous aluminophosphate was used as a novel, efficient and ecofriendly catalyst for reductive cleavage of azo dyes and reduction in nitroarenes and catalytic transfer hydrogenation of nitro and carbonyl compounds. Unlike most of the iron-containing molecular sieves, dislodgement of tetrahedral Fe(III) was not observed upon various process treatments such... 

A number of studies of the important (non-phosgene) route to aryl isocyanates via carbonylation of nitro compounds have appeared. In a comparative study of Rh(I), Ir(I), Pd(I) and Pd(II) catalysts, Bu,N+[RhX2(CO)2] (X Cl, Br, I) was most effective giving 83-89% PhNCO with 100% PhN02 conversion at 125 C under 80 atm CO pressure . The kinetics of carbonylation by [PdCl2py2l at 170-230 C and 23-94 atm CO pressure are first order in p[CO] and catalyst and zero order in PhNOj . The reductive N-carbonylation of nitroarenes to the carbamates is catalysed by tPtCl2 (PPh3 >2] in ethanol, promoted by Lewis acids (SnCli,... 

The formation of metal-oxo species which are not reduced by CO under the reaction conditions, or are only very slowly so, probably accounts for the fact that these reductions are not catalytic in the metal. In our experience [74], several molybdenum, vanadium and rhenium complexes that may act through a sequence of reactions like the one in eqs. 22 and 23, gave only negative results when used as catalysts in carbonylation reactions of nitroarenes. It appears that reaction 22 is fest in many cases, but reaction 23 is very slow, even when thermodynamically favourable, and its rate is too low to allow for an efficient catalytic cycle even at high temperature and under CO pressure. 

For M = Ru, formamides and amines were the principal products. Substitution of Fe3(CO)i2 for Ru3(CO)i2 results in the formation of carbamate esters (ArNHCOOMe) as the major products, with ureas as the main by-products. Without the metal carbonyl, nitroarenes are recovered imchanged from the reaction mixture. An imido-alcoxycarbonyl complex was suggested as an intermediate in the reaction and the difference between iron and ruthenium was proposed to be due to the different facility of this intermediate to undergo protonation and reductive elimination to give carbamate, or insertion of CO into the M-N bond, followed by hydrogenation, affording formamide (Scheme 13) ... 

Azo- and azoxyarenes are often found as by-products in reduction and carbonylation reactions of nitroarenes. It has been shown in several cases (see Chapter 3) that both of these two products can be further reduced and/or carbonylated by the same catalytic systems that reduce and carbonylate nitroarenes, to afford the same products. However, though the reduction from azoxy- to azoarene may be fast under certain conditions, the further reactions of azoarenes are very slow compared to the global reaction when the corresponding nitroarenes are used as substrates, indicating that, unlike nitrosoarenes, azo- and azoxyarenes cannot be intermediates in the main catalytic pathway. In at least... 

Following the isolation of these complexes, all of the mechanistic studies on the carbonylation and reduction reactions of nitroarenes catalysed by Ru3(CO)i2, even in the presence of several promoters, have focused on the reactivity of these or related clusters [157-164]. Moreover, many studies have been also conducted on analogous osmium [165-172] and iron (see paragraph 6.6.) clusters, including insertion reactions of isocyanates, which yield potential intermediates in the carbonylation reaction (Insertion reaction of other cumulenes into the Ru-N bond will not be discussed here. However, see the paragraph of the synthesis of heterocycles later in this chapter). Although not all of the previously mentioned studies were intended to be a basis for a mechanistic understanding of the reactions here discussed, they still contain a lot of information on the possible transformations of amido or imido moieties on a trinuclear cluster. 

In this paragraph, we will discuss catalytic systems in which an iron compound is the only catalyst, that is we will not consider those systems in which an iron compound is used as a cocatalyst in what is considered to be a palladium- or rhodium-based eatalytic system. These last systems have already been discussed in paragraphs 6.3.1. and 6.5.2. Synthetic applications of iron-based systems for the carbonylation (Chapter 3) and reduction (Chapter 4) of nitroarenes have already been described. 

Reductions of aldehydes and ketones to alcohols proceed at slower rates with AERs in BH4 form than with NaBH4 in ethanol.a,j8-Unsaturated carbonyl compounds are reduced by BH4 in a gel AER to the allylic alcohols. Cyanoborohydride ion in a macroporous AER effects reductive aminations of ketones and ammonia to primary amines, reductive methylations of primary amines to the N,iV-dimethyl tertiary amines with aqueous formaldehyde, reductions of N-alkyl- and AT-acyl-pyridinium ions to tetrahydropyridines, and reductions of primary alkyl halides to alkanes. Nitroarenes are reduced to amines, the bromide of a-bromocarbonyl compounds is replaced by hydride, and 1,2-dibromoalkanes give alkenes by treatment with HFe(CO)4 in a macroporous AER. 

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