Oxidative carbonylation of amines

Although many transition metals are known to promote oxidative carbonylation of amines to ureas, only palladium- and wolfram-catalyzed processes were used in the synthesis of compounds of pharmaceutical importance. Urea 46, a potent antagonist of the neuropeptide Y5 receptor was obtained starting from 9-isopropyl-4-methyl-9H-carbazol-3-ylamine and morpholine, using the Pdl2/KI catalyst under 20 bar of 4/1 carbon monoxide/air mixture [62], Intramolecular versions of this reaction were carried out vrith another system, using W(CO)6 as the catalyst and I2 as the oxidant during the synthesis of biotin methyl ester 47 [63], and the core structure of the HIV protease inhibitors 48 and 49 [64]. 

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The alkylurea 576 and oxamide 577 are formed by oxidative carbonylation of amines under CO pressure using Pd/C as a catalyst[518]. The urea formation proceeds under atmospheric pressure using PdCh and CuCl2[519]. The mono-and double carbonylations of / -aminoethanol (578 and 579) afford the cyclic carbamate (oxazolidinones) 580 and oxamide (morpholinediones) 581 [520,521]. 

Carbamates are produced by the oxidative carbonylation of amines in alcohol, and active research on the commercial production of carbamates as a precursor of isoyanates based on this reaction has been carried out. As an example, ethyl phenylcarbamate (582) is produced in a high yield (95%) with... 

Didgikar MR, Roy D, Gupta SP, Joshi SS, Chaudhari RV (2010) Immobilized palladium nanoparticles catalyzed oxidative carbonylation of amines. Ind Eng Chem Res 49 1027-1032... 

The oxidative carbonylation of amines to give ureas is at present one of the most attractive ways for synthesizing this very important class of carbonyl compounds via a phosgene-free approach. Ureas find extensive application as agrochemicals, dyes, antioxidants, resin precursors, synthetic intermediates (also for the production of carbamates and isocyanates), and HIV-inhibitors. Many transition metals (incuding Au [244], Co [248,253-255], Cu [242], Mn [249,256-258], Ni [259], Rh [246,247,260-262], Ru [224,260,263] and especially Pd [219,225,226,264-276], and, more recently, W [277-283]) as well as main-group elements (such as sulfur [284-286] and selenium [287— 292]) have been reported to promote the oxidative carbonylation of amines, usually under catalytic conditions. In some cases, carbamates and/or oxamides are formed as byproducts, thus lowering the selectivity of the process. 

The insertion of carbon monoxide was also the key step in the formation of urea derivatives through the oxidative carbonylation of amines. 6-Amino-... 

A few of these imply the carbonylation of nitroaromahc substrates [41], or the oxidative carbonylation of amines [42], or the reaction of amines with carbonic acid diesters [11] that are currently available, even on an industrial scale, through phosgene-free routes [43]. 

Gabriele B, Salerno G, Mancuso R et al (2004) Efficient synthesis of ureas by direct palladium-catalyzed oxidative carbonylation of amines. J Org Chem 69(14) 4741 1750... 

The oxidative carbonylation of amines to formamides was also reported in 2001 in up to 94% yield using Ph3PAuTCl as catalyst and oxygen as oxidant in methanol 7... 

Imidazolium alkylselenite ionic liquids were found to be efficient catalysts/solvents for the oxidative carbonylation of amines,1371 but in general the synthesis of carbonyl compounds is carried out in the presence of a palladium catalyst. The first example of such a transformation stems from... 

The oxidative carbonylation of amines has been performed using palladium complex catalysts. Rhodium and ruthenium complexes have also been sho vn to have catalytic activity in the preparation of carbamates and ureas [93, 94]. An example is sho vn in Eq. 11.47. The usual carbonylation of amines to give formamides vas discussed in Section 11.2.3. 

It is well known that the oxidative carbonylation of aniline and the reductive carbonylation of nitrocompounds to give DPU or MPC occur according to the stoichiometry of reactions (1-2) and (4-5). Alkoxycarbonyl complexes (M-COOR 1) and carbamoyl complexes (M-CONHR 2) which then evolve into the final products, are believed to be key intermediates for these reactions. The two accepted different mechanisms for the formation of 1 and 2 along with their catalytic cycles are illustrated in the schemes 1 and 2 for the oxidative carbonylation of amines catalyzed by noble metals. Both the cycles involve a two electron redox process. 

Carbamates and ureas are easily prepared and separated from the oxidative carbonylation of amines catalyzed by [PdCl2(phenanthroline)] dissolved in [G4GiIm]BF4. The carbonylation of terminal 3-alkyn-l-ols and l-alkyn-4-ols by palladium acetate/2-(diphenylphosphino)pyridine dissolved in [G4CiIm]PF6 or [C4CiIm]BF4 affords quantitatively and selectively v< -a-methylene (Scheme 21) and 7- and -lactones, respectively. ... 

Oxidative carbonylation of amines affords alkylurea469 and oxamide 470 [192]. Substituted ureas were prepared efficiently in the presence of Pdl2 and KI under CO and CO2 pressure (total 60 atm) [193]. Synthesis of 2-oxazolidinone (471) by the carbonylation of 2-aminoethanol was carried out efficiently using a catalytic system of Pdl2-KI [194]. 

Oxidative carbonylation of amines to carbamates and ureas in the presence of cobalt complexes was recently reported (24-25), We have found that Co(II) complexes bearing nitrogen and oxygen-donor ligands such as carboxylates, acetylacetonates and Schiff bases produce DMC with high selectivity in methanol under CO and Oj. (Table VII) (26-27),... 

Nitroaromatics have been reductively converted into aryl carbamate with methanol under CO atmosphere catalyzed by palladium(II) anchored onto montmorillonite clay. Conversely, the same carbamates can also be obtained via oxidative carbonylation of amines with carbon monoxide and oxygen in the presence of a bimetallic catalyst PdCl2-MnCl2 supported on poly( V-vinyl-2-pyrrolidone).f ... 

One such method (Scheme 4.3) involves the oxidative carbonylation of amines [235-238], or the catalytic production of carbamate esters by reductive carbonylation of nitro compounds [238-242], dealcoholysis of which gives isocyanates. 

Scheme 4.3. Oxidative carbonylation of amines [235-238] and reductive carbonylation of nitro compounds [238-242].

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 precise mechanism by which oxidative carbonylation of amines occurs is fer from being completely understood. However, some remarkable advances have been recently reported by Giannoccaro et al. [68-70] and Vasapollo et al. [71, 72], which are also relevant to the catalytic systems here described ... 

Overall, there is no evidence that any of the proposed steps is involved in the actual catalytic cycle. It should be noted that the feet that the same catalyst precursor also catalysed the oxidative carbonylation of amines [184, 185] raises the suspect that anilines may be intermediates in this reactions, analogously to what found for the other Ru-based systems previously discussed. 

The most promising approaches for the preparation of technologically important ureas and carbamates by nonphosgene routes are the catalytic oxidative carbonylation of amines in the presence of an alcohol or the reductive carbonylation of nitro... 

So that, the electrochemical methodology has permited a mild, selective and environmental friendly reoxidation of Pd(0) into Pd(II) in oxidative carbonylation of amines to ureas. The reaction was very selective (in most cases, no side product was formed) and good yields in ureas were obtained from aliphatic amines. 

Gabriele, B. Salerno, G. Mancuso, R. Costa, M. Efficient Synthesis of Ureas by Direct Palladium-Catalyzed Oxidative Carbonylation of Amines. J. Org.Chem. 2004, 69,4741 750. 

Catalytic Carbonylation with CO The oxidative carbonylation of amine to produce N-alkyl carbamate or N,N -disubstituted urea followed by thermal decomposition is a potential route for the non-phosgene synthesis of isocyanate. Scheme 2.23. 

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