Carbonylation of Alcohols and Amines

4 Carbonylation of Alcohols and Amines- Decompoation of fonnams by Ro3(00)i2 synthesis gas provides a convenient route to AiNHCOR via ArN02 reduction and subsequent carbonylation of the anilides formed in These reactions which proceed only at high 

This type of carbonylation reactions may lead to a great variety of products, such as carboxylicadds, esters, ureas, lactams, and so on, depending on the reaction conditions. 

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Many different substrates can undergo oxidative carbonylations, such as unsaturated and saturated hydrocarbons, aromatic and heteroaromatic derivatives, alcohols, phenols, and amines, giving a number of carbonyl compounds in a regio- and stereocontrolled fashion and with high degree of chemoselectivity. Oxidative car-bonylation reactions have been recently and carefully reviewed [10-13]. In this section a general overview of the most recent developments in oxidative carbonylations mediated by catalytic palladium(II) compounds and directed toward the synthesis of heterocyclic compounds is presented. As already reported in the introduction, the cyclocarbonylation reactions ending with the synthesis of simple lactones and lactams are reported in the chapter that discusses the carbonylation of alcohols and amines and are recently been reviewed [7,9,79]. 

Oxidative carbonylation is not necessarily associated with C - C bond formation. Indeed, heteroatom carbonylation may occur exclusively, as in the oxidative carbonylation of alcohols or phenols to carbonates, of alcohols and amines to carbamates, of aminoalcohols to cyclic carbamates, and of amines to ureas. All these reactions are of particular significance, in view of the possibility to prepare these very important classes of carbonyl compounds through a phosgene-free approach. These carbonylations are usually carried out in the presence of an appropriate oxidant under catalytic conditions (Eqs. 31-33), and in some cases can be promoted not only by transition metals but also by... 

The direct conversion of alcohols and amines into carbamate esters by oxidative carbonylation is also an attractive process from an industrial point of view, since carbamates are useful intermediates for the production of polyurethanes. Many efforts have, therefore, been devoted to the development of efficient catalysts able to operate under relatively mild conditions. The reaction, when applied to amino alcohols, allows a convenient synthesis of cyclic urethanes. Several transition metal complexes, based on Pd [218— 239], Cu [240-242], Au [243,244], Os [245], Rh [237,238,246,247], Co [248], Mn [249], Ru [224,250-252], Pt [238] are able to promote the process. The formation of ureas, oxamates, or oxamides as byproducts can in some cases lower the selectivity towards carbamates. 

Reductive -elimination of A3-iodanes on carbon atoms (M = C) produces C-C double bonds, while that on oxygen and nitrogen atoms (M = O and N), combined with the initial ligand exchange reaction, provides a method for oxidation of alcohols and amines to the corresponding carbonyl compounds and imines, respectively [Eq. (26)]. 

The Infrared Region 515 12-4 Molecular Vibrations 516 12-5 IR-Active and IR-lnactive Vibrations 518 12-6 Measurement of the IR Spectrum 519 12-7 Infrared Spectroscopy of Hydrocarbons 522 12-8 Characteristic Absorptions of Alcohols and Amines 527 12-9 Characteristic Absorptions of Carbonyl Compounds 528 12-10 Characteristic Absorptions of C—N Bonds 533 12-11 Simplified Summary of IR Stretching Frequencies 535 12-12 Reading and Interpreting IR Spectra (Solved Problems) 537 12-13 Introduction to Mass Spectrometry 541 12-14 Determination of the Molecular Formula by Mass Spectrometry 545... 

Additional reactions which need to be highlighted are the reductive alkylation of alcohols and amines with aldehydes leading to the green synthesis of ethers and amines. These reactions are generally catalyzed by palladium [35]. This reaction can replace the classical Williamson s synthesis of ethers which requires an alcohol and an alkyl halide together with a base, and always results in the concomitant production of salt. The choice of Pd/C as catalyst is due to the low efficiency of this metal for the competitive carbonyl reduction. Analysis of the... 

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]. 

Quinoproteins constitute a class of dehydrogenases distinct from the nicotinamide-and flavin-dependent oxidoreductases 11691. They use different quinone cofactors to convert a vast variety of alcohols and amines into their corresponding carbonyl products11701. Proteins containing the cofactor pyrroloquinoline quinone (PQQ) (Fig. 16.2-36) form the largest and best-characterized sub-group. 

By 1974 the latter reaction had been generalized, and a wide variety of organic halides and other related electrophiles including alkenyl and aryl halides had been used, most notably by Heck and co-workers. Also developed in his study was a related carbonylation reaction for the synthesis of amides. Use of organometals and metal hydrides in place of alcohols and amines most notably by Steffy and Stille further expanded the scope of Pd-catalyzed carbonylation. 

Biomimetic oxidations of alcohols and amines to carbonyl compounds continue to attract attention. Whilst methods are not yet of significant synthetic value, advances have been made in the development of oxidation catalysts. The isoalloxazine (1), when complexed with zirconium(iv), acts as an efficient catalyst for the oxidation of alcohols by oxygen, and the pyrimidopteridines (2) show high autorecycling efficiency in the oxidation of cyclopentanol. The deazatoxoflavin derivatives (3) oxidize primary amines to imines with high turnover of the catalyst. Subsequent hydrolysis liberates the carbonyl compound. 

Unsymmetric anhydrides that react selectively on one side are useful. Although formic anhydride is unstable above 10°C, acetic formic anhydride can be prepared by stirring sodium formate with acetyl chloride in ether (64% yield, bp 27-28°C) [22]. It is useful for the formylation of alcohols and amines. A stable solid formylating agent is the mixed anhydride prepared in 89% yield from p-methoxybenzoyl chloride and sodium formate catalyzed by a polymeric pyridine oxide [23]. Ethyl chlorofor-mate gives mixed anhydrides with various carboxylic acids which are then susceptible to nucleophilic substitution at the carboxylic carbonyl carbon. 

Alcohols are weak acids, 16-18, but their conjugate bases form easily. We have seen that the reaction of alkoxides as nucleophiles is an important feature of the chemistry of alcohols. In contrast, amines are very weak acids, pA 35. The difference in acidities of alcohols and amines agrees with the periodic trends for CH4NH2 and H2O. Because amines are very weak acids, the chemistry of their conjugate bases is quite limited. In fact, the conjugate bases of amines such as hthium diisopropyl-amide are used only to form conjugate bases of compounds such as enolates of carbonyl compounds. 

The Shvo catalyst 1 can participate in the transfer of hydrogen from one molecule to another. Such hydrogen transfer reactions are useful in synthetic organic chemistry for the reduction of ketones (aldehydes) and imines, and for the oxidation of alcohols and amines. In the former case (transfer hydrogenation), a hydrogen donor such as isopropanol or formic acid is used, which reduces the carbonyl compound or imine to alcohol or amine, respectively. In the oxidation of alcohols and amines (transfer dehydrogenation), a hydrogen acceptor such as acetone or a quinone is used. 

BINAP (40a) was first reported as a ligand in an enantioselective hydrogenation in 1980 [172], and provides good selectivity for the reductions of dehydroamino acid derivatives [173], enamides, allylic alcohols and amines, and a,p-unsaturated acids [4, 9, 11, 12, 174, 175]. The fame of the ligand system really came with the reduction of carbonyl groups with ruthenium as the metal [11, 176]. The Rh-BINAP systems is best known for the enantioselective isomerizations... 

Under appropriate conditions, alcohols and amines can undergo an oxidative double carbonylation process, with formation of oxalate esters (Eq. 34), oxamate esters (Eq. 35) or oxamides (Eq. 36). These reactions are usually catalyzed by Pd(II) species and take place trough the intermediate formation of bis(alkoxycarbonyl)palladium, (alkoxycarbonyl)(carbamoyl)palladium or bis(carbamoyl)palladium complexes, as shown in Scheme 29 (NuH, Nu H = alcohol or amine) [227,231,267,293-300]. 

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