Amines to carbamates

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... 

However, other catalyst systems with CuCl2 as cocatalysts [IbJ, which convert amines to carbamates at mild temperature conditions, have been also described. 

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),... 

Primary and secondary amines are also oxidized to aldehydes and ketones, via imines, using sulphonyl peroxides. The first reports of high-yield selective oxidative conversions of unbranched primary amines into em-dihalides (masked aldehydes) have appeared (Scheme 9), and the cleavage of tertiary amines to carbamates with ethyl chloroformate has been examined. ... 

Other new derivatization methods are also being developed [13,14]. For example, the use of alkylchloroformates as derivatizing agents allows conversion of certain amines to carbamates and carboxylic acids to esters. 

Scheme 1.10 Carboxy-alkylation of amines to carbamic esters.

Salt formation with Brmnsted and Lewis acids and exhaustive alkylation to form quaternary ammonium cations are part of the rich derivati2ation chemistry of these amines. Carbamates and thiocarbamates are formed with CO2 and CS2, respectively the former precipitate from neat amine as carbamate salts but are highly water soluble. 

Water and carbon dioxide from the atmosphere can be absorbed by the amines to form hydrates and carbamates, from primary and secondary amines, respectively. 

Na2C03, H2O, dioxane, warm, 97% yield. Phenols can be protected under similar conditions. Amines are converted by these conditions to carbamates... 

Na2C03, H2O, dioxane, warm, 97% yield. Phenols can be protected under similar conditions. Amines are converted by these conditions to carbamates that are stable to alkaline hydrolysis with sodium carbonate. Carbamates are cleaved by acidic hydrolysis (HBr, MeOH, CH2CI2, 8 h), conditions that do not cleave alkyl or aryl vinyl carbonates. 

When a carbonyl group is bonded to a substituent group that can potentially depart as a Lewis base, addition of a nucleophile to the carbonyl carbon leads to elimination and the regeneration of a carbon-oxygen double bond. Esters undergo hydrolysis with alkali hydroxides to form alkali metal salts of carboxylic acids and alcohols. Amides undergo hydrolysis with mineral acids to form carboxylic acids and amine salts. Carbamates undergo alkaline hydrolysis to form amines, carbon dioxide, and alcohols. 

In a variation of this reaction, alkyl halides can be converted to carbamates, by treatment with a secondary amine and K2CO3 under phase-transfer conditions. ... 

Oxidative carbonylation generates a number of important compounds and materials such as ureas, carbamates, 2-oxazolidinones, and aromatic polycarbonates. The [CuX(IPr)] complexes 38-X (X = Cl, Br, I) were tested as catalysts for the oxidative carbonylation of amino alcohols by Xia and co-workers [43]. Complex 38-1 is the first catalyst to selectively prepare ureas, carbamates, and 2-oxazolidinones without any additives. The important findings were the identity of the counterion and that the presence of the NHC ligand influenced the conversions. 2-Oxazohdinones were formed from primary amino alcohols in 86-96% yield. Complex 38-1 also catalysed the oxidative carbonylation of primary amines to ureas and carbamates. n-Propylamine, n-butylamine, and t-butylamine were transformed into the... 

Au Amines (oxidative carbonylation with CO/O2 to carbamates and symmetric ureas)... 

Direct oxidation of amides can also lead to Hofmann-type rearrangement with formation of amines or carbamates. One reagent that is used is Pb(02CCH3)4. 

Imidazole carboxylates of polyethylene glycols prepared with CDI react with amines to give polyethylene glycols (PEG) with carbamate end groups.12071 For example, PEG-... 

Gold(I) complexes of the type [AuCl(PPh3)ra] (n= 1, 2) or [Au(N03)(PPh3)] show an excellent performance towards oxidative addition carbonylation or aromatic amines to form corresponding carbamates, and also towards the carbonilation of aliphatic amines to produce either alkylureas or formamides.2552,2553 Cationic gold(I) compounds of the type [AuL]+ where L = phosphine, phosphite, or arsine are excellent catalysts for the addition of alcohols to alkynes.2554... 

CDI-activated hydroxyls also may undergo a side reaction to form active carbonates. This occurs when an imidazolyl carbamate reacts with another hydroxyl group before the second hydroxyl has had a chance to get activated with CDI. Particularly with adjacent hydroxyls on the same molecule, this can be a problem if a defined reactive species is desired. Any carbonates formed, however, are still reactive toward amines to create carbamate linkages. 

A recent study concerned the microwave-assisted parallel synthesis of di- and tri-substituted ureas utilizing dedicated 96-well plates in the CombiCHEM system [60], In a typical procedure, modification of the Marshall resin utilized was achieved by treatment with p-nitrophenyl chloroformate and N-methylmorpholine (NMM) in dichloromethane at low temperatures. The resulting resin was further modified by attaching various amines to obtain a set of polymer-bound carbamates (Scheme 7.48). 

The hydrogenation of C02 in the presence of amines to give dialkylformamides has been carried out directly in an IL/scC02 system. In this case, the ionic liquid was shown to play a dual role [74]. It is an effective solvent for the ruthenium phosphine catalyst and at the same time allows a distinct phase distribution of the polar carbamate intermediates and the less polar products formed during the conversion of C02. As a result, the selectivity of the reaction can be increased over conditions where scC02 is used as the sole reaction medium. 

Three alternative mechanisms have been mentioned in the literature. Reduction of C02 to CO followed by carbonylation of dimethylamine was ruled out by Haynes et al. [3] for RhCl(PPh3)3 because no carbonyl complexes were detected. Aminolysis of formate complexes (Eq. (14)) was proposed by Kudo et al. [69], but strong evidence has not been obtained. Finally, C02 is known to react with the amine to produce a carbamate salt (Eq. (15)), and it is possible that the pathway to the formamide is by hydrogenation of the carbamate rather than of the C02. 

Although dealkylation using haloformates has been used with tertiary amines to provide intermediate carbamates, in the case of aromatic amines the reaction requires a large excess of the chloroformate, high temperatures, and long reaction times. For example, see a) J. P. Bachelet, P. Caubere, 7. Org. Chem. 1982, 47, 234 b) R. A. Olofson, D. E. Abbott, 7. Org. Chem. 1984, 49, 2795 c) R. A. Olofson, Pure Appl. Chem. 1988, 60,1715. 

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. 

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. 

Transformation of amines to aldehydes or ketones can be carried out via the anodic a-methoxylation of the corresponding carbamates, (4), followed by an acid-catalyzed conversion of the a-methoxylated... 

For synthetic purposes the cyanate ion is a promising reagent leading to amines in water and to carbamates in dcohol (Hartsuiker et al., 1971). Alkyl-lithium reagents may also function in nucleophilic photosubstitutions with aromatic partners containing suitable leaving groups (Shapiro and Tomer, 1968). 

The scope of nitrolysis is huge, with examples of nitramine formation from the cleavage of tertiary amines, methylenediamines, carbamates, ureas, formamides, acetamides and other amides. The deflnition of nitrolysis must be extended to the nitrative cleavage of other nitrogen bonds because sulfonamides and nitrosamines are also important substrates for these reactions. The nitrative cleavage of silylamines and silylamides is also a form of nitrolysis (Section 5.7). 

The instability of primary nitramines in acidic solution means that the nitration of the parent amine with nitric acid or its mixtures is not a feasible route to these compounds. The hydrolysis of secondary nitramides is probably the single most important route to primary nitramines. Accordingly, primary nitramines are often prepared by an indirect four step route (1) acylation of a primary amine to an amide, (2) A-nitration to a secondary nitramide, (3) hydrolysis or ammonolysis with aqueous base and (4) subsequent acidification to release the free nitramine (Equation 5.17). Substrates used in these reactions include sulfonamides, carbamates (urethanes), ureas and carboxylic acid amides like acetamides and formamides etc. The nitration of amides and related compounds has been discussed in Section 5.5. 

---