Carbamic acid conversion

Conversion of the corresponding isocyanates, resulting from the heating of the azides in benzene, with alcohols of general formula R OH, yielded the carbamic acid esters LXXVIb (150), and with amines R"R" NH, the urea derivatives LXXVIc and LXXVIIc (151, 152). 

Scheme 1. SCCO2 as a protective medium changing chemoselectivity by in situ conversion of a secondary amine to its carbamic acid during catalysis in scCOa-...

Carbon dioxide reacts with primary amines to form a carbamic acid (Pine et al., 1980). Carbamic acids are unstable the very act of dissolving the carbamic acid in a solvent for titration or for conducting NMR studies, for example, converts the acid back to amine plus CO2 (Elsbernd, 1988). Heating the acid to about 50-100°C can force the reaction in the reverse direction, and if the CO2 that is generated is removed, the amine can be recovered. Although the conversion of carbamic acid back to amine plus CO2 occurs quite readily (Pine et al., 1980) the reversion is not instantaneous (Gallagher and Krukonis, 1987). What can also occur during the reverse reaction is reaction between any unconverted carbamic acid and the amine that has just reformed to form a urea. 

At 100 to 130°C, complete conversion of carbamic acid back to amine occurs within —20 min. 

Recently, the use of supercritical CO2 as a reaction medium was reported by Holmes and Smith [145], Here, the formation of carbamic acid from the corresponding amine with CO2 could be avoided by the use of silyl amines. With X-Phos as hgand and CS2CO3 as base, a range of couplings was accomplished, including the conversion of deactivated aryl chlorides, pyrroles, indoles and sulfonamides. 

Lewis acid Conversion % Yield of carbamate Yield of aniline Vo... 

Enzymatic Method. L-Amino acids can be produced by the enzymatic hydrolysis of chemically synthesized DL-amino acids or derivatives such as esters, hydantoins, carbamates, amides, and acylates (24). The enzyme which hydrolyzes the L-isomer specifically has been found in microbial sources. The resulting L-amino acid is isolated through routine chemical or physical processes. The D-isomer which remains unchanged is racemized chemically or enzymatically and the process is recycled. Conversely, enzymes which act specifically on D-isomers have been found. Thus various D-amino acids have been... 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

For conversion of amide to other acid derivatives, a novel synthesis of urea glycosides in aqueous media has been reported via the reaction of Steyermark s glucosyl carbamate with amines in good yields (Eq. 9.17).38 This method was successfully applied to develop a new route to the synthesis of urea-tethered neo-glycoconjugates and pseudooligosaccharides. 

The following reaction illustrates conversion of a nitroxide radical-bearing alcohol by CDI and azide ion to a spin-labeled ester of azido formic acid, which is used for the labeling of amino acids, giving carbamates [137]... 

Conversion to carbamates. Cyclic carbamates derived from sugars and related compounds have repeatedly been encountered, the first being an inosamine derivative, obtained by Curtius degradation of dihydroshikimic acid.82,83... 

Although there are other convenient procedures for the conversion of sulphides into sulphoxides and sulphones, the phase-transfer catalysed reaction using Oxone has the advantage that the oxidation can be conducted in the presence of other readily oxidized groups, such as amines, alkenes, and hydroxyl groups, and acid-labile groups, such as esters and carbamates [6, 7], Hydrolysis of very acid-labile groups, such as ketals, can result in production of the keto sulphone. 

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... 

In 2007, Tron and Zhu reported the multicomponent synthesis of 5-iminoox-azolines (42) starting from a,a-disubstituted secondary isocyano amides (41), amines, and carbonyl components (see Fig. 15) [155]. The reaction presumably follows a similar mechanism as in the 2,4,5-trisubstituted oxazole MCR (described in Fig. 11) however, because of the absence of a-protons at the isocyano amide 41, the nonaromatized product is obtained. As in the 2,4,5-trisubstituted oxazole MCR, toluene was found to be the optimal solvent in combination with a weak Brpnsted acid. The reaction was studied for a range of aldehydes and secondary amines. In addition, a variety of functionalities such as acetate, free hydroxyl group, carbamate, and esters are tolerated. Clean conversions were observed for this MCR as indicated by NMR analysis of the crude products (isolated yield 50-68%). The... 

Diones are normally synthesized from /3-hydroxy acids in two steps first, conversion into carbamates by reaction with sodium cyanate, and then cyclization with thionyl chloride (Scheme 103) (54JCS839). Alternative preparations utilize oxetanes, which may be combined either with isocyanates in the presence of boron trifluoride (68JAP6808278) or with S-alkylthioureas (Scheme 104) (69ZOR1844). In the last example the initial products are imines (224) which may readily be hydrolyzed to the required diones. Similar methods can be applied to the synthesis of tetrahydro-l,3-thiazine-2,4-diones, and, for instance, the 4-oxo-2-thioxo derivative (225) is obtained from /3-propiolactone and dithiocarbamic acid (Scheme 105) (48JA1001). 

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