Reduction of carbamates

Bourbon Distillation. The basic distiUation system for the production of bourbon and other straight whiskeys consists of a beer stiU and a beer heater, thumper, or doubler (Fig. 4). The whiskey stiU consists of between 14 and 21 stripping trays. The upper portion of the stiU is fitted with either a bubble cap section or a section packed with copper rings to enhance the removal of unwanted flavors and ethyl carbamate precursors. The reduction of carbamate precursors requites strict adherence to a cleaning protocol with a 5% caustic solution as often as twice a week. 

In the last steps, all that remained was to reduce the azide and methylate the resulting amine. Reduction of azide was cleanly effected by hydrogen over Pd/C. The problem of selectivity in reduction of carbamate to Me group was circumvented, however, by using LiAlH(OMe3) in refluxing THE. 

Because an excess of ammonia is fed to the reactor, and because the reactions ate reversible, ammonia and carbon dioxide exit the reactor along with the carbamate and urea. Several process variations have been developed to deal with the efficiency of the conversion and with serious corrosion problems. The three main types of ammonia handling ate once through, partial recycle, and total recycle. Urea plants having capacity up to 1800 t/d ate available. Most advances have dealt with reduction of energy requirements in the total recycle process. The economics of urea production ate most strongly influenced by the cost of the taw material ammonia. When the ammonia cost is representative of production cost in a new plant it can amount to more than 50% of urea cost. 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Carbonates, like esters, can be cleaved by basic hydrolysis, but generally are much less susceptible to hydrolysis because of the resonance effect of the second oxygen. In general, carbonates are cleaved by taking advantage of the properties of the second alkyl substituent (e.g., zinc reduction of the 2,2,2-trichloroethyl carbonate). The reagents used to introduce the carbonate onto alcohols react readily with amines as well. As expected, basic hydrolysis of the resulting carbamate is considerably more difficult than basic hydrolysis of a carbonate. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

This ring system could be prepared by building either of the two heterocycles and then doing an annulation. Thus, cyclization of ethyl o-nitrophenylhydrazonocyanoacetyl carbamate 552 afforded 553. Reduction of 553 by the action of iron(II) sulfate gave 554, which on acid hydrolysis gave 558. Cyclization of o-aminophenyl derivatives 554 and 558 to 555 and 559, respectively, was effected (77CCC894) by treatment with acid. Phthalimido derivatives of 554 could also be cyclized to this... 

Inherent in the reduction of asymmetrically substituted cyclic imides is the problem of regiose-lectivity. Imides, in which one carbonyl group is part of a (thio)carbamate or urea function, usually show complete chemoselectivity for reduction of the other carbonyl group, indicated with an arrow. 

A polarographic study revealed one oxidation process to occur in acetone solution (59). The reduction waves reported have to be ascribed to the reduction of mercury dithio-carbamates, formed by a reaction of the electrode material (60). 

Although geneologically related to indoles, the dihydroindoles behave chemically rather like alkyl anilines. When diphenylamine reacts with chloro-propionyl chloride, amide 40 results this in turn readily cyclizes to oxindole 41. Sodium hydride followed by 2-chloroethyldimethylamine alkylates the 3-position (possibly through an intermediate aziridinium ion) partial demethylation is accomplished by refluxing with ethylchiorocarbonate, followed by hydrolysis of the intermediate carbamate to give indolinone 42, the antidepressant amedalin Repetition of this sequence on the chloropropyl homologue, followed by reduction of the appropriate indolinone produces dihydroindole 43, daledalin, which also has antidepressant activity. ... 

The isolation of calycanthine (9) in 1888 by Eccles [28] and the subsequent proposition for its origins in the oxidative dimerization of tryptamine by Woodward [29] and Robinson [30] had prompted several key synthetic studies based on a biomimetic approach. Hendrickson was the first to experimentally verify the plausibility of forming the C3-C3 linked dimers through an oxidative radical dimerization strategy (Scheme 9.2a). He demonstrated that the sodium enolate of a tryptamine-derived oxindole could be oxidized with iodine to afford a mixture of three possible stereoisomers. The racemic product was isolated in 13 % yield, while the meso product was isolated in 8 % yield. Global reduction of the oxindole and carbamates afforded the first synthetic samples of chimonanthine (7) [9a],... 

Hong et al. (2004) also found that modification of PAMAM dendrimers with a short PEG linker arm could act to reduce nonspecificity caused by the amines on the dendrimer-modified surface. An azido-PEGj-aininc spacer was activated with nitrophenyl carbamate to yield an activated intermediate that could be used to modify the amines on the dendrimer (Figure 7.24). Reaction at high molar ratio resulted in about 61 PEG-azido spacers on the dendrimer. Reduction of the azido group to an amine using triphenylphosphine in THF provided the dendrimer-PEG-amine derivative for surface modification. The added presence of the PEG spacer arm reduced... 

Four approaches to the synthesis of 4(5)-aminoimidazoles (25) have been described and are summarized in Scheme 1. These are (a) reduction of 4(5)-nitroimidazoles (27), (b) hydrolysis of carbamates and amides (28),... 

Aminoimidazole (25 R = H), which was generated in situ either by reduction of 4(5)-nitroimidazole (27 R = H) (Section III,A,1) or by hydrolysis of f-butyl-imidazole-4-carbamate (Section III,A,2) was diazotized in situ in tetrafluoroboric acid to give 4-fluoroimidazole (73JA4619, 73JOC3647). Diazotization was also successfully performed on the dihydrochloride salt of 4(5)-aminoimidazole (25 R = H) (87JOC5538). 

The syntheses of these three compounds share a common route as described by Brickner et al. [53] and Barbachyn et al. [54]. Namely, the coupling reaction of 3,4-difluoronitrobenzene (82) with piperazine, morpholine, or thiomorpholine to yield the corresponding 4-substituted 3-fluoro-nitrobenzene (83), which upon reduction gives rise to the aniline derivative (84). Carbobenzoxy protection of the active nitrogen of 84 using benzyloxy-carbonyl chloride (CbzCl) results in the formation of carbamates 85a and 85b. Treatment of 85a,b with n-BuLi and (i -glycidyl butyrate yields a 5-(R)-... 

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. 

Xenovinine 195, a natural alkaloid, was obtained by catalytic hydrogenolysis of carbamate 194 and subsequent intramolecular reductive amination of the in /-////-generated A-deprotected ketopyrrolidine <1999T8915>. Enantiodivergent synthesis of 195 with the same reductive amination as final step was also reported (Scheme 45) <1998EJO 955>. 

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