Carbamate function

Replacement of the carbamate function by an amide seems to be compatible with meprobamate-like activity in a compound formally derived from a 1,2-glycol. Oxidation of the commercially available aldehyde, 22, under controlled conditions affords the corresponding acid (23). This is then converted to its amide (24) via the acid chloride. Epoxidation by means of perphthalic acid affords oxanamide (25). ... 

For the preparation of spray-dried polyelectrolyte complexes, the polyanion was dissolved in dilute NH4HCO3 solution and mixed with the chitosan carbamate solution just before spray-drying. The excess NH4HCO3 decomposed thermally between 60 and 107 °C on the other hand, the carbamate function released carbon dioxide under the effect of the temperature at which the spray-drier was operated, thus regenerating chitosan at the moment of the polyelectrolyte microsphere formation (Fig. 5). 

The hydroxy groups in natural products like, for example, the macrolide antibiotics erythromycin, 1"1 and desmycosin, 2001 2011 as well as the 3-(hydroxymethyl)-2- or 3-cephems 2021 and derivatives of the amino sugar garamin 2031 have been converted into the carbamate function with CDI and amines. In the case of aminoglycoside antibiotics of the sisomicin series, thiocarbamates or dithiocarbamates have been prepared from alcohols or thiols using ImCSIm and amines.12041... 

Poly(boronic carbamatejs were prepared by alkoxyboration polymerization of diisocyanates with mesityldimethoxyborane (scheme 33).59 The polymers obtained have boronic carbamate functions in their repeating units and can be expected to be novel reactive polymers. First, alkoxyboration polymerization between mesityldimethoxyborane and 1,6-hexamethylene diisocyanate was examined, and the optimized reaction conditions were bulk reactions at 140°C. Both aliphatic and aromatic diisocyanates gave the corresponding polymers. When aromatic diisocyanates were employed, the... 

The use of ( )-enolcarbamates of type 1-56 allowed the generation of tetrahy-dropyrans 1-58 with complementary orientation of the carbamate functionality (Scheme 1.15). In all cases, the carbamate group adopts an axial orientation in the chairlike transition state 1-57. 

Polymers containing pendant carbamate functional groups can be prepared by the reaction of phenyl isocyanate with poly(vinyl alcohol) in homogeneous dimethylsulfoxide solutions using a tri-ethylamine catalyst. These modified polymers are soluble in dimethyl sulfoxide, dimethylacetamide, dimethylformamide and formic acid but are insoluble in water, methanol and xylene. Above about 50% degree of substitution, the polymers are also soluble in acetic acid and butyrolactone. The modified polymers contain aromatic, C = 0, NH and CN bands in the infrared and show a diminished OH absorption. Similar results were noted in the NMR spectroscopy. These modified polymers show a lower specific and intrinsic viscosity in DMSO solutions than does the unmodified poly(vinyl alcohol) and this viscosity decreases as the degree of substitution increases. 

Replacement of the carbamate group with isosteric functionalities such as an IV-methyl carbamate, urea, or amide group clearly confirmed the favorable qualities of the carbamate group [57], While the introduction of a urea group, as in case of iV-9-(tert-butylcarbamoyl)-9-desoxy-9-aminoquinine selector, instead of carbamate functionality turned out to be virtually equivalent in terms of enantiorecognition capabilities [57,58], the enantiomer separation potential was severely lost on iV-methylation of the carbamate group, like in 0-9-(N-me hy -N-tert-butylcarbamoyl)quinine [32,58], or its replacement by an amide, such as in case of Af-9-(pivaloyl)-9-desoxy-9-aminoquinine selector [57,58], For example, enantioselectivities dropped for DNB-alanine from 8.1 for the carbamate-type CSP, over 6.6 for thein-ea-type CSP, to 1.7 for the amide-type CSP, and 1.3 for the A -methyl... 

Interestingly, even derivative 113, with the carbamate-functionalized stereogenic center in the b-position, exhibited significant levels of diastereoselectivity to give ester 114 (Scheme 6.24). In this case, however, the syn addition product 114 was formed as the major isomer. 

Scheme 6.24. Diastereoselective cuprate addition to -carbamate-functionalized enoate 113.

The effects of solvent, temperature, and bulk of the silyl and carbamate functionalities on the stereoselectivity of Peterson olefination of silylated benzyl carbamates (Scheme 8) have been described. ... 

Reduced pyrrole derivative 130 is available from the oxidation of carbamate 129. The reaction proceeds via intramolecular participation of the nitrogen atom of the carbamate function as shown in Scheme 36 (94TH1). 

The first manufacturing route of the GEM side-chain relied on a-cyanoketone 125 however, the number of chemical steps from 125 to the final side-chain was reduced by one step (Noh et ah, 2004a). The sequence began with a selective hydrogenation with Raney nickel followed by double bond migration to enamine 131 (Scheme 4.25). The amino functionality of 131 was then monoprotected, and the double bond was reduced under hydrogenation conditions to afford pyrrolidine-3-one 133. Treatment of 133 with methoxylamine yielded methoxyoxime 129. Deprotection of the carbamate functionality was achieved with methanesulfonic acid to afford the C7-side-chain as the bis-methansulfonate salt. 

The next group of compounds that we want to look at are derivatives of carbamic acid (HO-CO-NH2), that is, the carbamates. Carbamates are widely used as herbicides and insecticides. The carbamate function exhibits both an ester and an amide-type functionality (Montgomery, 1997) ... 

Inorganic bases have been also employed in this system. When Butcher first used alkali carbonates [50], it was reported that, in DMF and at ambient temperature, the carbamation of primary and secondary aliphatic amines (or also arylamines) with alkyl halides under a C02 atmosphere (0.1 MPa) was effectively promoted by Cs2C03 [50, 51]. The Cs+ cations in the solvent used (DMF) did not form ion pairs with counterions, and favored the formation of naked carbamate anions that were more reactive at the O-ends with alkyl halides. Jung further found that the addition of tetrabutylammonium iodide (TBAI) to the system RR NH/ C02/RX/Cs2C03/DMF promoted the carbamation process with a higher yield and selectivity with respect to N-alkylation [51]. The process has been successfully extended to the synthesis of carbamate functionalities on solid phases. In this case, resin-bound carbamates are readily released from the resin by treatment with LiAlH4 in THF, yielding the respective N-methyl secondary amines [51]. 

First attempts to use the carbonate or the carbamate function for the covalent binding of amino acids and proteins applying the activation of dextran with phosgene showed that this approach is limited due to the fact that it is combined with a number of side reactions (Fig. 51) [355]. 

The product contains the carbamate functional group, which has characteristics of both an amide and an ester. Thus, the amine is protected as an amide, but the ester part of the carbamate can be readily removed. In fact, the /-butyl group of the carbamate can be removed by treatment with dilute acid. (This is the same SN1 process that is described in Section 23.3) The resulting carbamic acid is unstable and spontaneously eliminates carbon dioxide, regenerating the amine. An example is provided by the following equation ... 

TABLE 2. Effectiveness of enantiomeric separations for racemates (a)-(f) using carbamate-functionalized polysaccharides entries lA, IB, and IIB described in Table 1 with hexane/2-propanol, 90 10, v/v, as the mobile phase at a flow rate of 0.5 ml/min at 25 C. 

Although the factors controlling the formation of the cis- and frarcs-isomers are not easily defined, it seems reasonable that a double A1,2-type strain involving the carbamate functionality and the substituents is an important contributor. 

In another example, p-nitrophenyl chloroformate was required to introduce a sophisticated carbamate function in a multi-steps synthesis of retroviral protease inhibiting compounds (Ref. 26). The structure of the intermediate carbonate is given in scheme 30. 

The formation of cyclopropanols by C-O bond cleavage has been achieved under a variety of conditions (Table 1). In most cases the syntheses were carried out under acidic conditions, in the presenee of sulfuric acid, hydrochloric acid, pyridinium p-toluenesulfonate, boron tribromide, or an aqueous acid, to cleave esters, ethers, ° and acetals. Other acid-sensitive moieties in the substrate can react concomitantly under such conditions. Thus, when rer/-butyl-(l-ethoxycyclopropyl)carbamate was heated in hydrochloric acid at 60 "C both the ether and the carbamate functions reacted to give 1-aminocyclo-propanol hydrochloride. 1-Acetoxycyclopropanecarbonitrile, on the other hand, was converted to 1-hydroxycyclopropanecarbonitrile under similar conditions. ... 

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