Carbamates from amides

Fig. 35. Preparation of methyl carbamates from amides with BTMA Br3...

En route to novel cyclobutene nucleosides, a HR on hydroxyamide 159 using PhI(OAc)2 gives cyclic carbamate 160 with less than 2% of the methyl carbamate. However, the use of PhI(OAc)2 is a powerful route to alkyl carbamates from amides. Thus, the syntheses of a-aminocyclopropanone... 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

The intermolecular coupling of lactams and acyclic amides has also been reported. Reactions of carbamates with aryl halides occurred in the presence of catalysts ligated by P(/-Bu)3.78 Both carbamates and amides coupled with aryl halides in the presence of a catalyst bearing Xantphos.90 In addition, the coupling of lactams with aryl halides has been successful. A combination of Pd(OAc)2 and DPPF first formed A-aryl lactams in good yields from 7-lactams, but the arylation of amides was improved significantly by the use of Xantphos (Equations (20) and (21)).90 91 The reaction of aryl halides with vinyligous amides has also been reported 92... 

TFA). Among various linkers studied in this work, the indole linker [21] was found to be the most suitable linker in terms of cleavage kinetics and actual cost. Rink linker was the second best in term of kinetics. The rate of cleavage of various functional groups linked to the above-mentioned resins was as follows sul-fonamide>carbamate urea>amide. Results from this study demonstrated that optimization of cleavage conditions often led to more suitable conditions and safer release of precious compounds synthesized on a solid support. 

Compounds in this dibenzocycloheptene series also manifest antidepressant activity when the trigonal one-carbon bridge is replaced by tetrahedral carbon. Thus, the reaction of hydrocarbon (24-7) with a metal amide in liquid ammonia leads to the corresponding carbanion (29-1). Treatment of that with the ethyl carbamate from A -methyl-3-chloropropylamine (29-2) leads to the alkylation product. The carbamate protecting group is then removed by sequential saponification with a base followed by acidification. This yields the antidepressant agent protriptyline (29-3) [30]. 

Carbamate and amide groups have been found to be stable under these coupling conditions73. In the presence of TiCLt or SnCLt, chiral a-keto amides 36 react with allyl-silane to produce, after hydrolysis, optically active tertiary alcohols 37 with extremely high optical selectivity (equation 23)74. The addition reaction appears to occur from the Si face of the carbonyl group. In a similar manner, a high degree of stereoselectivity is obtained from the reactions of A-Boc-a-amino aldehydes 38 with 2-substituted allylsilanes (equation 24)75. 

On the other hand, a similar activation has been found to be practically possible when carbamates or amides instead of amines themselves are used as the starting materials. The a cation formed from carbamates and amides is sufficiently stable to be trapped by nucleophiles in solution 17). 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

Prior to the recent paper by Buchwald, an intermolecular version of the arylation of carbamates was published by Hartwig et al. (Eq. (22)) [163]. His group showed that reactions catalyzed by a combination of Pd(OAc)2 and P(tBu)3 formed N-aryl carbamates from aryl bromides or chlorides and tert-butyl carbamate, but that this system was inactive for reactions of amides or sulfonamides. Again, the reaction conditions were not as mild as those used for animation, but they were similar to those employed in the reactions with Xantphos. For the intermolecular reactions, the use of sodium phenoxide as base was crucial. 

Base, on the other hand, cannot touch the f-Boc group—the carbonyl group is too hindered to be attacked even by OH-, and t-Boc is strongly resistant to basic hydrolysis again, another example of an amide with an Achilles heel. The obvious way to make carbamates from amines is to react them with a carbamoyl chloride—this is how Z-groups are usually put on. Unfortunately, f-BuOCOCl is unstable, and we have to use some other electrophilic derivative—usually the anhydride B0C2O as here, for example. 

The products obtained by the anodic oxidation of amides or carbamates in methanol have the same structures as the compounds which can be synthesized from amides (carbamates), aldehydes and methanol (equation 50). l e regeneration of iminium cations from these a-methoxyamides and subsequent reactions of the iminium cations with nucleophiles such as active methylene compounds or nucleophilic aromatic nuclei is well known under the term amidoalkylation (equation 50). ... 

As a final test of the synthetic strategy in the indolizidine alkaloid field, Weinreb turned to the fungal neurotoxin slaflamine (132) (82JA7065). Methylol acetate 125 was prepared in several steps from amide 124. When methylol acetate 125 was heated in refluxing o-dichlorobenzene, a separable 1 1.8 mixture of epimeric Diels-Alder adducts 127 and 128 (82%) was obtained via the N-acylimine intermediate 126. Catalytic hydrogenation of adduct 127, followed by basic hydrolysis, produced acid lactam 129. Curtius rearrangement of this compound led to carbamate lactam 131 (70JA7615) and to racemic slaflamine (132) (Scheme 18). 

Mg, MeOH, 8-75% yield. These conditions were used to cleave a tosyl group from an aziridine, a special case over normal amines. The reaction should work better with a benzenesulfonamide. This method is very good for carbamate and amide protected sulfonamides, but does not work with normal aliphatic amines. Since sulfonamides are readily acylated, this constitutes a relatively mild method for the cleavage of sulfonamides. Lactones and esters are compatible with this methodology. 

A more direct route has been used to prepare carbamates from aliphatic carboxylic acid amides (2.24).66... 

Haloformamidines are derivatives of formic acid the name haloforma-midines is used by Chemical Abstracts, which numbers the center carbon atom 1, and lists the nitrogens as N and N. However, this class of compounds is more closely related to carbamic acid, as evidenced by its synthesis from urea (carbamic acid amide) and cyanamide (carbamic acid nitrile). In a recent article ( ) concerned with the synthesis and reactions of substituted chloroformamidine hydrochlorides, the term carbamido chlorides was used. Since chloroformamidine hydrochlorides I are the amido chlorides of carbamide, this generic name is not unreasonable. There is no evidence for the isomeric geminate chloride structure II, and the polar character of I is evidenced by the relatively high melting points of chloroformamidine hydrochlorides, and by their insolubility in nonpolar solvents ( ). 

Figure 6 Reversed-phase packings with embedded groups. From top to bottom carbamate RPg, amide Cie urea type.

Another example of a conformationally restricted carbohydrate-derived library was reported by Overkleeft and coworkers. They prepared carboxyhc acid 30 in eight steps from D-mannitol (29) derived from o-matmose (Scheme 7.7). After coupling 30 onto the Rink amide linker, the hydroxyl and azide, upon conversion into carbamates and amides, respectively, furnished hw-olefln 32. The oxacycle core-contairung compounds 33 were generated upon RCM cleavage off solid-support. 

Fig. 25.6 Proposed reactions during the isocyanate treatment of GO where organic isocyanates react with the hydroxyl left oval) and carboxyl groups right oval) of graphene oxide sheets to form carbamate and amide functionalities, respectively (Reprinted with permission from Stankovich et al. 2006a, Copyright 2006 Elsevier)...

An improved method for the preparation of nitriles and thiocyanates from halides with benzyltrimethylammonium salts and a convenient preparation of both aliphatic and aromatic nitriles from aldehydes through N,N,N-trimethylhydrazonium salts have been reported. Nitriles can be easily converted into amidines with ammonium halides . Acylisocyanates can be conveniently prepared from amides with oxalyl chloride . A simple preparation of alkyl and aryl carbamates with N-carbonylsulfamic acid... 

Spry (1974, 1975b, 1977), at Lilly, prepared various C-3 N-acy derivatives including amides (190), ureas (191), carbamates (189), and thio-carbamates from the C-3 isocyanates (188). These cephalosporins, as indicated in Table XVIII, display gram-positive activity comparable to... 

LGA PROVIDED BY METAL IONS IN THE ACYL TRANSFER FROM AMIDES, UREAS, AND CARBAMATES TO SOLVENT ROH... 

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