Carbamates from amines

With respect to the synthesis from amines, C02 and alkyl halides, the synthesis of carbamates from amines, C02 and alcohols (Equation 6.10) is not only a phosgene-free, but also a halogen-free process. Moreover, water forms as the only reaction coproduct. Whilst these features make the route very attractive from the point of view of environmental sustainability, unfortunately the reaction suffers from both thermodynamic and kinetics limitations. Kinetic impediments make necessary the use of a suitable catalyst which, moreover, must be water-tolerant in order to avoid deactivation by cogenerated H20. Several strategies have been explored to overcome these restraints, based mainly on the use of alcohols in a dehydrated form (for instance, as ortho esters or ortho carbonates) [63], or on the use of dehydrating agents [64, 65]. 

Scheme 6.19 Palladium-catalyzed generation of O-allylic carbamates from amines, C02, and allylic chlorides.

Synthesis of Carbamates from Amines, CO2 and Alkyl Halides... 

Scheme 5.12 PEG-enhanced synthesis of organic carbamates from amines, C02 and alkyl halides [50]...

Peterson SL, Stucka SM, Dinsmore CJ (2010) Parallel synthesis of ureas and carbamates from amines and C02 under mild conditions. Org Lett 12(6) 1340-1343... 

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. 

Fig. 6.30. Formation of carbamate from amines and carbon dioxide (adapted from...

Scheme 16.18 Synthesis of carbamates, from amines and electrochemicaUy activated carbon dioxide, in ionic liquid solutions (Reprinted from Ref [140] with kind permission of The American Chemical Society)...

Breitler S, Oldenhuis NJ, Fors BP, Buchwald SL (2011) Synthesis of unsymmetrical diarylureas via Pd-catalyzed C-N cross-coupling reactions. Org Lett 13(12) 3262-3265 Hooker JM, Reibel AT, Hill SM, Schueller MJ, Fowler JS (2009) One-Pot, Direct Incorporation of [ C]C02 into Carbamates. Angew Chem Int Ed 48(I9) 3482-3485 Peterson SL, Stucka SM, Dinsmore CJ (2010) Parallel synthesis of ureas and carbamates from amines and CO2 under mild conditions. Org Lett 12(6) 1340-1343 Wei Y, Liu J, Lin S, Ding H, Liang F, Zhao B (2010) Acetoacetanilides as masked isocyanates facile and efficient synthesis of unsymmetrically substituted ureas. Org Lett 12 (19) 4220 223... 

Honda, M. Sonehara, S. Yasuda, H. Nakagawa, Y Tomishige, K. Heterogeneous CeOj Catalyst for the One-Pot Synthesis of Organic Carbamates from Amines, CO and Alcohols. Green Chem. 2011,13, 3406-3413. 

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

The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate salts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pKg value of the base to ensure almost complete formation of the cation. They are extracted with diethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines (isocyanides) are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

Carbon dioxide reacts with amines (ArNH2) and iodoethane, under electrolysis conditions, to give the corresponding carbamate, (ArNHC02Et). Urea derivatives were obtained from amines, CO2, and an antimony catalyst. ... 

Klan et al. proposed that both alcohols and amines are initially released as carbonates and carbamates from 44 these undergo thermal decarboxylation to release CO2 and form their respective alcohols and amines.Furthermore, the chemical yields of the protected amine were reduced since they were involved in electron transfer reactions that decomposed 44. 

Scheme 10.1 Selective formation of enol carbamates from secondary amines, CO2, and terminal alkynes.

Carbamates can be prepared by O-alkylation of carbamic acids R2N-CO2H. Carba-mic acids are usually susceptible to decarboxylation, but the corresponding salts can be prepared from amines and carbon dioxide under basic reaction conditions and... 

Table 14.8. Preparation of carbamates from support-bound amines or isocyanates.

Few solid-phase syntheses of oxazoles have been reported (Table 15.17). The most general strategy is the dehydration of a-(acylamino) ketones (Entry 2, Table 15.17) or 2-(acylamino)phenols (Entry 1, Table 15.17). Oxazolidin-2-ones have been prepared by intramolecular nucleophilic cleavage of carbamates from insoluble supports (Entries 5 and 6, Table 15.17). Resin-bound 2-aminoethanols, which are accessible by nucleophilic ring-opening of oxiranes with amines, undergo cyclocondensation with aldehydes to yield oxazolidines [220,221]. These compounds are unstable towards acids, and can be released from the support only under neutral or basic reaction conditions. 

Scheme 6.7 Synthesis of carbamates from aliphatic primary amines and dimethyl carbonate (DMC) in the presence of C02. The catalytic role of C02.

Scheme 6.15 Synthesis of cyclic carbamates from chloromethyl oxirane, primary aliphatic amines, and C02.

Pd(0)/phosphine complexes, or their precursors, in the presence of a suitable co-base, have also been shown to promote, in good yields (66-100%), the formation of allylic carbamates from various primary and secondary aliphatic amines, pressurized C02 and allylic chlorides, in THF, at ambient temperature [87a]. The choice of the added co-base (Base), used for generating the carbamate salt RR NC02 (BaseH)+, was found to be critical for high yields of O-allylic urethanes. The use of a guanidine (CyTMG) or amidine (DBU) base was optimal for this system (see also Section 6.3.1). ft is assumed that this chemistry passes catalytically through a mechanism similar to that illustrated in Scheme 6.19. This involves nucleophilic attack by carbamate anion on a (tt-allyl) palladium species, formed by the oxidative addition of the allylic chloride to a palladium(O) intermediate. 

Coupling of amine 12 and chloroformate 13 is similar to the preparation of amides from amines and carboxylic acid chlorides (see Chapter 14). Secondary amine 12 attacks the activated carbonyl group. Elimination of HC1, which is trapped by NEt3, provides carbamate 14. 

An efficient and environmentally benign method for the PEG400-enhanced synthesis of organic carbamates with high chemoselectivity from amines, CO2 and alkyl halides under room temperature and atmospheric pressure utilizing K2CO3 as a base is reported (Scheme 5.12) [50]. PEG probably could serve as both a solvent and PTC, and also activate the carbamic anion so that PEG could depress the alkylation and enhance the selectivity toward the target product. 

An intermolecular version of the arylation of carbamates has been recently published by Hartwig et al. (Eq. (21)) [132]. His group showed that reactions catalyzed by a combination of Pd(OAc)2 and P( -Bu)3 formed /V-aryl carbamates from aryl bromides or chlorides and f-butylcarbamate as substrate. Again, the reaction conditions were not as mild as those for amination, but were similar to those of the intramolecular reactions. For the intermolecular reactions, the use of sodium phenox-ide as base was crucial. Reactions using Cs2C03 showed low conversions. Those involving NaO-r-Bu as base rapidly formed a gel, presumably from the deproto-nated carbamate, and also showed little or no conversion. The products of these reactions serve as conveniently protected anilines, and r-butylcarbamate can be considered one type of ammonia surrogate. In addition, the products of these reactions are suitable for subsequent directed metalation procedures [100]. 

Free amino acids in musts are of paramount importance, since they constitute a source of nitrogen for yeasts in alcoholic fermentation, for lactic acid bacteria in malolactic fermentation and can also be a source of aromatic compounds. In certain cases, some amino acids can produce undesirable compounds in wines, such as ethyl carbamate, biogenic amines, ochratoxin A (from 2-phenylalanine) and 3-carbolines (from tryptophane) (Herraiz and Ough 1993 Herraiz et al. 1993). 

Examples of gold-catalyzed carbonylation of amines and olefins exist related to the activation of carbonyl. The first case involves the formation of carbamates from anilines and CO in the presence of alcohols or the production of acetamides from aliphatic amines. In these examples, Au(I) (usually [AuCl(PPh3)]) catalysts are preferred. For the carbonylation of olefins, gold(I) carbonyls are prepared in situ in sulfiu ic acid media to afford carboxyhc acids. ... 

In 1986, Sasaki and Dixneuf reported the first example of the Ru3(CO)i2-catalyzed formation of vinyl carbamate from terminal acetylene, CO2 and secondary amines (Eq. 11.83) [149, 150]. 

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