Carbonic-carboxylic anhydrides

Carbomethoxybenzaldehyde, 30, 100 5-Carbomethoxy valeryl chloride, 38, 39 Carbon disulfide, 30, 57 39, 8, 78 Carbonic acid, trithio-, bis(carboxy-methyl) ester, 39, 77 Carbonic-carboxylic anhydrides, 37, 21 Carbon monoxide, 34, 14 Carbon oxysulfide, 32, 103 Carbon tetrachloride, 32, 27 37, 8 Carbonylation, of pyrogallol-1,3-dimethyl ether with hexamethylenetetramine, 31, 92 of pyrrole with dimethylformamide,... 

MnClj. The chloromanganese reagents can be used in THF, a more satisfactory solvent for the synthesis of ketones from mixed carbonic-carboxylic anhydrides (prepared by the reaction of carboxylic acids with ethyl chloroformate). 

Anderson, G.W. Zimmermann, J. G. Callahan, E M., Racemization Control in the Synthesis of Peptides by the Mixed Carbonic-Carboxylic Anhydride MethodPJ.Am. Chem. Soc. 1966, 88, 1338. 

A voluminous literature exists on the acidic surface groups and their characterization. Therefore, this aspect of carbon surface chemistry can be here treated relatively briefly. The acidity of these groups opens a convenient way for their determination by titration with aqueous or alcoholic bases. The total of the Bronsted acids, including phenols, reacts with aqueous sodium hydroxide solutions by neutralization adsorption, while carboxylic acids are neutraflzed already by the weak base sodium hydrogen carbonate carboxylic anhydrides (lactones). Lactones and lactols are opened to the carboxylate form by the stronger base... 

A resin with mixed carbonic-carboxylic anhydride function has been prepared and used as acylating reagent [144], Thus, the supported chloroformate 140 was obtained by reaction of hydroxymethylated polystyrene with phosgene in benzene (Scheme 7.43). Further treatment with benzoic acid in the presence of triethyl-amine in benzene gave rise to the supported mixed anhydride 141. This polymer has been used in the benzoylation of several amines, although variable amounts of benzoic acid from attack to the internal carbonyl were obtained when using aromatic amines. 

The polymer-bound mixed carbonic carboxylic anhydrides have re-... 

Tessler, M.M. and Rutenberg, M.W. (1972) Process for Reacting Ungelatinized Starch with a Mixed Carbonic -Carboxylic Anhydride of a Polycarboxylic Acid, U.S. Patent 3,699,095... 

The DCC peptide coupling method can be improved both in terms of yield and suppression of racemization by the addition of Lewis acids, especially zinc chloride. A promising pilot study on the use of polymer-bound carbonic-carboxylic anhydride functions for the preparation of amides has been reported. It has been suggested in two reports that peptide bond formation is more rapid when soluble polymers are used, specifically a, >-diaminopolyethyl-ene glycol ( amino PEG ) and chloromethylated polystyrene. ... 

Spontaneous hydrolyses of carboxylic anhydrides, diaryl carbonates and aryl chloroformates are faster in cationic than in anionic micelles, regardless of the nature of the counteranion in the cetyltrimethylammonium micelle (Al-Lohedan et al., 1982b Bunton et al., 1984). This charge effect does not seem to be related to substrate hydrophobicity, although the extent of micellar inhibition (relative to reaction in water) is clearly dependent upon substrate hydrophobicity for anhydride hydrolyses. 

It is reasonable to relate the values of k+fk at least qualitatively to the extents of bond making and breaking in the transition state. Bond making is all important in hydrolyses of carboxylic anhydrides, diaryl carbonates and methyl arenesulfonates. Bond breaking will be important in hydrolyses of alkyl halides and sulfonates, except for methyl derivatives, and especially so in water which can effectively solvate the leaving anion. 

JR Vaughan, RL Osato. The preparation of peptides using mixed carbonic-carboxylic acid anhydrides. J Am Chem Soc 74, 676, 1952. 

FMF Chen, M Slebioda, NL Benoiton. Mixed carboxylic-carbonic acid anhydrides of acylamino acids and peptides as a convenient source of 2,4-dialky 1 -5(AH)-oxazo-lones. Int J Pept Prot Res 31, 339, 1988. 

Selected examples of carboxylic acid anhydrides and carbonic hemiester anhydrides... 

Fig. 15.5 Oxygen and nitrogen surface groups on carbon, (a) lactone, (b) carboxylic anhydride,...

There are many electrophiles which not only terminate living polymer chains but also produce end-group substitution. For example, macromolecules with hydroxyl, carboxyl, thiol, or chlorine termini can be prepared by reacting living polymers with such compounds as epoxides, aldehydes, ketones, carbon dioxide, anhydrides, cyclic sulfides, disulfides, or chlorine (15-23). However, primary and secondary amino-substituted polymers are not available by terminations with 1° or 2° amines because living polymers react with such functionalities (1.). Yet, tert-amines can be introduced to chain ends by use of -N-N-di-methylamino-benzaldehyde as the terminating agent (24). 

In trying to formulate a reaction mechanism for the catalysis, the well known reaction of aluminum alcoholates with carboxylic anhydrides was used as a basis (14). For example, phthalic anhydride, maleic anhydrides, and carbon dioxide, will react so that the acid anhydride pushes itself between the metal atom and the alkoxy groups, thus separating them. This results in forming neutral aluminum salts of the monoalkyl carboxylic acids. It is possible, of course, for the conversion to proceed incompletely, having two alkoxy groups bound to the aluminum, thus having only 1 mole of acid anhvdride react on 1 mole of aluminum alcoholate. 

In solution-phase peptide synthesis, acylation of amino acids or peptides with N-protected azetidine-2-carboxylic acid is performed via the active esters, e.g. A-hydroxysuccin-imide 100 111-112 or pentachlorophenyl ester, m 117 as well as by the mixed anhydride 101114 or carbodiimide 118 methods. An attempt to prepare the A-carbonic acid anhydride by cycli-zation of A-(chloroformyl)azetidine-2-carboxylic acid with silver oxide in acetone or by addition of triethylamine in situ failed, presumably due to steric hindrance. 111 In SPPS, activation of the Fmoc-protected imino acid by HBTU 119,120 is reported. In solution-phase peptide synthesis, coupling of N-protected amino acids or peptides to C-protected azetidine-2-carboxylic acid or related peptides may be performed by active esters, 100 118 121 mixed anhydrides, 95 or similar methods. It may be worth mentioning that the probability of pip-erazine-2,5-dione formation from azetidine-2-carboxylic acid dipeptides is significantly reduced compared to proline dipeptides. 111 ... 

Amino groups react very easily with aldehydes or ketones, and with aldehydes in the presence of amines, they can be acylated by the usual acylating agents, and they react with amidacetals, Vilsmeier reagents and nitroso compounds (Scheme 12). As mentioned earlier, alkylation leads mainly to AT(2)-alkylated products. The hydrazino group reacts in the same way as the amino group with aldehydes or ketones, with acyl chlorides or carboxylic anhydrides, with sulfonyl chlorides, ortho esters, carbon disulfide and with nitrous acid. The last three reactions have mainly been used for the synthesis of condensed 1,2,4-triazines. 

The ATP-dependent carboxylation of biotin by bicarbonate is believed to control the transient formation of carbonic-phosphoric anhydride, or carboxyphosphate, as an active carboxylation intermediate ... 

Attempts to synthesize C-terminal peptide aldehydes using other reductive techniques are less successful. 24"29 The reduction of a-amino acid esters with sodium amalgam and lithium aluminum hydride reduction of tosylated a-aminoacyldimethylpyrazoles resulted in poor yields. 26,29 The Rosemond reduction of TV-phthaloyl amino acid chlorides is inconvenient because the aldehyde is sensitive to hydrazine hydrate that is used to remove the phthaloyl group. 27 28 jV -Z-Protected a-aminoacylimidazoles, which are reduced to the corresponding aldehydes using lithium aluminum hydride, are extremely moisture sensitive and readily decomposed. 25 The catalytic reduction of mixed carbonic/carboxylic acid anhydrides, prepared from acylated a-amino acids, leads to poor reproducibility and low yields. 24 The major problems associated with these techniques are overreduction, racemization, and poor yields. 

Reaction with Further Electrophiles of Group IVA (Sl,Ge,Sn). IV-Silylated aziridines can be prepared from ethyleneimine by amination of chlorosilanes in the presence of an HC1 acceptor, by dehydrocondensation with an organosilicon hydride or by cleavage of a silicon—carbon bond in 2-furyl-, 2-thienyl-, benzyl-, or allylsilanes in the presence of an alkali metal catalyst (262—266). N-Silylated aziridines can react with carboxylic anhydrides to give acylated aziridines, eg, A/-acetylaziridine [460-07-1] in high yields (267). At high temperatures, A/-silylaziridines can be dimerized to piperazines (268). Aldehydes can be inserted... 

Recent developments in this area include the use of poly[hydroxy(tosyloxy)-iodo]styrenes [80], chiral 2-(a-alkoxyalkyl) analogs of [hydroxy(tosyloxy)-iodo]benzene [81 - 83], and iodine(III)-phosphonate and -phosphinate reagents [84] for C-oxygen bond formation at a-carbon. Oxysulfonylations at the a-carbon atoms of carboxylic anhydrides with [hydroxy(sulfonyloxy)iodo]arenes have also been documented [85]. 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

All other carboxylic acid derivatives in Table 6.1, in which the leaving group is bound to the carboxyl carbon through an O atom, are increasingly better acylating agents than carboxylic acid alkyl esters (entry 3) in the order carboxylic acid phenyl ester (entry 4) < acyl isourea (entry 7) < mixed carboxylic acid/carbonic acid anhydride (entry 8) < carboxylic acid anhydride (entry 9) < mixed carboxylic acid anhydride (entry 10). 

FIGURE 2.32 Significant oxygen surface groups on a carbon surface (a) carboxyl, (b) lactone, (c) carbonyl, (d) ether, (e) pyrone, (f) phenol, and (g) carboxyl anhydride. 

LACTONIZATION Benzeneselenenyl chloride. Cesium carbonate. 1,2-Di-hydro-4,6-dimethyl-2-thioxo-3-pyridinecarbonitrile. Phenylthioacctyl chloride. Potassium hexamethyldisilazide. Silver perchlorate. Sulfuric acid. Tri-chlorobenzoic carboxylic anhydride. Trityl tetrafluoioborate. 

Mixed pivalic anhydride 18 (42) is an example of selective mixed carboxylic anhydride. Selective aminolysis could be caused by the steric hindrance of the fert-butyl group. A mixed carbonic anhydride strategy has also been smdied to... 

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