Carbonic acid anhydride

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. 

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 ... 

Benzoylation of benzoylmethylene triphenylarsorane (20) with benzoyl bromide gave a kinetically controlled acylated product, which on treatment with sodium acetate in chloroform afforded thermodynamically controlled dibenzoylmethylene triphenylarsorane (21) (56). Acylation with carbonic acid anhydride (32, 56), phenylisocyanate (32), or chloroformic ester (32) gave in no case O-acylated product. Similarly, reaction with acetic anhydride afforded l,3-dioxo-l-phenyl-butylidene-(2)-triphenylar-sorane (56). 

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). 

Though CO is formally the anhydride of formic acid, its solubility in water and bases is slight. It will give formates when heated with alkalis, however. As just noted, Q02 gives malonic acid. However, C02 is by far the most important carbonic acid anhydride, combining with water to give carbonic acid, for which the following equilibrium constants are conventionally written ... 

SYNS ANHYDRIDE CARBONIQUE (FRENCH) CARBON DIOXIDE, refrigerated Uquid (UN 2187) (DOT) CARBON DIOXIDE, soKd (UN 1845) (DOT) CARBONIC ACID ANHYDRIDE CARBONIC ACID GAS CARBONIC ANHYDRIDE CARBON OXIDE DRY ICE DRY ICE (UN 1845) (DOT) KHLADON 744 KOHLENDIOXYD (GERMAN) KOHLENSAEURE (GERMAN) R 744... 

Results to 3 One method giving polyphenylalanines (19) starts from the diazide (15 o) and others reacting with 4-benzyl-24 dioxo-oxozolidinc in pyridine (Eq. 9). Polypeptides containing the porphyrins in various ratxK are obtained. Now from stereoisomeric N-carbonic acid anhydrides of phenylalanines the D-, L- and DJL-fonns of fte polyphenylalanines were prepared. 

For efficient peptide bond formation acid halides azides 2,b l and Leuchs anhydridesb l were employed as the first activated species in peptide synthesis. Since then, besides considerable improvements to the azide (see Section 3.1) as well as the V-carboxyanhydride 7 procedure d (sgg Section 3.4.3), the methods have evolved over decades along a few basic principles as outlined in Scheme 2. The symmetrical the mixed carboxylic acid 4,b 5s] and the carbonic acid anhydrides were developed and remain useful despite the... 

Scheme 1 Mixed Carboxylic Acid Anhydrides 1, Mixed Carbonic Acid Anhydrides 2, Symmetrical Anhydrides 3, Al-Carboxyanhydrides 4, iV-Thiocarboxyanhydrides 5, Al-Substituted iV-Carboxyanhydrides 6, and Urethane-Protected Al-Carboxyanhydrides 7...

Where acid chlorides are difficult to obtain, Weinstock s method of using mixed carboxylic-carbonic acid anhydrides can be helpful. The acid to be converted into its azide is treated with ethyl chlorofor-mate and base, the ethyl carbonate moiety is then displaced by azide ion. The method has been used in the penicillin field . It is not general, however when the alkanoyl part of the mixed anhydride is sterically hindered, the azide ion displaces it instead of the carbonate moiety, and ethyl azidoformate is produced Cyclic anhydrides can be opened by azide ion, to give the salts of omega-azidocarbonyl acids, such as Na+ "OOCCHaCHaCONa . 

Henklein, P., and Glode, J., Unusual aminolysis of a carboxylic acid-carbonic acid anhydride, Z. Chem., 29, 19, 1989. 

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