Anhydrides disproportionation

Acetic acid is quantitatively converted to acetic anhydride by reaction with ketene. Mixed anhydrides are formed when homologs of acetic acid or aromatic acids are used in the reaction. Upon distillation at atmospheric pressure, the mixed anhydrides disproportionate into acetic anhydride and the symmetrical anhydride corresponding to the carboxylic acid. Yields of propionic, n-butyric, and w-caproic anhydrides prepared by this method are in the range of 80% to 87%. ... 

Phosphorus(III) Oxide. Phosphoms(III) oxide [12440-00-5] the anhydride of phosphonic acid, is formed along with by-products such as phosphoms pentoxide and red phosphoms when phosphoms is burned with less than stoichiometric amounts of oxygen (62). Phosphoms(III) oxide is a poisonous, white, wax-like, crystalline material, which has a melting point of 23.8°C and a boiling point of 175.3°C. When added to hot water, phosphoms(III) oxide reacts violentiy and forms phosphine, phosphoric acid, and red phosphoms. Even in cold water, disproportionation maybe observed if the oxide is not well agitated, resulting in the formation of phosphoric acid and yellow or orange poorly defined polymeric lower oxides of phosphoms (LOOP). 

The pyrolysis of a number of compounds at temperatures around 600— 800° and at pressures of the order of 10 2 mm. has been shown to give rise to benzyne. These compounds include for example indanetrione 29>, and phthalic anhydride 30 38>. The dimerisation of benzyne to yield biphenylene has been used preparatively 31 33>, an(j the pyrolysis of tetrafluorophthalic anhydride 34>, and tetrachlorophthalic anhydride 3i-33) gave the corresponding octahalobiphenylenes. In the case of the pyrolysis of tetrachlorophthalic anhydride some hexachlorobenzene is also formed, while the pyrolysis of tetrabromophthalic anhydride results in the formation of hexabromobenzene but no octabromobiphenylene. The disproportionation of tetrabromobenzyne to form carbon and bromine is a function of the high temperature involved and, as we shall see later, both tetrabromo- and tetraiodo-benzyne behave normally in solution. 

Chemically, nonmetals are usually the opposite of metals. The nonmetallic nature will increase towards the top of any column and toward the right in any row on the periodic table. Most nonmetal oxides are acid anhydrides. When added to water, they will form acids. A few nonmetals oxides, most notably CO and NO, do not react. Nonmetal oxides that do not react are neutral oxides. The reaction of a nonmetal oxide with water is not an oxidation-reduction reaction. The acid that forms will have the nonmetal in the same oxidation state as in the reacting oxide. The main exception to this is N02, which undergoes an oxidation-reduction (disproportionation) reaction to produce HN03 and NO. When a nonmetal can form more than one oxide, the higher the oxidation number of the nonmetal, the stronger the acid it forms. 

An additional minor source of urethane can be the reaction of unconsumed reagent with V-nucleophile (path C). Aminolysis of chloroformate occurs if there is an excess of reagent or if the anhydride-forming reaction is incomplete. The latter is more likely when the residues activated are hindered. This side reaction can be avoided by limiting the amount of reagent and extending the time of activation. A third side reaction that is of little consequence is disproportionation of the mixed anhydride to the symmetrical anhydride and dialkyl pyrocarbonate (see Section 7.5). 

FIGURE 7.7 Disproportionation of a mixed anhydride.14 Two molecules of anhydride generate symmetrical anhydride 8 and pyrocarbonate 9 probably via a bimolecular reaction.18... 

NL Benoiton, Y Lee, FMF Chen. Studies on the disproportionation of mixed anhydrides of IV-alkoxycarbonylamino acids. Int J Pept Prot Res 41, 338, 1993. 

Triethylamine (7) is a strong, hindered base originally employed for mixed-anhydride reactions. However, it reduces the rate of anhydride formation if the solvent is dichloromethane or chloroform (see Section 7.3) and promotes disproportionation of the anhydride under conditions in which /V-mcthylmorpholinc does not (see Section 7.5). It causes enantiomerization of urethane-protected amino-acid /V-carboxyanhydrides and reaction between two molecules with release of carbon dioxide (see Section 7.14). It is also used in the synthesis of Atosiban (see Section 8.9). There is no reaction for which it is recommended as superior to other tertiary amines, except possibly for coupling employing BOP-C1 (see Section 8.14). 

Acylation of arenes. These mixed anhydrides have been used Tor acylation of arenes. However these reagents are sensitive to moisture and tend to disproportionate. One solution is to generate the reagents in situ. Thus acyl trifluoro-acetates can be generated in the presence of the arene from a carboxylic acid, TFAA, and 85% phosphoric acid (as catalyst) in CHjCN. Ketones of the type O II... 

This minor product 23 and its diastereoisomers were also isolated,24 in 23% yield, when 15 was treated with acetic anhydride-pyridine. Thus, these products were assumed24 to have been formed by direct, double acetylation of the 5-C-phosphinyl group in 15, rather than by the previously proposed23 pathway involving the disproportionation of 15. 

Carboxylic mixed anhydrides are very important for the rapid synthesis of peptides by the stepwise procedure,however the use of carboxylic mixed anhydrides,e.g.those derived from pivalic acid and a protected amino acid (1),suffers from two disadvantages. Firstly,regiospecificity of attack at the desired carboxyl function is largely determined by steric effects and will not be 100% for all coupling reactions.Secondly,such mixed anhydrides have a propensity towards disproportionation to symmetric anhydrides which is highly undesirable in terms of reaction efficiency.This latter process can be depressed by operation of the reaction at -15 °C, but with the concurrent decrease in reaction rate and,on large scale manufacture,increased costs. 

Rate Constants (l.mol. s x 10 ) for the Disproportionation of Diphenylphosphinic-Amino Acid Anhydrides... 

Cava and Pollack s elegant synthesis of benzo[c]thiophene52 has been extended to the synthesis of, for example, naphtho[l,2-c]thio-phene (47),52 methyl benzo[c]thiophene-5-carboxylate,54 and 1,3-dimethyl- (48)55 and l,3,4,6-tetraphenylthieno[3,4-c]thiophene (49).56 The last compound is of particular interest because it is a remarkably stable (cf. compound 48 which only exists transiently) nonclassical thiophene containing ten n electrons for which the only uncharged resonance structure (49) contains a tetravalent sulfur atom. When the sulfoxide (50) is pyrolyzed over aluminum oxide, it gives the parent cyclic sulfide and 51 by disproportionation.57 However, when 50 is heated in acetic anhydride in the presence of iV-phenylmaleimide,... 

This compound melts at 23.9 °C and boils at 175.4 °C. Chemically, this oxide is the anhydride of phosphorous acid, H3P03. In the reaction with cold water, P406 does produce that acid. In hot water, disproportionation occurs and phosphine, phosphorus, and phosphoric acid are produced. At temperatures much above its boiling point, P406 decomposes into phosphorus and an oxide that can be described by the formula P 02 . 

---