Anhydride-amine reaction, equilibrium

Amine-anhydride reactions, equilibrium, 115 Anhydride-amine reaction, equilibrium, 115 Anhydride hydrolysis, polyimides, 58,60r,61/62 Aqueous ion extraction, kinetic model, 438-440 Aromatic polyimides applications, 67 properties, 26 structures, 27,28/ use as dielectric materials, 26... 

With the platinum-metal catalysts, this reaction can be suppressed by conducting the hydrogenation in acid solution or in acetic anhydride, which removes the amine from the equilibrium as its salt or as its acetate. For reactions with Raney nickel, where acid cannot be used, secondary amine formation is prevented by addition of ammonia. Hydrogenation of nitriles containing other functional groups may lead to cyclic compounds. For example, indoUzidine and quinoUzidine derivatives have been obtained in certain cases (7.21). 

Dmuchovsky, Vineyard and Zienty observed a quite unusual inverse isotope effect for k jkj of 0-65 for the base catalysed addition of n-butane-thiol-S-dj to maleic anhydride. While inconsistent with any model of a transition state involving S—H bond cleavage, the inverse isotope effect could be accounted for by postulating a pre-reaction equilibrium between butanethiol and triethylamine, much h ke the one in equations (10) and (11). In fact, substitution into equations (16) and (17) of 2566 and 1850 cm for the S—H and S—D stretching frequency, respectively, and 3253 and 2380 cm for the N—H and N—D stretches of the amine-thiol complex, yields an equilibrium isotope effect of 0-68 . 

A very surprising sulfone formation has been investigated by Oae and coworkers . On heating p-toluenesulfinic acid with dimethylaniline in ethanol for 15 h, the reaction mixture shown in equation 100 has been obtained. Obviously, the observed products arise from an equilibrium between the sulfinic acid and its pseudo-anhydride (disulfide trioxide), which is able to attack the amine nitrogen and degrade the tertiary amine corresponding to a Polonovsky reaction . 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

The next step in the reaction is the addition of acetic anhydride and sodium acetate. What will happen to the sodium acetate (NaOAc) in the aqueous solution of HCl Estimate the equilibrium constant for the reaction between NaOAc and HCl. Will there be enough acid left to keep the amine in solution ... 

This condensation is essentially an aldol-type reaction of an aldehyde with the methylene group of an anhydride. The sodium salt may be replaced by other basic catalysts such as potassium carbonate oi tertiary amines. If the acid residue in the anhydride is not the same as that in the sodium salt, an equilibrium between these substances may occur before condensation. Thus, a mixture of acetic anhydride and sodium butyrate or a mixture of butyric anhydride and sodium acetate gives cinnamic acid and a-ethylcinnamic acid in the same ratio. ... 

For some time considerable confusion existed as to whether the salt or the anhydride condensed with the aldehyde,9 10 for when benzaldehyde was heated with acetic anhydride and sodium butyrate, ethylcinnamic acid was found to be the main product.11 It is now quite clear, however, that it is the anhydride which undergoes condensation and that the sodium salt is simply the strongest commonly used base that will not destroy the anhydride. Thus acetic anhydride will condense with benzaldehyde in the presence of pyridine or triethyl amine whereas benzaldehyde, sodium acetate, and pyridine will not undergo the same reaction.12 When an acid salt different from the anhydride is employed, an equilibrium... 

An elegant application of the oxidation of 2-aminofurans has been described by Nicolaou and co-workers (02JA2190, 02JA2202) in model studies directed towards the total synthesis of CP molecules. In this study, the isolable iminobutenolide 80 is formed by cyclisation of the alkoxide 79 (Method B, Section II.B.l.b). Without a stabilising substituent on the ring the equilibrium favours the imine 80 rather than the amine 81 (Scheme 16). However, it is postulated that there is sufficient 2-ami -nofuran in equilibrium for this to be rapidly oxidised to the hydroperoxide 83. At this stage, the final product is determined by the reaction conditions. In strongly acidic conditions, tautomerism to the amine 85 and hydrolysis rationalises the formation of the isolated anhydride 88. Under weakly acidic conditions, formation of... 

This confirms the previously proposed mechanism of the monomethylamine imidiza-tion reaction except for the observed 1 1 dimethylamine/MMA stoichiometery. This stoi-chiometery indicates that the predominate reaction pathway of PMMA with dimethylamine probably involves two alkylations per anhydride (as in 2a -> 3a, Figure 2). The formation of amide at extreme reaction conditions could be due to a slower competitive amine acyl addition pathway (2c or addition to acid). Other possibilities include equilibrium reactions where high amine pressures could shift the equilibrium from, for instance, anhydride (3a and 3b) to amic-acid pair (4a and 4b). If the latter concentration is high enough, or leads to some statistically trapped groups, then some amides might survive the devolatilization conditions. 

Aniline (6) is converted to acetanilide (7) by acetylation according to the sequence shown in Equation 21.3. In this reaction, aniline is first converted to its hydrochloride salt 14. Acetic anhydride and sodium acetate are then added to give a mixture in which sodium acetate and 14 are in equilibrium with acetic acid and aniline. As free aniline is produced by this acid-base reaction, it rapidly undergoes acetylation by acetic anhydride to give acetanilide. This particular method for acetylating amines is general, and the yields are usually high. 

---