Side reactions acyl shifts

Two side reactions, the O to N acyl shift and racemization, limit the application to some extent. Lower reaction temperatures, shorter reaction times or the use of unsymmetric carbodiimides suppress these reactions. The addition of reactive nucleophiles will be discussed in a later section (active esters). 

A short route to 5-monosubstituted oxazoles is based on the flash vacuum pyrolysis of azolides of 1,2,4-triazole (169) <89H(29)103>. 5-Aryloxazoles are obtained in excellent yield, but the formation of ketene is a major side reaction for alkyl analogues with an a hydrogen. The rearrangement is believed to proceed by [1,5] sigmatropic shift of the acyl substituent followed by loss of nitrogen and cyclization of a diradical intermediate (Scheme 79). 

Side reactions such as double-bond migration and others are observed, similar to hydroformylation. Mechanistically, hydrocarboxylation is related to hydroformylation up until the metal acyl formation stage13. The presence of an acidic compound shifts the reaction towards formation of carboxylic acid derivatives and suppresses reductive elimination which forms aldehydes. The mechanism of the final steps is unclear13. 

Photochemical transformations of 3/f-oxepin-2-ones resemble that of muconic anhydrides (see above), but are complicated by side reactions. Thus, UV photolysis of 3,3-dimethyloxepin-2-one ( 20°C, in acetone) gives besides the expected bicyclic lactone (19), an isomeric by-product (20) the yield of the latter was increased with increasing temperature (Equation (5)) <84JCS(Pl)769>. On 2-acetylnaphthalene-sensitized photolysis of 3-acyl-3-methyloxepin-2-ones, the 1,5-acyl shift plays an important role giving, for example, 7-acetyl-3-methyloxepin-2-one, as the main product <85JCR(S)70>. 

The examples of 1,2-acyl shifts displayed at the lefthand side of the Eqs. (1—7) and in Eqs. (16—18) show that the oxa-di- t-methane rearrangement as a reaction of the triplet state of p,Y-unsaturated ketones... 

As a further consequence of the high reactivity of the excessive 0-acyl isourea in the heterogeneous peptide synthesis mixture, a base-catalyzed intramolecular 0-N-acyl migration takes place, forming the inactive N-acyl dicyclohexylurea. At the same time, this by-product is formed by acylation of already formed still dissolved amounts of dicyclohexylurea, which can be attacked by the symmetric anhydride or the 0-acyl isourea of the carboxylic component as well. Both the N,0-acyl shift and the latter side reaction decrease the total concentration of the activated masked amino acid even N,N -diacyl derivatives of the urea also can be formed as further by-product. Fortunately, all of these acyl urea derivatives are not fixed to the polymer phase and are well soluble in dichloromethane, so that they can be washed out easily from the gel phase after the... 

The light-brown oil with molecular formula of C22H32O0 and a specific optical rotation of -172 at the Nap-line in iso-octane, displays nearly identical spectrometric and chemical properties as humulone. In the H NMR spectrum the methine proton of the acyl side chain is shifted between 5 1 and 5 2, while an additional methylene function absorbs in this region also. Since the spectrometric changes did not allow unequivocal identification, chemical proofs have been worked out. In addition to the synthesis (see 2.4) prehumulone has been degraded in alkaline hydrogen peroxide (48). In the reaction mixture 4-methylpentanoic acid has been isolated corresponding to oxidative fission of the acyl side chain (49). It follows that prehumulone is (-)(6R)-4,6-bis(3-methylbut-2-enyl)-3,5,6-trihydroxy-2-(4-methylpentanoyl)cyclohexa-2,4-dienone (10, Fig. 12). 

The acyl ureas are the main side products at elevated temperatures, and in order to shift the reaction toward peptide bond formation, temperatures around 0° should be used. Presence of an amino group during the reaction, also reduces the formation of acyl urea. The most commonly used carbodiimide for peptide synthesis performed in organic solvents is... 

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