Substituent effects carboxy groups

HMO calculations have been ultilized in the search for substituted thiepins liable to be good candidates for synthesis due to electronic substituent effects.7 Based on these results, the presence of at least two carboxy groups and one fluorine group give an increased resonance energy per electron to positive values, indicating at least some thermal stability. 

The TS proposed for these proline-catalyzed reactions is very similar to that for the proline-catalyzed aldol addition (see p. 132). In the case of imines, however, the aldehyde substituent is directed toward the enamine double bond because of the dominant steric effect of the (V-aryl substituent. This leads to formation of syn isomers, whereas the aldol reaction leads to anti isomers. This is the TS found to be the most stable by B3LYP/6-31G computations.199 The proton transfer is essentially complete at the TS. As with the aldol addition TS, the enamine is oriented anti to the proline carboxy group in the most stable TS. 

Also as noted above any substituents present have little effect upon such oxidations. In 2,2 -methylenedifuran (118) the rings are attacked simultaneously giving a tetramethoxy derivative.297 Even the bulk of the fert-butyl group has little effect.298 The only marked substituent effect is that exerted by an aromatic (benzene, thiophene, furan) residue which, if directly attached at the 2-position, promotes elimination instead of the addition of another methoxy group. The net process then becomes one of arylation, as when 2-(2-thienyl)furan (119) is oxidized to 120.298 There are reports that acetyl and carboxy groups can be ejected during oxidation, but that ester groups are usually retained.287... 

The presence of the electron-withdrawing trifluoromethyl substituent in the a-position has a dramatic effect on the reactivity of both the carboxy and the amino groups. The latter, in particular, shows a very marked decrease ( 4 units) in the pK.t value with respect to the corresponding natural amino acids, whereas the carboxy group experiences a more limited deviation (0.3-1.1 units) 111 As a consequence, activation of the carboxy group of... 

The cyclization can also be effected in the opposite direction, viz. at the sulfur atom as in (404). For this reaction the sulfur is introduced after the /8-oxoalkyl substituent has been attached to the nuclear nitrogen (78JMC489). The intermediate in this cyclization corresponds to the product from the acid-catalyzed Pummerer reaction of the 2,3-dihydrothiazolo sulfoxide (405) (81H(15)1349). When the (3-oxo group is part of a carboxy group or its derivatives, 3-hydroxythiazolylium derivatives are formed (408) (81H(15)1349>. 

A carboxy group is a rather weak electron-withdrawing substitutent and its electronic effect on the adjacent double bond is negligible. The fact that the straightforward synthesis of cyclo-propanecarboxylic acids via the addition of dichlorocarbene to alk-2-enoic acids has met with a little success is, therefore, due to the acidic properties of this substituent. 

The assignment of the quaternary C atoms at 154.3,152.1 and 116.4 ppm has yet to be established. The signal with the smallest shift (116.4 ppm) is assigned to C-3c because the substituent effects of carboxy groups on a-C atoms are small. Since the signal at... 

Linear correlations between pK and the Hammett substituent constant a, and between chemical shifts of the carbonyl carbon atom and a, for the four isomeric norbornene acids of gross structure (42) are explained by a perturbation effect between the electric dipoles of the carboxy-group and R (R= H, Cl, NO2, or OMe). The preparation of C-enriched samples of 1-substituted butanes and adamantylmethyl derivatives (label at C-1 and the exocyclic carbon atom respectively) has enabled direct comparison of vicinal coupling constants. The uniformly smaller... 

In an attempt to clarify the effects of ionic and hydrophobic substituents on the polyelectrolytic behaviour of polysaccharides, potentiometric titrations and activity measurements of the counter-ions have been conducted on carboxy-methyldextrans containing either substituted carboxy-groups or benzyl groups. Dextran glass (10 M, dextran) attached to an alkylamine-bonded phase of glass has been used for the hydrophobic immobilization of enzymes. ... 

As described in the Introduction, spontaneous racemization under alkaline condition is a typical feature of hydantoin. The rate of spontaneous racemization is very much influenced by the electronic properties of the C-5 substituent. Substituents with electronegative inductive effect will stabilize the enolate structure because electron density at C-5 is lowered, thus favoring the release of the proton at C-5. Therefore, hydantoins carrying a carboxy group on an alkyl side chain such as 5-(2 -carboxyethyl)hydantoin, and those carrying arylalkylated or aryl side chain, will readily racemize often within minutes. On the other hand, it may take hours to racemize merely alkylated hydantoins. Hydantoins are more or less unstable in the presence of alkali, and the equilibrium shifts to the direction of ring opening hydrolysis. 

Isoxazolines with alkyl substituents are also all liquids (or low melting solids) and incorporation of aryl substituents results in crystallinity. Introduction of carboxy substituents and endocyclic carbonyl or imino groups also has the anticipated effect, with crystalline products being isolated. These trends are illustrated by the data compiled in Table 2. 

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