Electronic effects aliphatic

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

The most widely used route to l-benzazepin-2-ones involves the Beckmann or Schmidt reaction of the easily accessible 1-tetralones. Many biologically active compounds described in this review have been prepared on the basis of these reactions they have been fully reviewed [2], In the Beckmann reaction of 1-tetralone oximes, polyphosphoric acid is used as a catalyst-solvent in most instances. Aryl migration generally takes precedence over alkyl migration under these reaction conditions, and various 1-tetralone oximes substituted on the aromatic and/or aliphatic rings can be converted to the appropriate 2,3,4,5-tetrahydro-l//-l-benzazepin-2-ones (51) [5, 20-23, 36, 59, 65, 80, 107-112]. Both courses of the rearrangement occur in some instances, yielding l-benzazepin-2-ones (51) and the isomeric 2-benzazepine-l-ones, probably due to electronic effects of the substituents [90, 113, 114]. 

The thio-Wittig reaction, like the Wittig itself, may involve (thia)phosphetane or betaine-type structures as intermediates. A combined experimental and theoretical study over a wide range of conditions and of substrates (aliphatic vs aromatic, aldehyde- vs ketone-derived) suggests a mechanistic continuity, with solvent polarity and substrate electronic effects being the main influences on the transition from one mechanism to another. ... 

A common probe of reaction mechanisms used to infer charge distribution in the transition state involves variation of substituent groups near the reaction center. From the variation in reaction rate produced by electron-donating and electron-withdrawing groups or by the steric hindrance of various sized groups, transition state characteristics can be inferred. Two empirical correlations have been proposed and refined which provide a common framework for this process. The Hammett equation is applied to aromatic systems [45]. The Taft correlation is applied to aliphatic systems [45], Definitions of terms, collections of substituent constants (steric and electronic effects for various substituents), and listings of observed reaction response parameters (for typical reaction types) have been collected [45]. 

Hammett s success in treating the electronic effect of substituents on the equilibria rates of organic reactions led Taft to apply the same principles to steric, inductive, and resonance effects. The Hammett o constants appear to be made up primarily of two electronic vectors field-inductive effect and resonance effect. For substituents on saturated systems, such as aliphatic compounds, the resonance effect is rarely a factor, so the o form the benzoic acid systems is not applicable. Taft extended Hammett s idea to aliphatics by introducing a steric parameter ( .). He assumed that for the hydrolysis of esters, steric and resonance effects will be the same whether the hydrolysis is catalyzed by acid or base. Rate differences would be caused only by the field-inductive effects of R and R in esters of the general formula (XCOOR), where X is the substituent being evaluated and R is held constant. Field effects of substituents X could be determined by measuring the rates of acid and base catalysis of a series XCOOR. From these rate constants, a value a could be determined by Equation (5.9) ... 

Because the electronic nature of substituents has little effect on the rate of acid-catalyzed hydrolysis of meta- or para-substituted benzoates (e.g., p for the acid hydrolysis of XC6H4COOR esters is close to zero), Taft suggested that the electronic nature of substituents will also have little effect on acid-catalyzed hydrolysis of aliphatic esters (Lowry and Richardson, 1987). Nevertheless, a strong electronic effect occurs in basic hydrolysis, as can be examined from the large p values for base-catalyzed hydrolysis of meta- or para-substituented benzoates. Hence, the effect of X on acid hydrolysis is purely steric but is a combination of steric and electronic effects in basic hydrolysis. Taft defined Es, a steric substituent constant, by Equation (5.11) ... 

Taft developed an analogous equation to correlate rate constants for reactions of aliphatic systems in which both steric and electronic effects often are important (Taft, 1953 Shorter, 1972) ... 

Several catalysts have been found for the ring opening of epoxides. For instance, cyclohexene oxide gave an excellent yield of the trans-fi-amino alcohol when treated with either aromatic or aliphatic amines in the presence of a scandium triflate catalyst.21 Aromatic epoxides react in a regiospeciflc reaction at the benzylic carbon when treated with aromatic amines and scandium triflate but at the least substituted carbon of the epoxide ring when aliphatic amines react. Electronic effects are more important in the reactions of the aromatic epoxides whereas steric factors control the reaction with aliphatic epoxides. 

Duthaler, R.O. and Roberts, J.D., Steric and electronic effects on 15N chemical shifts of saturated aliphatic amines and their hydrochlorides, J. Am. Chem. Soc., 100, 3889, 1978. 

In general, catalysis by 84a and 85c resulted in good to excellent enantioselec-tivities in the reduction of lcetimines derived from methyl aryl ketones and aromatic amines (80, R1, R3 = aryl, R2 = Me), where the electronic effects of substituents in both aromatic groups did not show any significant influence [79, 80]. On the other hand, imines obtained from aliphatic amines (80, R3 = alkyl) gave virtually racemic products with 85a [80b]. In the reduction of non-aromatic imines, such as 80c, only catalyst 84a maintained high enantioselectivity (Table... 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

From these findings it was rationalized that not only electronic effects control the formation of differently alkylated products. The steric demand of the aliphatic and aromatic substituents in the 2,6-position of the benzoate... 

The reaction of sulphides with (dichloroiodo)benzene can lead to several kinds of products depending on the substrate and the reaction conditions [19]. Sulphides of great structural diversity (aliphatic, aromatic, heterocyclic) were oxidized efficiently by (dichloroiodo)benzene (one equivalent) in aqueous pyridine. The reaction was almost instantaneous and not noticeably sensitive to steric or electronic effects. Ethylenic double bonds were not attacked under these conditions however, in vinylic sulphides containing an electron-withdrawing group (COOH or RSO) ft- to the sulphur atom the oxidation was accompanied by nucleophilic attack to the double bond resulting in a mixture of products. The method is suitable for the preparation of I80-labelled sulphoxides using small quantities of H2,80. 

Asymmetric allylboration of RCHO. (S)-l reacts with aliphatic or aryl aldehydes or with a,p-enals to form homoallylic alcohols in 92-97% ee and 80-92% chemical yield. The chemical and optical yields are higher than those obtained with B-allyldiisopinocamphenylborane (14,12), with allylboronates modified with tartrates, or with B-allyltrimethylsilylboronates. The high asymmetric induction is believed to result from steric effects rather than electronic effects. 

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