Substituent reaction

In the 1,2,4-thiadiazole ring the electron density at the 5-position is markedly lower than at the 3-position, and this affects substituent reactions. 5-Halogeno derivatives, for example, approach the reactivity of 4-halogenopyrimidines. The 1,2,4-oxadiazole ring shows a similar difference between the 3- and 5-positions. 

Woodward s synthesis, 4, 416-419 Chlorophyll b, 4, 382 Chlorophyll c, 4, 382 Chlorophyll d, 4, 382 Chlorophylls, 4, 378 biosynthesis reviews, 1, 99 structure, 4, 370 substituents reactions, 4, 402 Chloroporphyrin e, 4, 404 Chloroprothixene pharmacology, 3, 942 Chloropyramine as antihistamine, 1, 177 Chloropyrifos synthesis, 2, 201 Chloropyrifos-ethyl as insecticide, 2, 516 Chloropyrifos-methyl as insecticide, 2, 516 Chloroquine, 1, 145 adsorption on nucleic acids, 1, 179 as antimalarial, 1, 173, 2, 517 Chloroquine, hydroxy-as antimalarial, 2, 517 Chlorosulfonyl isocyanate cycloaddition reactions... 

Schotten-Baumann reaction, 5, 745 stability, 5, 744 structure, 5, 736-743 substituents reactions, 5, 83... 

According to earlier considerations, the effects of m-substituents have been considered generally to be of the sigma zero type. Swain and Lupton have questioned this conclusion. We have proceeded in the following manner to obtain evidence on the issue. From all the known data, 11 sets of meta substituent reaction series data were found which meet the minimum substituent criterion for basis sets. These reactions are listed in Table XI, with the pT .Pr. ... 

Many radical reactions do show the expected small and non-specific response to substituents. Reaction 14 of Table XIV is an example it has a value of p not significantly different from zero and shows almost a random response to the polar nature of the substituent.438 The dissociation of hexaphenylethanes is obscured by experimental uncertainties but seems to be increased by both electron-releasing and electron-withdrawing substituents. 

Hydrosilylation of monosubstituted and. em-disubstituted olefins (Reactions 5.3 and 5.4) are efficient processes and have been shown to occur with high regioselectivity (awti-Markovnikov) in the case of both electron-rich and electron-poor olefins [25]. For cis or trans disubstituted double bonds, hydrosilylation is still an efficient process, although it requires slightly longer reaction times and an activating substituent (Reaction 5.5) [25]. Any hydrosilylation product has been observed with 1,2-dialkyl-and 1,2-diaryl-substituted olefins, due to the predominant reversible addition of (TMS)3Si radical to the double bond [19]. 

As noted earlier, most classical antidepressant agents consist of propylamine derivatives of tricyclic aromatic compounds. The antidepressant molecule tametraline is thus notable in that it is built on a bicyclic nucleus that directly carries the amine substituent. Reaction of 4-phenyl-l-tetralone (18) (obtainable by Friedel-Crafts cyclization of 4,4-diphenyl butyric acid) with methyl amine in the presence of titanium chloride gives the corresponding Schiff base. Reduction by means of sodium borohydride affords the secondary amine as a mixture of cis (21) and trans (20) isomers. The latter is separated to afford the more active antidepressant of the pair, tametraline (20). 

The addition-elimination mechanism is also very common in the monocyclic oxygen and sulfur heterocycles (e.g. equation 20), a fact frequently cited as evidence for their low aromaticity. Pyran-2-ones can react with electrophiles at the 3- and 5-positions and pyran-4-ones at the 3-position (they also react at the carbonyl oxygen atom, but this is classified as a substituent reaction). Moreover, while the position of substitution can often be predicted on the basis of charge distribution and substituent effects, the choice of experimental conditions can also profoundly affect the outcome of the reaction, as illustrated in Schemes 2 and 3. 

Pyridinones and quinolinones undergo electrophilic attack at the (3 -position (12,13) fairly easily and disubstitution is well known in the pyridine series. Pyridinones are more easily halogenated than benzene, but the highly acidic conditions used for nitration and sulfonation makes these less easy reactions. Electrophiles also attack at the oxygen (14), but this is considered as a substituent reaction and therefore will be dealt with in Chapter 2.06. 

Substituent Reaction Conditions Yield of Products (%) Major Minor ... 

Two other important modes of substitution require mention here. They are the SNAr and elimination-addition reactions. Actually, it is sometimes difficult to distinguish between true aromatic nucleophilic substitutions and addition-elimination processes. The second group involves pyridyne intermediates (Scheme 53). Both of these reaction types are discussed fully under substituent reactions (Chapter 2.06). 

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