Activation effects groups

A quantitative study has been made on the effect of a methyl group in the 2-position of five-membered heteroaromatic compounds on the reactivity of position 5 in the formylation and trifluoroacetylation reaction. The order of sensitivity to the activating effect of the substituent is furan > tellurophene >selenophene = thiophene (77AHC(2l)ll9). 

Alkoxy-2,l-benzisoxazole-4,7-diones undergo ready nucleophilic displacement of the 3-alkoxy substituent, yielding 3-alkylamino and 3-dialkylamino derivatives with primary and secondary amines, respectively (67TL4313). In this instance the 4-carbonyl group apparently provides an activating effect. 

This topic has been reviewed [2, pp 94, 100-111, 130-134] All of the standard approaches to the synthesis of a compound like methyl 2-fluorostearate from methyl 2-bromostearate result mall yield of the 2-fluoro ester and the unsaturated esters. Although silver fluoride is not a new reagent, its use moist in wet acetonitrile to convert methyl 2-bromostearate to its fluoro ester is a departure from the traditional set of anhydrous conditions (Procedure 6, p 194) [71] In contrast, silver tetrafluoroborate converts a-chloroketones to their respective fluoroketones under anhydrous conditions. The displacement of less activated halogen groups by silver tetrafluoroborate to form their respective fluorides is novel Although silver tetrafluoroborate could not be used to convert an aliphatic terminal dichloromethyl or trichloromethyl group to its corresponding fluoro derivative, it is an effective fluorine source in other situations [72] (Table 8)... 

The AlCIs-catalyzed benzoylation of 2-methyl-5-phenyIthiophene to 2-methyl-3-benzoyl-5-phenylthiophene (118) is of certain interest for comparison of the activating effect of an alkyl and phenyl group. The structure of (118) was proved in an original way by conversion to (119) by an Elbs reaction. ... 

Competitive metalation of thiophene and 2-methylthiothiophene with a deficiency of n-butyllithium gave only 2-methylthio-5-thio-phenecarboxylic acid, showing the activating effect of the methylthio group. ... 

As to the electron-withdrawing substituents, the activating effect of a nitro group in the piperidino-dechlorination of 2-chloropyridine involves factors of 7.3 x 10 and 4.6 x 10 from the para and ortho positions, respectively. An ortho-cyano group was found to be... 

The A-oxidation of 3-chloropyridazines increases their reactivity toward methoxide and sulfanilamide anions.The reactivity of 4-chloro- or 4-nitro-quinoline and of chloropyridines toward methoxide ion and piperidine is less than that of the corresponding A-oxides (see Tables II and XI, pp. 270 and 338). The activating effect of the A-oxide moiety in 3-halopyridine A-oxides is greater than that of a nitro group, and in fluoroquinoline A-oxides the activation is transmitted to resonance-activated positions in the adjoining rings. 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

The activating effect of a trichloromethyl group is seen in the 2-dechlorination reactions of 2-chloro-4,6-bis(trichloromethyl)-s-tria-zine (175) with arylsulfonylhydrazides (24 hr) and heterocyclic amines (3 hr) at 20° and with unbasifled primary and secondary alcohols (65°, 30 min). The 4,6-diphenyl or 4,6-bis(4-chlorophenyl) analogs do not react in this manner. ... 

The activating effect of the phenylazo group in the reaction of 6-chloro-5-phenylazo-2,4-diaminopyrimidine and its analogs with amines or with dimethylformamide has been noted by Brown. The activating effect in 4-nitroso-, 4-phenylazoxy-, and 4-phenylazo-... 

The relation of the activating effects of an azine-nitrogen and a nitro group depends on the compounds chosen for comparison and on the nucleophile. The ratio of the rates of reaction of 283 (Table III, line 2) and of 284 (Table VII, line 1) is... 

Reaction of 2,4,7-trichloroquinoline with sodium methoxide (65°, 30 min) yielded an equal mixture of 2,7-dichloro-4-methoxy- (40%) and 4,7-dichloro-2-methoxy-derivatives (31%). The activating effect of the chloro groups is evident from the inertness of 4-chloro-quinoUne to methoxide ion at 65°. Alteration of the relative reactivity by cationization of the azine ring is again noted here in the acid-catalyzed hydrolysis (dilute HCl, 100°, 1.5 hr) of the trichloro compound to give 72% of the 2-hydroxylation product.Similarly, acid-hydrolysis of the alkoxy group proceeds much more readily in 2-ethoxy-4-chloro- than in 4-ethoxy-2-chloro-quinoline. ... 

---