Quinolines homolytic

Den Hertog and Overhoff - observed that when pyridine in sulfuric acid is added to molten potassium sodium nitrate the 3-nitro derivative is formed at 300°C, whereas at 450°C 2-nitropyridme is the main product. The latter is probably a free-radical process. Schorigin and Toptschiew obtained 7-nitroquinoline by the action of nitrogen peroxide on quinoline at 100°C, possibly through the homolytic addition of NOa. Laville and Waters reported that during the decomposition of pernitrous acid in aqueous acetic acid, quinoline is nitrated in the 6- and 7-positions. They considered that the reaction proceeds as shown in Scheme 3. 

The homolytic acylation of protonated heteroaromatic bases is, as with alkylation, characterized by high selectivity. Only the positions a and y to the heterocyclic nitrogen are attacked. Attack in the position or in the benzene ring of polynuclear heteroaromatics has never been observed, even after careful GLC analysis of the reaction products. Quinoline is attacked only in positions 2 and 4 the ratio 4-acyl- to 2-acylquinoline was 1.3 with the acetyl radical from acetaldehyde, 1.7 with the acetyl radical from pyruvic acid, and 2.8 with the benzoyl radical from benzaldehyde. 

A study of substituent effects in the homolytic acylation of 2- and 4-substituted quinolines with acetyl and benzoyl radicals has confirmed this character of the reaction. The benzoyl radical shows a higher nucleophilic character than the acetyl. This has been explained by the fact that the polar character originates in the contribution of the polar form (7) in the transition state. 

The low selectivity affects the synthetic interest of homolytic arylation from two points of view. The first concerns the position of substitution generally all the free positions are substituted, giving very complex mixtures of isomers. Thus, for example, quinoline gives all the seven possible isomers in appreciable amounts.This is in contrast to all the homolytic substitutions described in the previous sections, which lead to exclusive attack at the 2- and 4-positions. The other aspect concerns the conversions of the heterocyclic compounds, which are always very low, usually lower than 1%. If the conversions are high, the mixture of the reaction products becomes much more complex. Thus with quinoline it can be easily foreseen from the partial rate factors (Table IX) that not only all the possible 21 diphenylquinoline isomers, but also... 

Relative Rates and Partial Rate Factors fob Homolytic Phenylation or Pyridine, Quinoline, and Benzothiazole... 

Phenylation of quinoline with benzoyl peroxide is easier (qpl,nR 5.0) than that of pyridine (71BSF2612). Substitution takes place at all carbons, and partial rate factors (F2 = 3.3, F3 = 1.8, F4 = 5.4, Fs = 6.6, F6 = 1.5, F7 = 1.6, F8 = 9.6) were obtained at 1% conversion. Homolytic arylation of quinoline is not of much synthetic value as reactions taken to higher conversion suffer not only from lack of selectivity, but di- and poly-substitution also take place. 

A new process for the homolytic acylation of protonated heteroaromatic bases has been developed by Minisci et al. An A-oxyl radical generated from iV-hydroxyphthalimide by oxygen and Co(ll) abstracts a hydrogen atom from an aldehyde. The resulting nucleophilic acyl radical adds to the heterocycle which is then rearomatized via a chain process. Under these conditions, quinoline and benzaldehyde afford three products (Equation 108) <2003JHC325>. A similar reaction with 4-cyanopyridine gives 2-benzoyl-4-cyanopyridine in 96% yield. 

Minisci, F., Kintzinger, J. P., Porta, O., Barilli, P., Gardini, G. P. Nucleophilic character of alkyl radicals. VIII. Kinetics and mechanism of induced decomposition of decanoyl peroxide in the homolytic alkylation of protonated quinoline. Tetrahedron 1972, 28, 2415-2427. 

The introduction of an acyl group activates the heteroaromatic ring towards further acylation, which however always takes place exclusively at the positions X and y to the heterocyclic nitrogen (the protonated nitrogen is by far the main activating factor, which determines the positional selectivity). Thus, if a heterocyclic compound has two reactive positions, it is easy to obtain diacyl derivatives, but only one isomer (for example 2,4-diacylderivatives in the case of quinoline), whereas the monoacylderivatives prevail only at very low conversions. Due to the nucleophilic character of alkyl and acyl radicals, the behavior of homolytic... 

Particularly suitable models were provided by the homolytic substitutions of 4-substituted pyridines and 2- and 4-substituted quinolines, which are selectively attacked respectively in the positions 2, 4 and 2 by nucleophilic carbon free radicals. The positional selectivity is in fact always determined by the protonated heterocyclic nitrogen, wliich has a much more activating effect than the common substituents. 

Alkylation and arylation. The homolytic a-oxyalkylation of heteroaromatic bases using alcohols and ethers as radical sources has been studied. Although detailed experiments were chiefly concerned with quinoline and quinoxaline, benzothiazole was shown to yield 2-dioxanylbenzothiazole (40%) under the standard conditions. ... 

Radical Reactions.—Thiazolyl, pyridyl, and other heteroaryl radicals formed by aprotic diazotization of the corresponding heterocyclic amines substitute homolytically on thiophen with the formation of 2-heteroaryl-thiophens as the main products in 20—50% yield. The results of competitive experiments indicate that the reactivity of thiophen in this reaction at 70—80 °C is slightly higher than that of benzene. The currently accepted mechanism of the decomposition of benzoyl peroxide in thiophen has been criticized on the basis of new experimental results. No free thienyl radicals are involved in the reaction, as demonstrated by scavenging experiments, and the bithienyls formed are probably derived from dimerization of a benzoyloxythiophen radical a-complex, with subsequent loss of benzoic acid. Nitrene insertion into the thiophen ring has been observed in the thermal decomposition of 2-(2-azidobenzyl)thiophen and similar compounds, leading to thieno[3,2-6]quinoline derivatives. ... 

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