Temperature Temperature can alter not only the rate of vapor phase halogenations but also the nature of the products [rule 4 , Section 11,C, Previously the uncertainty was expressed as to whether kinetic or thermodynamic factors underlie this behavior. Others have assumed, without sound evidence, that kinetic factors are decisive and that the change in orientation signifies a switch in mechanism from electrophilic to radical character. However, further speculation on this point must await equally imaginative experimentation.
Kinetic Consequences Further analysis of existing models for direct electrophilic or radical substitution cf. Section ,A for the distinction between a direct substitution and an addition-elimination pathway would include relatively low-energy charge-transfer complexes 16 and 20 and possibly an intermediate 18 of higher energy [Eq. Kosower and G. Wu, J. With certain electrophiles bridging forms of intermediate 18, possibly analogous to the halonium ions of olefinic systems, may be better representations. Whether bond making transition state 17 or bond breaking transition state 19 is of higher energy often may be revealed by the kinetics.
It should be remembered, however, that the existence of intermediate 18 and hence of a two-step process is only a postulate. In certain cases 18 might be sufficiently stable to permit verification of its presence. Quantum Mechanical Correlations At present, the most extensive data on heterocyclic halogenation concern the sites of substitution under different experimental conditions. The latter approach adjudges configuration 18 as the better model for T.
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Since insights from aromatic substitution favor an sp3-hybridized transition state, and since the thermic postulate would assign similar configurations to 17, 18, and 19,Q2some type of localization calculation seems to be a more promising approach to the desired structure-reactivity correlation. Unfortunately, the worth of such calculations is still obscured both..
Wiley, New York, EISCH The most successful contribution to this field has been the calculation of localization energies for protonated aza-aromatic heterocycles and their use in predicting sites of nitratione3 cf, Section ,E. I n truth, the agreement between such calculated parameters and experimental findings is quite limited a t present and any divergence between such calculations and the facts is not a t all decisive in formulating such substitutions.
A recent, discerning assessment of such theoretical approximations has also reached this disheartening conclusion. I n the following section the generality of such a qualitative transition state view will be examined. Monocyclic Systems I n broad terms, the sites of heterocyclic halogenation follow the relative stabilities of the possible tetrahedral transition states, as assessed by a qualitative resonance treatment.
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For electrophilic attack the more stable transition states will be those permitting maximum positive charge dispersal, while disrupting a minimum of aromatic sextets and avoiding the positioning of the charge on electronegative heteroatoms. For five- and six-membered heterocycle transition states 21 and 22 understandably are the favored configura- 21 22 tions.
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Such a view unifies t,he substitutional behavior of furan, pyrrole, pyrazole, thiophen, pyridine, pyrimidine and 4-pyrone. I, Chapter 2. Academic Press, New York, Katritzky, T 2. Benzo Derivatives With benzo derivatives, competition for the halogen between benzenoid and heterocyclic rings must be considered. To explain the preference for attack in the hetero ring [rule l ,Section 11,C, 21 and the resulting orientation, it may be useful to recall that disruption of aromatic conjugation becomes increasingly facile in polycyclic systems.
I n the case of thianaphthene and indole, the intervention of diadducts of the benzofuran type may be responsible for substitution at C Preferential proton abstraction from C-3 may occur because of its benzylic character. Subsequent halide ion elimination would yield the halo derivative [Eq. The widely accepted intervention of halonium ion intermediates in halogen additions to olefinsQ5suggests that fully covalently bonded adducts of type 23 need not be formed in heterocyclic halogenation.
For quinoline and isoquinoline intermediates of type 24 seem reasonable possibilities, as does 25 for thianaphthene and indole halogenations. Their formation would be favored by removing an exocyclic olefinic linkage from conjugation and their destruction to yield substitution product 95 J. Traynham, J. The greater ability of C-4 in the quinoline system and C-3 in the isoquinoline system to tolerate an electron deficiency accords with the transition suggested in Eq. Dibenzo Derivatives The halogenation of dibenzo derivatives of five- and six-membered heterocycles presents a rather clear orientation pattern.
The preference for substitution ortho and para to atoms having available electron pairs [e. Although similar orientation is observed with aza-aromatic systems under neutral P. However, for para and ortho attack at least contributing structures are avoided which place positive charge on the nitrogen atom In this regard phenazine also deserves special comment.
Only chlorination ortho to the central pyridazine ring has been reported. Although attack at either of the nonequivalent carbon atoms leads to some increase of positive charge on nitrogen, attack a t C-1 involves dispersal of positive character without disrupting the quinoxaline conjugation 28 and Systems Having Positive Poles For basic nitrogen heterocycles in strongly acidic media H2S04 or AIXs , halogenation will take place via a positively polarized heterocycle whose pyridinoid r-cloud is strongly depleted.
Localization energy calculations for protonated aza-aromatic systems by simple molecular orbital theory have permitted predictions of the sites of nitration which agree satisfactorily with experimental findingsg3 Table VI.
Halogenation of these heterocycles by the method of Derbyshire and Waters bromine and silver sulfate in concentrated sulfuric acid presents conditions quite comparable to those of nitration, and hence it is gratifying to note that almost equal proportions of the C-5 and C-8 isomers are obtained from both the nitration and the halogenation of quinoline. Hopefully future extension to other heterocycles will clarify the relation of this halogenation method to the many existing studies of heterocyclic nitration.
It can be noted that a qualitative localization treatment, similar to that applied to neutral heterocycles, is applicable t o protonated heterocycles with satisfactory results. Thus, the nitration and, presumably, the Derbyshire-Waters halogenation of quinoline, isoquinoline, quinoxaline, and cinnoline in the alpha positions of the benzenoid 97 J. Eisch and H. Gilman, Chern. EISCH ring simply reflects the deactivation of the heterocyclic ring and the greater stability of structures of type 30 over those of type 31 of.
The latter facet is intriguing not only in attaining a more intelligent control of preparative halogenation, but also in mapping the electronic response of extensively SEC. Special urgency exists for precise data on the isomer distribution and the relative reactivities of heterocycles toward various halogenating agents.
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Furthermore, tests of the reversibility and the role of catalysts in high-temperature halogenation deserve re-examination in the light of suggested explanations for the observed change in orientation. For halogenation in solution, the role of solvent polarity, the kinetic behavior of halogen-heterocycle adducts, the existence of kinetic isotope effects or of base catalysis, as well as the determination of halogenation rate laws, all stand in need of intensive study.
The harvest of electronic insight could be great, if the laborers are not few. The 1,2-DithioliumIon. Methods of Preparation. Chemical Properties. Physical Properties. The 1,3-DithioliumIon. Introduction The 1,2- and 1,3-dithiolium ions 1 and 2 are unsaturated fivemembered ring cations in which each of the two ring sulfur atoms can contribute a free pair of 3 p electrons to the mesomeric bond system.
This relationship is undoubtedly responsible for much of the intensive theoretical and experimental investigation currently being carried out on these systems. In Liittringhaus and Bottche?
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Hurtley and Smiles4 had isolated fused-ring derivatives of 2 as early as , but were understandably unable to find a satisfactory explanation for the valence relationships on the basis of the views held at that time. The parent compounds 1 and 2, however, were not synthesized until E. Klingsberga and D. Leaver et aL7 ,respectively. Most of the relevant papers on which this chapter is based were also published within the last 5 years. The objections to each of the possible names have already been discussed.
Zahradnik, Advan. Heterocyclic Chem. B6ttoher and A. Luttringhaus, Ann. Luttringhaus, Angew. Hurtley and S. Smiles, J. Wizinger and L. Soder, Chimia Aarau 12, 79 Klingsberg, Chem, Ind.
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