Bond fixation

Proton-proton coupling constants of benzo rings of benzazoles can illuminate the bonding in such compounds. Thus, comparison of the J values for naphthalene with those for benzotriazoles of different types (Table 13) shows evidence of bond fixation, particularly in the 2-methyl derivative (98) (71PMH(4)l2l). 

A multiply bonded nitrogen atom deactivates carbon atoms a or y to it toward electrophilic attack thus initial substitution in 1,2- and 1,3-dihetero compounds should be as shown in structures (110) and (111). Pyrazoles (110 Z = NH), isoxazoles (110 Z = 0), isothiazoles (110 Z = S), imidazoles (111 Z = NH, tautomerism can make the 4- and 5-positions equivalent) and thiazoles (111 Z = S) do indeed undergo electrophilic substitution as expected. Little is known of the electrophilic substitution reactions of oxazoles (111 Z = O) and compounds containing three or more heteroatoms in one ring. Deactivation of the 4-position in 1,3-dihetero compounds (111) is less effective because of considerable double bond fixation (cf. Sections 4.01.3.2.1 and 4.02.3.1.7), and if the 5-position of imidazoles or thiazoles is blocked, substitution can occur in the 4-position (112). 

Substituents in the 4-position of these compounds are also a to a multiply-bonded nitrogen atom, but because of bond fixation they are relatively little influenced by this nitrogen atom even when it is quaternized (333). This is similar to the situation for 3-substituents in isoquinolines, cf. Chapter 2.02. In general, substituents in the 4- and 5-positions of imidazoles, thiazoles and oxazoles show much the same reactivity of the same substituents on benzeneoid compounds (but see Section 4.02.3.9.1). 

A heterocyclic ring induces partial double-bond fixation in a fused benzene ring. Hence, for example, diazo coupling occurs at the 7-position of 6-hydroxyindazole (349), and Claisen rearrangement of 6-allyloxy-2-methylbenzothiazole (350) gives the 7- and 5-allyl products in a ratio of 20 1. 

The seeond problem is the relationship between the position of the substituent in the pyrazole nueleus and its mobility. In the 1-phenylpyrazole series in their reaetions with Grignard reagents, the bromine reaetivity deereases in the order 5-Br>4-Br>3-Br (B-76MI40402). When an eleetron-withdrawing group is present at the 4-position, the 5-ehloropyrazole is more reaetive than 3-ehloropyrazole, but this has been attributed to bond fixation (Seetion 4.02.3.9). Thus, this problem needs further elarifieation. 

Table 7 also indicates that the rate enhancements for a 3- and 5-methyl group vary significantly among 1,2-azoles. The difference between the increments in log units for a 3-and 5-methyl group, which should vary directly with bond fixation in the ground state, is larger for isoxazole (1.4) than for pyrazole (0.7) and for isothiazole (0.2). This indicates that the aromaticity increases in the same order and contributes the first quantitative evidence that the 1,2-azoles follow the same aromaticity order as furan < pyrrole < thiophene. 

Isothiazole-4,5-dicarboxylic acid, 3-phenyl-dimethyl ester synthesis, S, 150 Isothiazole-5-glyoxylic acid ethyl ester reduction, 6, 156 Isothiazole-4-mercurioacetate reactions, 6, 164 Isothiazole-5-mercurioacetate reactions, 6, 164 Isothiazoles, 6, I3I-I75 acidity, 6, 141 alkylation, 6, 148 aromaticity, S, 32 6, 144-145 basicity, 6, I4I biological activity, 6, 175 boiling points, 6, I43-I44, 144 bond fixation, 6, 145 bond orders, 6, I32-I34 calculated, 6, 133 bromination, S, 58 6, 147 charge densities, 6, 132-134 cycloaddition reactions, 6, 152 desulfurization, S, 75 6, 152 deuteration, S, 70... 

The irregularity in the bond lengths of naphthalene in the ground state (misleadingly called bond fixation) has been used to explain the poor transmission of resonance activation in 2,3-orienta-... 

Using the above procedure and the A j, values, Binsch has examined the second-order bond fixations in the ground states of linear, cyclic, and benzenoid hydrocarbons and nonalternant hydrocarbons... 

On the other hand, in cata-condensed nonalternant hydrocarbons IV, VI, X and XI, peri-condensed nonalternant hydrocarbons XIV — XVIII, fulvenes XIX and XX, and fulvalenes XXI—XXIII, self-consistency was achieved only for the fully-symmetrical nuclear arrangement. All these molecule, except azulene pCl), also show in a greater or lesser degree a pronounced double-bond fixation. 

The s-indacene (III) synthesized by Hafner s group and its 7-membered analogue (IX) are predicted to assume a skewed structure with a moderate double-bond fixation. As for (III), this conclusion supports the previous theoretical works and is in accordance with the experimental information. 

For molecules XVI —XVIII it is predicted that bond lengths of the naphthalene core are almost the same as those of the free naphthalene molecule, and in the other region of the molecule marked bond fixations are observed . The most stable ground-state geometry of XVI corresponds to the aromatic model proposed by Lo and Whitehead . Molecules XVI and XVII have been synthesized by Trost and Bright and Boekelheide and Vick , respectively. The present results are in good qualitative agreement with the available experimental information. 

The calculated bond lengths for the 2 structure of the anion radical of heptafulvalene shown in Fig. 7 indicate that in one of the ring there exists a significant bond fixation to the same extent as that in the neutral heptafulvalene, while in the other ring bond lengths are nearly equalized. The calculated spin densities, presented in Table 3, indicate that the unpaired spin is localized essentially on the latter ring. 

The cation radical heptafulvalene, on the other hand, undergoes no symmetry reduction. Both the rings show a moderate double-bond fixation (Fig. 7), and the unpaired spin is delocalized throughout the molecule (Table 3). 

Inspection of Fig. 7 reveals that in the cation radical of XXI a marked bond fixation exists in one of the rings, while bond lengths are nearly equalized in the other ring, on which the unpaired spin is delocalized (Table 3). On the other hand, in the anion radical of XXI, there is a moderate bond fixation in both rings, and the unpaired spin is delocalized over the entire molecule. 

For molecules I, III and VII, Table 4 also gives theoretical values corresponding to the fully-symmetrical equilibrium structures. It will be seen that double-bond fixation brings about a considerable decrease in paramagnetic susceptibility. Partial evidence for such reduced mag-... 

The results of our calculations based on both the static and dynamic theories show that most of the nonbenzenoid cyclic conjugated systems examined exhibit in a greater or lesser degree a marked double-bond fixation. The static theory indicates that even in benzene there exists a hidden tendency to distort into a skewed structure and that such a tendency is actually realized in [4n-f-2] annulenes larger than a certain critical size. In nonalternant hydrocarbons bond distortion is a rather common phenomenon. Fulvenes, fulvalenes and certain peri-condensed nonalternant hydrocarbons undergo a first-order bond distortion, and... 

Addition of carbenes to Jt-electron excessive aromatic compounds, or those which possess a high degree of bond fixation, is well established. Dihalocarbenes react with naphthalenes with ring expansion to produce benztropylium systems (Scheme 7.8). Loss of hydrogen halide from the initially formed product leads to an alkene which reacts with a second equivalent of the carbene to yield the spirocyclopropyl derivatives in high yield (>95%) [14, 50]. Insertion into the alkyl side chain (see Section 7.2) also occurs, but to a lesser extent [14]. Not unexpectedly, dichlorocarbene adds to phenanthrenes across the 9,10-bond [9, 10, 14], but it is remarkable that the three possible isomeric spiro compounds could be isolated (in an overall yield of 0.05% ) from the corresponding reaction with toluene [14]. 

The combination of mesomeric electron-donating effects of the methoxy groups and the high bond fixation of the system results in high reactivity of 1-methoxy- and 1,2-dimethoxybiphenylene [28, 63] with dichlorocarbene to produce a complex mixture of ring-expanded products (Scheme 7.9). 

Polycyclic arenes having a high degree of bond fixation undergo epoxidation when exposed to tetra-alkylammonium hypochlorites over a pH range of ca. 8-9 [13] phenathridine is oxidized to phenanthridine. 

The consequences of the distortion of the aromatic benzene ring by fusion to a cyclopropene, as it occurs in cycloproparenes, has been the subject of much discussion and speculation. Much of this debate concerned the question of bond fixation in strained aromatics which has a long historical background. In 1930 Mills and Nixon observed different reactivities towards electrophilic substitution of the a and positions in tetralin (251) and indane (252). This observation was... 

The manifestation of a Mills-Nixon effect in benzocyclopropene (1) was examined by a variety of methods. Thus examination of the PE spectra of cyclo-proparenes and appropriate model compounds provided no information on the question.Similarly, NMR investigations using vicinal coupling constants or orthobenzylic coupling constants, involving methyl-substituted cydoproparenes revealed no evidence for sterically induced bond fixation. Theoretical calculations led to contradictory results. Early extended Hiickel calculations supported the concept in indanes but in the opposite sense than that suggested by Mills and Nixon. Semiempirical calculations for benzocyclopropene favored structure 258 over A substantial Mills-Nixon effect in the same direction resulted from... 

The X-ray structure of the cyclobutabenzocyclopropenes 84, 85 shows that fusion of an additional strained ring to the cycloproparene does not lead to more pronounced bond fixation, but results overall in a slightly enlarged benzocyclo-propene structure. In particular, all bonds of 84 are longer than the corresponding bonds of 1. ... 

The Mills-Nixon hypothesis that small ring annelation on benzene would induce bond fixation (bond alternation) by trapping out one Kekul6 tautomer is a casualty of early twentieth century structural chemistry. Due to a lack of direct methods for analyzing molecular structure, structural postulates of that time were often supported by an analysis of product distributions. An experimental observable such as product selectivity or isomer count was correlated to an unobservable structural feature derived on the basis of a chemical model. Classical successes of this method are van t Hoff s proof of the tetrahedral carbon atom and Fischer s proof for the configuration of sugars. In the case of Mills and Nixon, however, the paradigm broke down. 

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