Peri-position

From the standpoint of geometrical considerations, the major difference is in the far greater steric requirements of the nitro group. This could result in either primary or secondary steric effects. Nevertheless, primary steric effects do not seem to be necessarily distinguishable by direct kinetic comparison. A classic example is the puzzling similarity of the activation parameters of 2-chloropyrimidine and 2,6-dinitrochlorobenzene (reaction with piperidine in ethanol), which has been described by Chapman and Rees as fortuitous. However, that nitro groups do cause (retarding) primary steric effects has been neatly shown at peri positions in the reaction with alkoxides (see Section IV,C, l,c). 

All products were identified and followed by GC/MS. The lateral positions (C-2, C-3) of 1,2,3,4-TBDD are slightly more reactive compared to the peri positions (C-1, C-4) the two Br3Cl-isomers appear in a ratio of approximately 1 1,5. The relative rate constants of 5 aromatic bromine compounds were determined (Table 3). 

The debromination/hydrogenation reaction shows some stereospecificity. Bromine in lateral positions of C-2, C-3, C-6 and C-7 reacts faster than in the peri position (C-1, C-4, C-5, C-8). This is shown below for photolysis of 1,2,3,4,6,7-hexabromodibenzodioxin. 

The antibacterial agent flumequine 280 was synthetized in optically active form by starting with resolution of the two enantiomers of a suitably substituted racemic tetrahydroquinoline through formation of the (lf )-3-bromocamphor-8-sulfonates. After N-alkylation of the (2K)-tetrahydroisoquinoline enantiomer 277 with diethyl ethoxymethylene-malonate to give 278, the quinolizidine system 279 was formed by acylation onto the peri-position. This compound was finally hydrolyzed to afford 280 (Scheme 60) <1999TA1079>. 

The intermolecular cyclization that involves the peri positions of unsubstituted systems (6 6) has been applied to the construction of fused (6 6 6) systems. An example of this approach is the reaction of bicyclic guanidine 123 with 1,3-dibromopropane furnishing the /wi-fused product 124 which can be isolated as tetrafluoroborate salt (Equation 12) C1996CB21, 1997TL1911>. 

In contrast, the fluorine atom at the peri-position of 12F-5-methylchrysene influences dihydrodiol formation in the adjacent angular ring. Whereas the ratio of 5-MeC-7,8-diol to 5-MeC-l,2-diol in mouse epidermis was 1 1, 2 hr after topical application of [%] 5-MeC, the ratio of 12F-5-methylchrysene-7,8-diol to 12F-5-methylchrysene-1,2-diol was 68 1. In contrast to 5-MeC, the metabolites formed from 12F-5-methylchrysene in mouse skin resulted almost exclusively from oxidation at the 7,8-bond (57). Thus, metabolic switching to the less tumorigenic 7,8-dihydrodiol appears to be the basis for the lower tumorigenicity of 12F-5-methylchrysene compared to 5-MeC. 

While carbene lp is completely stable towards irradiation with visible or UV light, carbenes lq and lr bearing methyl groups in the peri-position adjacent to the carbene center slowly rearrange on irradiation with k > 420 nm." During this photolysis the color of the matrix changes from yellow (carbene) to purple. By comparison of the experimental with the DFT-calculated IR spectrum the purple compound was identified as 5-methylene-5//-anthracenc-1 -one (23) with an extended rr-system that is responsible for the intense color. 

The palladium-catalyzed arylation of 2-phenylphenols and naphthols shows an interesting feature of arylation of C-H bonds, leading to the formation of an (aryl)(aryloxy)palladium(n) intermediate.65,65a,65b The phenolates are suitable as precoordinating groups. The reaction of 2-hydroxybiphenyl with an excess of iodobenzene occurs regioselectively at the two ortho-positions of phenyl group under palladium catalysis (Equation (57)). In the case of 1-naphthol, the peri-position is phenylated (Equation (58)). 

In a bidentate ligand system, three molecules of a dye containing either a terminal salicylic acid unit (as in 5.2) or an o-nitrosonaphthol residue are able to chelate simultaneously with a trivalent metal ion of CN6, such as chromium (III) or iron(III), to form a 1 3 metal-dye complex (as in 5.8). Historically, the most important bidentate ligand system was alizarin (5.1). It has been suggested that both hydroxy groups and the keto group in the peri position are all involved with the metal atom in the chelation mechanism. 

A number of bases, with pyridine heading the list, act as proton acceptors in the electrophilic coupling reaction. Their contribution is particularly useful if voluminous substituents exist in ortho or peri position relative to the coupling location of the intermediate they may also facilitate coupling with diazonium ions of low electrophilicity (e.g., diazophenols). 

Establishing that a smaller substituent in the peri position can raise the barrier, Oki and co-workers (149) were interested in finding the peri substituent effect on the barrier to rotation, and prepared a series of 9-(l,l-dimethyl-2-phenyl-ethyl)triptycenes (104). Data in Table 22 indicate that the barrier to rotation... 

Since, in the case of the tm-butyltriptycene skeleton, the maximum barrier to rotation is realized when the substituent in the peri position is medium sized, it was of interest to see whether a similar result would be obtained with other tertiary alkyl groups. Thus to complete the series, 1,2,3,4-tetrafluoro- and l,4-dimethoxy-9-(l-cyano-l-methylethyl)triptycenes (103, X = Y = F or X = CH30, Y = H) were prepared. The fine energies of activation for rotation of the fluoro and the methoxy compounds were 39.9 and 38.9 kcal/mol, respectively, at 462 K (152). It may be too early to draw a general conclusion in the tertiary alkyl series, but it is tempting to consider that the highest barriers are obtained when the peri substituent in this series is fluorine. 

So far triptycenes carrying a secondary alkyl group in the 9-position have been found to give rather unstable atropisomers. To raise the barrier to rotation of the sec-alkyl group, the introduction of substituents in more than one peri position may be helpful the same is true when there is a primary alkyl group at the 9-position (vide infra). 

Summarizing the results related to the barriers to rotation of a secondary alkyl group in the 9-position of a 1-substituted triptycene, we note that the maximum barrier is realized when the peri substituent is chlorine or bromine. Evidently the size of the substituent that gives the maximum barrier to rotation is shifted from that in the 9-rm-alkyl systems. This is considered to be a reflection of the strain in the ground state, which is usually larger in the tertiary alkyl systems than in the secondary, if the same substituent is present in the peri position. 

From the trend in barriers of tertiary and secondary alkyl groups attached to the 9-triptycyl group, the barrier to rotation about a C(9)—C(CH2) bond in 9-ben-zyltriptycenes (116) that carry a peri substituent is expected to be still lower, and it is only about 12 kcal/mol (165). However, if substituents are introduced at another peri position, the barriers are raised considerably. 1,2,3,4,5,6,7,8-... 

A different behavior is exhibited by naphthalene-1,8-dicarbocal-dehyde (73). No m-naphthane derivatives are obtained on reaction with nitromethane, nitroethane or other methylene components. The basic medium, required for aldol type additions, causes the dialdehyde to undergo Cannizzaro reaction to the naphthopyranon (74) via an intramolecular 1,5-hydride shift, which is sterically favoured by the peri-position of the two aldehyde functions 28). 

Methoxynaphthalenes may be lithiated in their ortho or peri positions according to conditions (see Table 1 in Section LA). 1,4-Dimethoxynaphthalene, for example, perilithi-ates cleanly with f-BuLi (Scheme 67) ... 

---