Position substitutable

As in the case of the free bases, the substitution of a nuclear hydrogen atom by a methyl group induces a bathochromic shift that decreases in the order of the position substituted 4->5->2- Ferre et al. (187) have proposed a theoretical model based on the PPP (tt) method using the fractional core charge approximation that reproduces quite correctly this Order of decreasing perturbation. 

Substituents with -I,+M effects such as halogen show a similar orientation effect to that of alkyl groups. If the substituent is in the 2-position, substitution occurs at C-5 if it is in position 3, substitution occurs preferentially at C-2 or if steric requirements of the group or electrophile intervene, then substitution occurs at C-5. 

Having its pyrazolic 4-position substituted, electrophilic attack on indazoles takes place in the 3-position and in the homocycle (the 5- and 7-positions). The condensation of a benzene ring results in a decrease of the aromaticity of the pyrazole moiety, as in naphthalene compared to benzene, and therefore basic ring cleavage is easier in indazoles than in pyrazoles (Section 4.04.2.1.7(v)). 

Radical chlorination reactions show a substantial polar effect. Positions substituted by electron-withdrawing groups are relatively unreactive toward chlorination, even though the substituents may be potentially capable of stabilizing the free-radical intermediate " ... 

Substitutions (number prior) Positions substituted Reaction position AH (kcal/mol) AS (cal/mol K)... 

If a substituted aromatic hydrocarbon is used, the ketone gioLip then enteis the paia-position, or, if this is occupied, the oitho-position. Substituted aromatic acid chlorides may. also be used, and if the acid is dibasic and has two caiboxyl chloiide gioups, two molecules of the aromatic hydiocaibon may be. attached. If phosgene is used with two molecules of benzene, benzophenone is obtained. 

Abnormal Hemoglobin Normal Residue and Position Substitution... 

It can be seen from resonance structures (2) to (4) that a — I — M-substituent deactivates the 3- and 5-position most strongly in electrophilic substitution. If this deactivation of the 5-position is strong enough to overcome the activating effects of the sulfur in the 5-position, substitution will be directed to the 4-position to an increasing extent. Tirouflet and Fournari studied the nitration of 2-substituted thiophenes of this type. The analysis was carried out polarographically, and the percentage of 4-isomer was as follows ... 

Halobenzenes undergo nucleophilic aromatic substitution through either of two mechanisms. If the halobenzene has a strongly electron-withdrawing substituent in the ortho or para position, substitution occurs by addition of a nucleophile to the ring, followed by elimination of halide from the intermediate anion. If the halobenzene is not activated by an electron-withdrawing substituent, substitution can occur by elimination of HX to give a benzyne, followed by addition of a nucleophile. 

With acetic acid as solvent 68 is still the major product (Scheme 32). The minor product (69) probably forms in preference to the 3,5-isomer because the quinoline free base is reacting the high yield of 68 can be rationalized in terms of a 1,4- or 1,2-addition product that is rapidly bromi-nated at C-3. The 6- and 8-positions substitute more slowly [62JCS283, 62JCS291 77HC(32-1)319]. Both the 6- and the 8-bromoquinolines were 3-brominated under neutral conditions (62JOC1318). 

With the method applied it is possible to take into account substitution effects both in the A and C monomers, as explained elsewhere (12). The substitution effect factor Kjj indicates the factor by wKTch the reaction rate between monomer I and any other monomer L is multiplied for each previous bond formed between monomers I and J (i.e. first-shell substitution effects (7)). For positive substitution effects Kjj is larger than 1, for negative effects it is smaller than 1. 

Abstract We briefly underline the relevance of TS-1 catalyst for industrial applications in mild oxidation reactions using hydrogen peroxide as oxidant and review the experimental works employed over last two decades for imderstanding the structme of the Ti centers in the bare TS-1 material. After an animated and controversial debate that has lasted in the literature until 1994, several works (reviewed here in depth) have definitively assessed that Ti atoms occupy framework positions substituting a Si atom and forming tetrahedral... 

The substitution of CO in 2 by PF3 was recently the subject of an intensive investigation [47], that was followed by a similar study of the Mn-homolog [55], The authors investigated the substitutions by means of GC-MS, GC-IR and 19F-NMR. Assuming the composition [Tc2(CO)x(PF3)(i0 X)], there are 77 possible stereoisomers of which 24 could be assigned unambiguously, especially for x= 1, 2, 3. As was expected from the higher rc-density in the axial positions, substitution at these two positions was found to be preferred. 

Data on the bioavailability of PCDDs are limited. It is known that PCDDs incorporated into wood as a result of chlorophenol (preservative) treatment are bioavailable. Swine and poultry using chlorophenol-treated wooden pens or litter have been found to be contaminated with PCDDs (NRCC 1981). Toxicities of individual PCDD isomers can vary by a factor of 1000 to 10,000 for isomers as closely related as 2,3,7,8-TCDD and 1,2,3,8-TCDD, or 1,2,3,7,8-penta-CDD and 1,2,4,7,8-penta-CDD (Rappe 1984). Isomers with the highest biological activity and acute toxicity have four to six chlorine atoms, and all lateral (i.e., 2,3,7, and 8) positions substituted with chlorine. On this basis, the most toxic PCDD isomers are 2,3,7,8-TCDD, 1,2,3,7,8-penta-CDD, 1,2,3,6,7,8-hexa-CDD, 1,2,3,7,8,9-hexa-CDD, and 1,2,3,4,7,8-hexa-CDD (Rappe 1984). Ishizuka et al. (1998) have assigned toxic equivalencies for various PCDDs, with 2,3,7,8-TCDD given a value of 1 (highest biological activity), followed by a value of 0.5 for 1,2,3,7,8-penta-CDD a value of 0.1 for three PCDD isomers (1,2,3,4,7,8-hexa-CDD, 1,2,3,4,7,8-hexa-CDD, 1,2,3,7,8,9-hexa-CDD), a value of 0.01 for 1,2,3,4,6,7,8-hepta-CDD and a value of 0.001 for 1,2,3,4,6,7,8,9-octa-CDD. 

Single-Position Substitution Analysis and High-Throughput Screening Analysis 204... 

There is a pronounced difference in biological and toxicological effects between different PCDD and PCDF isomers which is contradictory to the chemical and physical properties of these compounds discussed above. The isomers with the highest acute toxicity are 2,3,7,8-tetra-CDD, 1,2,3,7,8-penta-CDD, 1,2,3,, 7 8-, 1,2,3,6,7,8- and 1,2,3,7,8,9-hexa-CDD, 2,3,7,8-tetra-CDF, 1,2,3,7 8 and 2,3,, 7 8-penta-CDF and 2,3,U,6,7,8-hexa-CDF, see Figure 2. All these isomers have their four lateral positions substituted for chlorine, and they all have LD,-0 values in the range 1-100 yg/kg for the most sensitive animal species (15-17) The same isomers have been reported to have the highest biological potency (l8). 

It is assumed that the heterocyclic core structure is responsible for the appropriate orientation of the aromatic rings in space and finally for binding to the enzyme. A wide variety of heterocycles can serve as templates, i.e. pyrrole, thiazole, oxazole furane, furanone, imidazole, isoxazole, pyrimidine and thiophene, but at the moment pyrazole and cylopentenone seem to be the most appropriate for achieving COX-2 specificity. For optimal activity, one aromatic ring must be substituted with a methylsulfonyl or a sulfonamide substituent in the para position. Substitution at position 4 of one of the aromatic systems with a sulfonamide or a methylsulfonyl group is essential for COX inhibition. Replacement of the methylsulfonyl group by a sulfonamide group reduces COX-2 selectivity but improves oral bioavailability. 

Acetylation of alkyl-substituted thienothiophenes (71)-(75) followed the same pattern, the incoming acetyl function entering an unsubstituted a-position. / -Substitution occurred only in the cases where available a-positions were blocked. Under vigorous reaction conditions, diacetylation has been reported to occur. Representative examples are set forth in Schemes 19-23 <76AHC(19)123). 

PMR studies on 1,3,4-triazaindolizines substituted in 2-, 5-, 6-, or 7-positions show a connection between op and the proton shift relative to the 2- or 6-proton resonance in the unsubstituted compounds.403 The PMR chemical shift in the N-Me group of 5-substituted 2-chloro-l-methylbenzimidazoles correlates with az in CDC13 but with ap in MeCOOH demonstrating the reduction in through resonance on protonating the five-membered ring 404 there is, however, no correspondence of chemical shift produced by 6-substitution with am,404 nor is there any connection between 4-, 5-, 6-, or 7-positional substitution of... 

This class of reaction is called Friedel-Crafts alkylation in honor of its discoverers, C. Friedel (a French chemist) and J. M. Crafts (an American chemist). The metal-halide catalyst functions much as it does in halogenation reactions to provide a source of a positive substituting agent, which in this case is a carbocation ... 

While polar protic solvents, such as MeOH, strongly retard reaction,33 phase transfer catalysis using benzene34 or addition of crown ethers to potassium alkoxides in benzene33 allows reaction at 25 C. Even with strong electron donors, such as alkyl, methoxy or dialkylamino in the ortho, meta or para positions, substitution for chloride by potassium methoxide proceeds smoothly using the crown ether activation in benzene (equation 8).33... 

Note that the second term is always negative since both XA and XB are both less than one and the natural log of a number less than one is negative. AH may be either negative or positive so AG can also be either negative or positive. Substituting AHm = XAXBQ,... 

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