Halogens chlorine atom

In the absence of catalysts, toluene when treated with chlorine (or bromine) at the boiling point, preferably with exposure to sunlight or other bright light source, undergoes halogenation in the side chain. The entrance of the first chlorine atom, for example, proceeds at a much faster rate than the entrance of the second chlorine atom so that in practice the major portion of the toluene is converted into benzyl chloride before appreciable chlorination of benzyl chloride occurs ... 

Partial mass spectra showing the isotope patterns in the molecular ion regions for ions containing carbon and (a) only one chlorine atom, (b) only one bromine atom, and (c) one chlorine and one bromine atom. The isotope patterns are quite different from each other. Note how the halogen isotope ratios appear very clearly as 3 1 for chlorine in (a), 1 1 for bromine in (b), and 3 4 1 for chlorine and bromine in (c). If the numbers of halogens were not known, the pattern could be used in a reverse sense to decide their number. 

This cycle is terrninated by the reaction of chlorine atoms with methane Cl + CH — HCl + CH3. The importance of this cycle depends on the avadabiLity of oxygen atoms and varies with altitude as well as the time of year it accounts for only 5% of the halogen-controUed loss at 15 km, but increases to 25% at 21 km. 

Aromatic compounds may be chlorinated with chlorine in the presence of a catalyst such as iron, ferric chloride, or other Lewis acids. The halogenation reaction involves electrophilic displacement of the aromatic hydrogen by halogen. Introduction of a second chlorine atom into the monochloro aromatic stmcture leads to ortho and para substitution. The presence of a Lewis acid favors polarization of the chlorine molecule, thereby increasing its electrophilic character. Because the polarization does not lead to complete ionization, the reaction should be represented as shown in equation 26. 

At least two catalytic processes have been used to purify halogenated streams. Both utilize fluidized beds of probably noimoble metal catalyst particles. One has been estimated to oxidize >9000 t/yr of chlorinated wastes from a vinyl chloride monomer plant (45). Several companies have commercialized catalysts which are reported to resist deactivation from a wider range of halogens. These newer catalysts may allow the required operating temperatures to be reduced, and stiU convert over 95% of the halocarbon, such as trichlorethylene, from an exhaust stream. Conversions of C-1 chlorocarbons utilizing an Englehardt HDC catalyst are shown in Figure 8. For this system, as the number of chlorine atoms increases, the temperatures required for destmction decreases. 

The reactivity of halogens in pyridazine N- oxides towards nucleophilic substitution is in the order 5 > 3 > 6 > 4. This is supported by kinetic studies of the reaction between the corresponding chloropyridazine 1-oxides and piperidine. In general, the chlorine atoms in pyridazine A-oxides undergo replacement with alkoxy, aryloxy, piperidino, hydrazino, azido, hydroxylamino, mercapto, alkylmercapto, methylsulfonyl and other groups. 

In the case of substituted phenazine fV-oxides some activation of substituents towards nucleophilic substitution is observed. 1-Chlorophenazine is usually very resistant to nucleophilic displacements, but the 2-isomer is more reactive and the halogen may be displaced with a number of nucleophiles. 1-Chlorophenazine 5-oxide (56), however, is comparable in its reactivity with 2-chlorophenazine and the chlorine atom is readily displaced in nucleophilic substitution reactions. 2-Chlorophenazine 5,10-dioxide (57) and 2-chlorophenazine 5-oxide both show enhanced reactivity relative to 2-chlorophenazine itself. On the basis of these observations, similar activation of 5- or 6-haloquinoxaline fV-oxides should be observed but little information is available at the present time. 

Dihaloquinoxalines are extremely reactive and both halogen atoms are replaceable, on occasions explosively (59RTC5), whereas in the case of dihalopyrazines, and tri- or tetra-halopyrazines, there is frequently a considerable difference in reactivity of the halogen atoms. When 2,3-dichloropyrazine is treated with ammonia at 130 °C, only one chlorine atom is displaced, giving 2-amino-3-chloropyrazine (66FES799). 

Important differences are seen when the reactions of the other halogens are compared to bromination. In the case of chlorination, although the same chain mechanism is operative as for bromination, there is a key difference in the greatly diminished selectivity of the chlorination. For example, the pri sec selectivity in 2,3-dimethylbutane for chlorination is 1 3.6 in typical solvents. Because of the greater reactivity of the chlorine atom, abstractions of primary, secondary, and tertiary hydrogens are all exothermic. As a result of this exothermicity, the stability of the product radical has less influence on the activation energy. In terms of Hammond s postulate (Section 4.4.2), the transition state would be expected to be more reactant-like. As an example of the low selectivity, ethylbenzene is chlorinated at both the methyl and the methylene positions, despite the much greater stability of the benzyl radical ... 

The halogen atom in benz-chloro substituted quinazolines is very stable (as in chlorobenzene), whereas the halogen atoms in positions 2 and 4 show the enhanced reactivity observed with halogen atoms on carbon atoms placed a and y to heterocyclic ring nitrogens. The chlorine atom in position 4 is more reactive than in position 2, and this property has been used to introduce two different substituents in the pyrimidine ring. ... 

Table 6-VI lists some properties of the halogens. In the elemental state, the halogens form stable diatomic molecules. This stability is indicated by the fact that it takes extremely high temperatures to disrupt halogen molecules to form the monatomic species. For example, it is known that the chlorine near the surface of the sun, at a temperature near 6000°C, is present as a gas consisting of single chlorine atoms. At more normal temperatures, chlorine atoms react with each other to form molecules ...

Apparently the diatomic molecules of the halogens already have achieved some of the stability characteristic of the inert gas electron arrangement. How is this possible How could one chlorine atom satisfy its need for one more electron (so it can reach the argon stability) by... 

There is no reason to believe that the off-diagonal Q integrals which yield this increase in U over I should be equal for longitudinal and transverse polarization but neither is there at present any basis for selecting different values. Hence we assume U1 = U2 and by use of the a values given above for the chlorine atom, the value of —El is calculated to be about 30 per cent smaller than was obtained in Table VI. Since the effect of anisotropy would be expected to be about the same for all of the halogens, the qualitative conclusions drawn from the results in Table VI are not affected. It is clear that anisotropy may be important, however, and must be considered in quantitative work. 

In a chain reaction, the step that determines what the product will be is most often an abstraction step. What is abstracted by a free radical is almost never a tetra- or tervalent atom (except in strained systems, see p. 989) and seldom a divalent one. Nearly always it is univalent, and so, for organic compounds, it is hydrogen or halogen. For example, a reaction between a chlorine atom and ethane gives an ethyl radical, not a hydrogen atom ... 

Halogens are named as substituents in the following way fluoro, chloro, bromo, and iodo. Essentially, we add the letter 0 at the end to say that they are substituents. If there are multiple substituents of the same kind (for example, if there are five chlorine atoms in fhe compound), we use fhe same prefixes fhaf we used earlier when classifying fhe number of double and friple bonds ... 

Finally, derivatives of the endogenous compound 2-octyl- y-bromoacetate (65) have been reported as FAAH inhibitors [79]. In a limited SAR study, it was found that replacement of the bromine with a chlorine atom had little effect on affinity. The replacement of the alkyl chain with oleyl-chain mimics resulted in an increase of affinity for FAAH (approximately 5-fold). The removal of the halogen and replacement with either a proton or methyl resulted in inactive compounds. The most potent compound identified in this series was compound (66) with an IC50 value of 0.6/rM [79]. 

Entries 7 and 8 illustrate conversion of diazonium salts to phenols. Entries 9 and 10 use the traditional conditions for the Sandmeyer reaction. Entry 11 is a Sandmeyer reaction under in situ diazotization conditions, whereas Entry 12 involves halogen atom transfer from solvent. Entry 13 is an example of formation of an aryl iodide. Entries 14 and 15 are Schiemann reactions. The reaction in Entry 16 was used to introduce a chlorine substituent on vancomycin. Of several procedures investigated, the CuCl-CuCl2 catalysis of chlorine atom transfer form CC14 proved to be the best. The diazonium salt was isolated as the tetrafluoroborate after in situ diazotization. Entries 17 and 18 show procedures for introducing cyano and azido groups, respectively. 

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