Reactivity of halogens

Regarding the substituent effect on reactivity of groups in positions 4 and 5 there is little information in the literature. The reactivity of halogen in position 5 seems to be increased when an amino group is present in position 2. Substitution products are easily obtained using neutral nucleophiles such as thiourea, thiophenols, and mercaptans (52-59). 

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. 

Enhanced reactivity of halogen atoms toward -nucleophiles... 

Perhaps the most straightforward approach to increasing the reactivity of halogenated substrates--polymeric or otherwise—is to exploit the well known order of leaving group ability, i.e.,... 

The reactivity of halogens can be explained by their AH° and Fact for each step ... 

Steric effects are undoubtedly a factor in the reactivity of halogen substituted fumaric acid complexes to Cr+2 (18). The results of rate measurements for these species are shown in Table III. Specific rates are entered both for the (H+) independent path (path 1, ki) and for the path first order in (H+) (path 2, fo). 

CPB801 75PHA134). In position 6 reactivity of halogens is as low as that in position 5 of pyrimidines even when activated by two adjacent groups they react with only a few reagents (61CPB814). 

The reactivity of halogens in such addition reactions decreases in the order chlorine) bromine])iodine. Usually chloro-and bromo-compounds are produced by this method ... 

The reactivity of halogen atoms in azines toward Sajj displacement is in line with the sequence discussed in Section 3.2.3.1.1. 

Reactivity increases in the diazines as compared with pyridines. 3-Chloropyridazine (910) and 2-chloropyrazine, for example, undergo the usual nucleophilic replacements (cf. Section 3.2.3.10.6.ii) rather more readily than does 2-chloropyridine. 2-, 4- and 6-Halogen atoms in pyrimidines are easily displaced. The reactivity of halogens in pyridazine 1-oxides toward nucleophilic substitution is in the sequence 5 > 3 > 6 > 4. 

The particular reactivity of halogens toward stannoles was demonstrated by Sandel and coworkers154. Treatment of 1,1-dimethyltetraphenylstannole with iodine trichloride led to cleavage products and the Hilckel aromatic 2,3,4,5-tetraphenyliodonium ion154 (equation 54). 

Many attempts have been made in the past to detect differences in reactivity of halogen atoms in 2Pi and 2Pj states but without much success. Indeed, until recently little was known about rates of transformation of one atomic state into another but some beautiful work by Donovan and Husain36 has provided some information on this point. Emission of infrared radiation as well as collisions may cause the reaction... 

Mixed-substituent polyphosphazenes are also accessible by utilizing the different reactivities of halogens according to their location in the polymer. For example, the chlorine atoms in the side groups of phosphazo polymers (3.5 and 3.6) are more reactive than those linked directly to the main chain hence, the side-group halogens react first,... 

As in halogens (see above), the reactivity of halogen fluorides (BrF3, BrF5) C1F3) in fluorination reactions could be significantly increased in the presence of protic or Lewis acids (85], For example, salt BrFJSbFg reacts with F-benzene even at -80 °C with the formation of F-cyclohexadiene-1,4 ... 

Reactivity of halogen fluorosulfates X0S02F (X=C1, Br, I) is very similar to that of halogen triflates however, all of them have higher thermal stability, and they are distillable liquids [8, 102]. The chemistry of halogen fluorosulfates, including addition to fluoroolefins, has been reviewed [8] here only a short summary of these reactions is given. 

The facile reaction of CAA and BAA with nucleosides and nucleotides is one example of many of the applications of the bifunctional reactivity of halogenated aldehydes and ketones in modification of biomolecules. In an early example of the extensive use of halogenated ketones as protease substrate analogues, l-V-tosylamido-2-phenylethyl chloro-methyl ketone (TPCK) 30 was synthesized as a chymotrypsin substrate analogue. Stoichiometric inhibition was accompanied by loss of one histidine residue as a result of alkylation by the chloromethyl moiety68. A host of similar analogues were subsequently prepared and used as selective enzyme inhibitors, in particular for the identification of amino acid residues located at enzyme active sites69. 

The reactivity of halogen compounds, of course, strongly depends on the halogen. Fluoroaliphatic compounds are nonreactive unless they contain another reactive functional group. Chloro-compounds are fairly reactive, k > 108 M 1 s 1, and their reactivity increases in the presence of neighbouring electron withdrawing groups. Bromo-and iodo-compounds are more reactive in that order. Thiols and disulphides are very reactive, whereas thiol anions and thioethers are only fairly reactive. Nitro- and nitroso-compounds are very reactive toward eaq. 

Plazek [28,28b] and Plazek and Talik [28a] stated recently that the reactivity of halogens in nitro derivatives of pyridine is much higher than in the similar benzene derivatives. Thus, at 20°C where only 0.5% of chloro-2,4-dinitrobenzene was subjected to nucleophilic displacement of chlorine by the amino group, the figure was 98.3% for 2-chloro-3,5-dinitropyridine. 

The reactivity of halogen atoms in position 2 of oxazoles is considerably enhanced by quaternization. This is best illustrated by the synthetic utility of the salt (141) which, like other Ar-alkyl-2-halogeno-azolium and -azinium salts, effects a number of condensation reactions but it far surpasses these other salts in activity (79AG(E)707). Thus it activates carboxylic acids and it dehydrates formamides to isocyanides (Scheme 6). Amides are similarly converted into cyanides, ketones (RCH2COAr) into alkynes (RC=CAr), and cyanohydrins (RCH(OH)CN) are transformed into the corresponding chloro compounds <79CL1117>. 

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