Electrophilic Halogenation Reactions

Wilkes and coworkers have investigated the chlorination of benzene in both acidic and basic chloroaluminate(iii) ionic liquids [65]. In the acidic ionic liquid [EMIMJCl-AlCh (X 0.5), the chlorination reaction initially gave chlorobenzene. 

The iodination of aromatic compounds using the electrophilic fluorinating agent l-(chloromethyl)-l,4-diazabicyclo[2,2,2]octane tetrafluoroborate and iodine was carried out in a range of [BF4] and [PFe] ionic liquids and generally gave high yidds [106]. Trihalide-based ionic liquids have been synthesised and the structure of the 

The bromination of aromatic compounds using N-bromosuednimide (NBS) occurs in high yield in ionic liquids such as dibutylimidazohum tetrafluoroborate [110]. The yields of the monobrominated product were all in the 80% to 98% range. NBS was also used in the Wohl-Ziegler Q -bromination of aryl methyl groups [111]. The reaction in [BMIM][PF6] typically gave a 5 to 10% improvement in the yield, compared with a solvent-free reaction. 

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B. D. de la Mare and R. Bolton Electrophilic Additions to Unsaturated Systems, 2nd ed., Elsevier, Amsterdam, 1981 P. B. D. de la Mare Electrophilic Halogenation, Reaction Pathways Involving Attack by Electrophilic Halogens on Unsaturated Compounds, Cambridge University Press, London, 1976. [78] F. Freeman Possible Criteria for Distinguishing between Cyclic and Acyclic Activated Complexes in Addition Reactions, Chem. Rev. 75, 439 (1975). [79] G. Heublein Neuere Aspekte der elektrophilen Halogenaddition an Olefine, Z. Chem. 9, 281 (1969). [80] R. S. Brown, Acc. Chem. Res. 30, 131 (1997). 

Scheme 12 Catalytic chlorination of azobenzene via the proposed Pd(II)/ Pd(IV) catalytic cycle. The first directing group-assisted electrophilic halogenation reaction...

You have just seen that cyclic halonmm ion intermediates are formed when sources of electrophilic halogen attack a double bond Likewise three membered oxygen containing rings are formed by the reaction of alkenes with sources of electrophilic oxygen... 

Reactions. The CF O— group exerts predominant para orientation in electrophilic substitution reactions such as nitration, halogenation, acylation, and alkylation (350). 

The halogenation reaction conditions can be chosen to direct attack to the methyl group (high temperature or light to form free-radicals) or the aromatic ring (dark, cold conditions with FeX present to form electrophilic conditions). 

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. 

Beyer synthesis, 2, 474 electrolytic oxidation, 2, 325 7r-electron density calculations, 2, 316 1-electron reduction, 2, 282, 283 electrophilic halogenation, 2, 49 electrophilic substitution, 2, 49 Emmert reaction, 2, 276 food preservative, 1,411 free radical acylation, 2, 298 free radical alkylation, 2, 45, 295 free radical amidation, 2, 299 free radical arylation, 2, 295 Friedel-Crafts reactions, 2, 208 Friedlander synthesis, 2, 70, 443 fluorination, 2, 199 halogenation, 2, 40 hydrogenation, 2, 45, 284-285, 327 hydrogen-deuterium exchange, 2, 196, 286 hydroxylation, 2, 325 iodination, 2, 202, 320 ionization constants, 2, 172 IR spectra, 2, 18 lithiation, 2, 267... 

With more electrophilic halogenated olefins, additions of tnfluoromethyl hypofluonte appear to go by radical processes [139] and give oligomeric products [140] or one-to-one adducts [141,142] (equation 4) depending on reaction conditions... 

OL Halogenation (Sections 18.2 and 18.3) Halogens react with aldehydes and ketones by substitution an a hydrogen is replaced by a halogen. Reaction occurs by electrophilic attack of the halogen on the carbon-carbon double bond of the enol form of the aldehyde or ketone. An acid catalyst increases the rate of enolization, which is the ratedetermining step. 

Diaza-l,6-dioxa-6<2-tellurapentalenes 97 do not undergo electrophilic substitution reactions such as halogenation, nitration, or Friedel-Krafts and Vilsmaier reactions (79BSF199). 

The presence of an TV-oxide group activates the 1,2,4-triazine ring toward electrophilic attack, for instance, in halogenation reactions. Thus, 3-methoxy- and 3-amino(alkylamino)-1,2,4-triazine 1-oxides 16 react easily with chlorine or bromine to form the corresponding 6-halo-1,2,4-triazine 1-oxides 17 (77JOC3498, 78JOC2514). 

Isoxazoles are known at present to undergo the following electrophilic substitution reactions nitration, sulfonation, halogenation, chloroalkylation, hydroxymethylation, and mercuration. Repeated attempts to effect the Friedel-Crafts reaction in the isoxazole series in the authors laboratory failed. The isoxazole nucleus seems not active enough to react with weak electrophilic reagents. 

As with other electrophilic substitution reactions, there is practically no work available on the halogenation of isoxazoles with functional substituents. The only instance that indicates that the general pattern holds true here is the extremely rapid bromination of 3-anilino-5-phenylisoxazole (65), in which the isoxazole ring is the first to react with 1 mole of bromine, yielding... 

Accordingly, they do not easily add to reagents such as halogens and acids as do alkenes. Aromatic hydrocarbons are susceptible, however, to electrophilic substitution reactions in presence of a catalyst. 

The hydroxyl group is a strongly activating, ortho- and para-directing substituent in electrophilic aromatic substitution reactions (Section 16.4). As a result, phenols are highly reactive substrates for electrophilic halogenation, nitration, sulfonation, and lTiedel-Crafts reactions. 

Both electrophilic and nucleophilic reactions can generate halogenopur-ines with differences in regioselectivity dependent on substituents and on the nature of the substrate (anion, neutral molecule, or cation). In the neutral molecule nucleophilic displacements occur in the order 2 > 4 > 6 in the anion the imidazole ring may be sufficiently 7r-excessive for attack to occur at C-2, and the nucleophilic substitution order becomes 4 > 6 > 2. Strong electron donors are usually necessary to promote 2-halogenation by electrophilic halogen sources. 

Although the simple mono-(2-,4-,6-, and 7-) and some di-(6,7-, 2,4-) tri-(2,4,6-, 2,4,7-), and tetra-(2,4,6,7-) -chloro derivatives are known, they are often unstable and highly susceptible to nucleophilic attack, and little is known about some of the compounds (64JCS1666 84MI10). No electrophilic halogenations have yet been reported, but there have been a few instances of chlorine introduction by Meisenheimer reaction of pteridine N-oxides (78JOC680 82LA2135). 

The second paper22 dealt with model reactions and showed that many side reactions occurred between halogens and the other reagents used and experiments had to be designed to minimize these reactions. Using 2,4,4-trimethyl-l-pentene, the authors showed that initiation was due to electrophilic halogen. 

In vanadium-dependent haloperoxidases, the metal center is coordinated to the imidazole system of a histidine residue, which is similarly responsible for creating hypochlorite or hypobromite as electrophilic halogenating species [274]. Remarkably, a representative of this enzyme class is capable of performing stereoselective incorporation of halides, as has been reported for the conversion of nerolidol to various snyderols. The overall reaction commences through a bromonium intermediate, which cyclizes in an intramolecular process the resulting carbocation can ultimately be trapped upon elimination to three snyderols (Scheme 9.37) [275]. 

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