Hydroxyl group halogenation

Hydroxyl groups take precedence over ( outrank ) alkyl groups and halogen substituents m determining the direction m which a carbon chain is numbered The OH group is assumed to be attached to C 1 of a cyclic alcohol and is not numbered... 

The reaction of an alcohol with a hydrogen halide is a substitution A halogen usually chlorine or bromine replaces a hydroxyl group as a substituent on carbon Calling the reaction a substitution tells us the relationship between the organic reactant and its prod uct but does not reveal the mechanism In developing a mechanistic picture for a par ticular reaction we combine some basic principles of chemical reactivity with experi mental observations to deduce the most likely sequence of steps... 

Selectivity is not an issue m the conversion of alcohols to alkyl halides Except for certain limitations to be discussed m Section 8 15 the location of the halogen sub stituent m the product corresponds to that of the hydroxyl group m the starting alcohol... 

In aqueous solution chlorine and bromine react with alkenes to form vicinal halohy drins, compounds that have a halogen and a hydroxyl group on adjacent carbons... 

Anti addition occurs The halogen and the hydroxyl group add to opposite faces of the double bond... 

Like hydroxyl groups and ammo groups however halogen substituents possess unshared electron pairs that can be donated to a positively charged carbon This electron donation into the TT system stabilizes the intermediates derived from ortho and from para attack... 

Both parts of the Lapworth mechanism enol formation and enol halogenation are new to us Let s examine them m reverse order We can understand enol halogenation by analogy to halogen addition to alkenes An enol is a very reactive kind of alkene Its carbon-carbon double bond bears an electron releasing hydroxyl group which makes it electron rich and activates it toward attack by electrophiles... 

Halogenation Bromination and chlorination of phenols occur readily even in the absence of a cata lyst Substitution occurs primarily at the position para to the hydroxyl group When the para position IS blocked ortho substitution is observed... 

Halohydrin (Section 6 17) A compound that contains both a halogen atom and a hydroxyl group The term is most often used for compounds in which the halogen and the hydroxyl group are on adjacent atoms vicinal halohydrins) The most commonly encountered halohydrins are chlorohydnns and brornohydrins... 

The 5-position of quinolones can be substituted by small groups such as halogens, hydroxyl, or amino (54—56). The amino group at this position can be advantageous, particularly when appHed to 6,8-difluoro-7-piperazinyl or 6,8-difluoro-7-pyrrohdinyl quinolones. In contrast to 6,8-difluoro quinolones, when this replacement is appHed to ofloxacin, the resulting derivative has reduced antibacterial activity (57). Replacement of the 5-amino group with methylamine or dimethylamine causes activity to drop substantially. Sparfloxacin [110871-86-8] (21), a representative of 5-amino-6,8-difluoro quinolones, affords modest improvements in gram-positive activity as well as increased in vivo potency when compared with both ciprofloxacin and ofloxacin (54). 

Displacement of the hydroxyl group is exemplified by the production of isopropyl haUdes, eg, isopropyl bromide [75-26-3] by refluxing isopropyl alcohol with a halogen acid, eg, hydrobromic acid [10035-10-6] (12). 

Halogenation. Normally, 2-halopropane derivatives are prepared from isopropyl alcohol most economically by reaction with the corresponding acid haUde. However, under appropriate conditions, other reagents, eg, phosphoms haUdes and elemental halogen, also react by replacement of the hydroxyl group to give the haUde (46). 

Sulfonate Esters. Sucrose sulfonates are valuable intermediates for the synthesis of epoxides and derivatives containing halogens, nitrogen, and sulfur. In addition, the sulfonation reaction has been used to determine the relative reactivity of the hydroxyl groups in sucrose. The general order of reactivity in sucrose toward the esterification reaction is OH-6 OH-6 > OH-1 > HO-2. 

Direct halogenation of sucrose has also been achieved using a combination of DMF—methanesulfonyl chloride (88), sulfuryl chloride—pyridine (89), carbon tetrachloride—triphenylphosphine—pyridine (90), and thionyl chloride—pyridine—1,1,2-trichloroethane (91). Treatment of sucrose with carbon tetrachloride—triphenylphosphine—pyridine at 70°C for 2 h gave 6,6 -dichloro-6,6 -dideoxysucrose in 92% yield. The greater reactivity of the 6 and 6 primary hydroxyl groups has been associated with a bulky halogenating complex formed from triphenylphosphine dihaUde ((CgH )2P=CX2) and pyridine (90). 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

The hydroxyl groups of 5-hydroxypyrazoles (498) are readily replaced by halogens by the action of phosphorus halides. 

A further example employing displacement of a suitably activated hydroxyl group rather than halogen is also shown in Scheme 10. The use of titanium trichloride in the final step... 

This compound is also described as diethanol-p-toluidine in the older literature. Anilines bearing hydroxyl groups are preferred because they are less volatile than anilines without polar substituents. Tertiary aromatic amines with para-halogen substitution have also been reported for use in adhesives [42]. 

These xylylene groups are typically available commercially , by halogenation of xylenes ", by halomethylation of an aromatic" or by conversion of a diester into its corresponding diol followed by halogen-hydroxyl interconversion . 

Jsomerides of Morphine and Codeine. When morphine is treated with thionyl chloride, phosphorus trichloride or tribromide, the alcoholic hydroxyl group is replaced by the halogen, forming a-chloromorphide and bromomorphide respectively. The former on treatment with concentrated hydrochloric acid is converted into /3-chloromorphide. Schopf and Hirsch have provided evidence that the two are structural isomerides. With the same reagents codeine yields a parallel set of compounds, viz., a- and -chlorocodides, and bromocodide. The chief characteristics of these products may be summarised thus —... 

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