Triphenylphosphine halogenation

Bromonaphthalene has been prepared from 2-aminonaphtha-lene by the reaction of mercuric bromide with the diazonaphtha-lene. The reaction described in this preparation appears to be fairly general and provides a useful alternative method for introducing bromine into the aromatic nucleus. Using conditions similar to those outlined, the following have been prepared from the corresponding aryl alcohols a-bromonaphthalene (72%), 3-bromopyridine (76%), 2-bromopyridine (61%), 8-bro-moquinoline (48)%, o-bromotoluene (72%), />-chlorobromo-benzene (90%), -nitrobromobenzene (60%), and />-methoxy-bromobenzene (59%). The use of the triphenylphosphine-halogen complex to convert alcohols to alkylhalides is described elsewhere in this series. ... 

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). 

Halogens add to the double bond of the alcohol to afford the corresponding dihalo derivatives, eg, CgH CHXCHXCH20H, where X = Cl or Br. The allyHc chloride C H Cl [2687-12-9] can be obtained by treatment of the alcohol with hydrochloric acid, thionyl chloride, or carbon tetrachloride—triphenylphosphine as the halogen donor. 

A halogenating system related to the preceding case is formed by the reaction of triphenylphosphine with molecular bromine or chlorine. The system is not as sensitive to moisture as the phosphine-carbon tetrahalide system (see preceding section), but it suffers from the disadvantage that hydrohalic acids are produced as the reaction proceeds. Nevertheless, sensitive compounds can be successfully halogenated by the system, as exemplified by the preparation of cinnamyl bromide from the alcohol. 

Like tellurophene the fused compound forms 1,1-addition products with halogens (73BSF2468), but further bromination of such a 1,1-dibromo species gave 1,1,2-tribromobenzo[/>]tellurophene, which was able to be reduced to 2-bromobenzo[b]tellurophene. The 3-chloro and -bromo compounds were isolated following reaction of triphenylphosphine and the appropriate carbon tetrahalide with 2,3-dihydro-3-oxobenzo[b]telluro-phene (80BSB763). 

Pyridones can also be converted to 2-chloropyridines by exchanging the carbonyl functionality using phosphoroxychloride (POCI3) [72]. A combination of N-halosuccinimides and triphenylphosphine has also been applied to introduce halogens in this position [73]. The carbonyl functionality in 2-pyridones makes these systems reactive towards nucleophiles as well, which add in 1,4-reactions with displacement of halides [74]. The use of transition metal mediated couplings like Heck, and Suzuki have also been successfully applied on halogenated 2-pyridones (d. Scheme 10) [36,75]. 

Halogenation of 106 with triphenylphosphine, iodine, and imidazole provided the iodo derivative 109. On treatment with lithium aluminum hydride, 109 was converted into two endocyclic alkenes, 110 and di-O-isopro-pylidenecyclohexanetetrol, in the ratio of 2 1. Oxidation of 110 with dimethyl sulfoxide - oxalyl chloride afforded the enone 111.1,4-Addition of ethyl 2-lithio-l,3-dithiane-2-carboxylate provided compound 112. Reduction of 112 with lithium aluminum hydride, and shortening of the side-chain, gave compound 113, which was converted into 114 by deprotection. ... 

B. Nucleophilic Attack on Halogen.- (/ )-( +)-2,2-dimethylpropan( H)ol has been converted to the chloride with inversion of configuration using triphenylphosphine and carbon tetrachloride. The corresponding reaction using carbon tetrabromide gave the bromide with considerable racemiza-tion. ... 

Bromo-j3-nitrostyrene and triphenylphosphine in dry benzene gave the phosphonium bromide (47). Using methanol as the solvent, the rearranged product (48) was formed, possibly via an azirine intermediate. Substituted -bromo-/3-nitrostyrenes yield the phosphoranes (49) and a phosphonium salt. When the aryl group is electron-donating, the reaction follows a different course to form the styrene (50) by initial attack of the phosphine on halogen. 

A variety of reagents can function as the electrophile E+ in the general mechanism. The most useful synthetic procedures for preparation of halides are based on the halogens, positive halogens sources, and diethyl azodicarboxylate. A 1 1 adduct formed from triphenylphosphine and bromine converts alcohols to bromides.15 The alcohol displaces bromide ion from the pentavalent adduct, giving an alkoxyphosphonium intermediate. The phosphonium ion intermediate then undergoes nucleophilic attack by bromide ion, forming triphenylphosphine oxide. 

Several modifications of procedures based on halophosphonium ion have been developed. Triphenylphosphine and imidazole in combination with iodine or bromine gives good conversion of alcohols to iodides or bromides.22 An even more reactive system consists of chlorodiphenylphosphine, imidazole, and the halogen,23 and has the further advantage that the resulting phosphorus by-product diphenylphosphinic acid, can be extracted with base during product workup. 

Carboxylic acids can be converted to acyl chlorides and bromides by a combination of triphenylphosphine and a halogen source. Triphenylphosphine and carbon tetrachloride convert acids to the corresponding acyl chloride.100 Similarly, carboxylic acids react with the triphenyl phosphine-bromine adduct to give acyl bromides.101 Triphenviphosphine-iV-hromosuccinimide also generates acyl bromide in situ.102 All these reactions involve acyloxyphosphonium ions and are mechanistically analogous to the alcohol-to-halide conversions that are discussed in Section 3.1.2. 

Nucleophilic Attack at Halogen.- Further applications of tertiary phosphine-tetrahalogenomethane and related "reagents" have been described. The reactions of primary and secondary alcohols with potassium carboxylates in the presence of the triphenylphosphine-tetrachloromethane reagent lead to the formation of esters in good yield. However, application of this procedure... 

Then, selective halogenation has been carried out at mild conditions under which only the halogenation of the two primary hydroxyl groups occurs. The secondary hydroxyl groups remain intact under these conditions. The reaction proceeds smoothly with carbon tetrachloride and triphenylphosphine in anhydrous pyridine at 5°C for 18 hours (22). 1,6-Dichloro-1,6-dideoxy-3,4-0-isopropyli-... 

Considerable interest has developed in the method of conversion of alcohols, by their reaction with carbon tetrachloride and tertiary phosphines (usually triphenylphosphine), into the corresponding alkyl chlorides.65 The reaction is considered to proceed by an ionic mechanism involving nucleophilic displacement on halogen, as shown. 

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