Bromine, reaction with phenylacetylene

Bromine, reaction with phenylacetylene and sodium hydroxide to give phenylbromoethyne, 46, 86 N-Bromoacetamide, as reagent for bromofluorination of 1-heptene, 46,10... 

Compounds containing active hydrogen atoms (pK = 11-25) could be brominated when DBU was added dropwise into a mixture of substrate (phenylacetylene, diethyl butylmalonate, indene, or fluorene) and BrCClj in benzene (78CL73). Compounds with lower acidity (pK 29) exhibited no reaction. With more acidic derivatives (diethyl malonate and benzyl cyanide), oxidative dimerization also occurred. Oxidative dimerization also took place when BrCClj was added dropwise into a solution of active methylene compound and DBU in benzene. The ratio of the reaction products depended on the ratio of DBU and BrCCIj. 

The first report of a Sonogashira coupling reaction of an oxazole was by Yamanaka in 1987. Oxazoles substituted with bromine at the 4- or 5-positions were coupled with phenylacetylene yielded the alkyne in 83% and 89% yield, respectively. The Sonogashira reaction with 2-halooxazoles was not attempted however, 2-halothiazoles and 2-halo-A -methylimidazoles were subjected to Sonogashira conditions. Yields in both cases were low and not synthetically useful. 

PROBLEM 10.66 Many additions of bromine to acetylenes give only trans dibromide intermediates. However, there are exceptions. Here is one. Elxplain why phenylacetylene gives both cis and trans dibromides on reaction with bromine. 

Electrophilic. Electrophilic addition of bromine to acetylenes has received much less attention than the corresponding reaction with olefins. At low bromine concentration and in the absence of bromide ion, the rate of bromina-tion of ring-substituted phenylacetylenes correlates well with values. The P value of —5.17 is interpreted in terms of a transition state leading to a vinyl cation intermediate (70) and, in agreement, addition is non-stereospecific. 

Bromination usually follows a two-step mechanism, the rate-limiting step involving formation of an adduct with Br. Calculate energies for Br addition to phenylacetylene and styrene, leading to phenylacetylene+Br+ and styrene+Br+, respectively. (The energy of Br+ is given at right.) Which reaction is more favorable Is this the same preference as seen for Br2 addition ... 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

Phenylacetylene on heating with NIS in methanol and catalytic amounts of HTI was transformed to the diiodo acetal PhC(OMe)2CHI2 (95%) under similar conditions, iodo-phenylacetylene afforded PhC(OMe)2COOMe (86%) [56]. Other reactions using NBS or NIS and catalytic HTI resulted in bromination and iodination of, respectively, polyalkylbenzenes [57] and A-acyl-2,3-dihydro-4-pyridones [58]. 

Styrene dibromide [(l,2-dibromoethyl)benzene], pure enough for later conversion into phenylacetylene, is obtained by slowly dropping a solution of bromine (80 g) in CC14 (100ml) into one of styrene (52 g) in CC14 (50 ml) with vigorous stirring at —10 to —15° towards the end of the reaction the mixture is cooled in water or ice to prevent its premature solidification. After a short time the product is filtered off and dried in the air (yield 90-95 %) 44... 

Bongini and coworkers converted an Amberlyst bromide into the perbromide by treatment with a carbon tetrachloride solution of bromine. On storage, only a small decrease in active bromine content was observed. This reagent converted phenylacetylene dissolved in dichloromethane, to an approximately 1 3 cisItransmiyXmQ of the 1,2-dibromo addition product in 92% yield at room temperature in 1 h. A similar result was obtained with 1-hexyne, although the reaction required refluxing for 3h. When the Amberlyst bromide had been treated with a dichloromethane solution of chlorine, the polymer acted as a chlorobromination agent. 

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