Hydrobromination of alkenes with PBr3/SiO2: a simple and efficient regiospecific preparation of alkyl bromides

Abstracts

The reaction of several alkenes with 0.4 mol equiv. PBr3/SiO2 in dichloromethane at room temperature gave the alkyl bromides with Markovnikov regiospecificity in 50 - 100% yield and short reaction time. Isoprene at - 8 °C in these conditions gave 1-bromo-3-methyl-2-butene only (54%).

alkenes; bromides; electrophilic addition; regiospecificity; silica

A reação de diversos alquenos com 0,4 equiv. mol de PBr3/SiO2 em diclorometano à temperatura ambiente forneceu os brometos de alquila com regiospecificidade Markovnikov em 50 - 100% de rendimento e tempos curtos de reação. O isopreno a - 8 °C nestas mesmas condições forneceu somente o 1-bromo-3-metil-2-buteno em 54%

Short Report

Hydrobromination of Alkenes with PBr₃/SiO₂: a Simple and Efficient Regiospecific Preparation of Alkyl Bromides

Antonio M. Sanseverino and Marcio C.S. de Mattos ^*

Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, CP 68545, 21945-970, Rio de Janeiro - RJ, Brazil

A reação de diversos alquenos com 0,4 equiv. mol de PBr₃/SiO₂ em diclorometano à temperatura ambiente forneceu os brometos de alquila com regiospecificidade Markovnikov em 50 - 100% de rendimento e tempos curtos de reação. O isopreno a - 8 ^oC nestas mesmas condições forneceu somente o 1-bromo-3-metil-2-buteno em 54%

The reaction of several alkenes with 0.4 mol equiv. PBr₃/SiO₂ in dichloromethane at room temperature gave the alkyl bromides with Markovnikov regiospecificity in 50 - 100% yield and short reaction time. Isoprene at - 8 ^oC in these conditions gave 1-bromo-3-methyl-2-butene only (54%).

Keywords: alkenes, bromides, electrophilic addition, regiospecificity, silica

Introduction

Surface mediated reactions are of great utility in organic synthesis, and in many cases the products are obtained in better yields and improved selectivities than in a homogeneous media in solution^1-3. The reagents or catalysts can be supported^1-3 or unsupported in these reactions⁴.

Organic halides are important compounds in organic synthesis, where functional group interconversions mediated by substitution reactions (radical or ionic) are of great utility⁵. HBr adds readily to most alkenes predominantly with Markovnikov regioselectivity^6,7. However, unless the substrate is rigorously purified (alkenes readily absorb oxygen from the air) and the reaction media is isolated from light and air to avoid formation of small amounts of peroxides, competing radical-chain addition to give the anti-Markovnikov products occurs⁸. As the generation and transfer of the hygroscopic gas HBr is inconvenient and difficult to perform stoichiometrically^6,7, alternate methodologies for performing hydrobromination of alkenes are of great interest.

Kropp and co-workers showed that oxalyl bromide or bromotrimethylsilane undergo hydrolysis on the surface of silica gel to generate HBr in situ⁷, which produces alkyl or alkenyl bromides in high yields via highly Markovnikov additions to carbon-carbon double or triple bonds⁶. This methodology has the advantage of not requiring anhydrous conditions nor generation of toxic and corrosive gaseous HBr.

Surprisingly, although Kropp studied the reaction of (COBr)₂ and Me₃SiBr/SiO₂ with 1-octene only⁷, no study was done with PBr₃. This latter reagent is easily available and cheaper than the previous ones⁹ and also more efficient in terms of the stoichiometry of the reaction, as only one mol equiv. of PBr₃ would generate 3 mol equiv. of HBr in its reaction with water (Scheme 1). Furthermore, PBr₃ is more useful in terms of atom economy¹⁰ than (COBr)₂ and Me₃SiBr.

In previous communications we showed that the hydrohalogenation of (R)-limonene with SOCl₂/SiO₂¹¹ and PBr₃/SiO₂¹² produces chemo- and regiospecifically the respective a-terpinyl halides. Now we studied the scope of the hydrobromination of alkenes with PBr₃/SiO₂ and communicate our results.

Results and Discussion

The reaction of styrene (10 mmol) with PBr₃ (0.4 mol equiv.) was studied in the presence of SiO₂ (5 g) in CH₂Cl₂ in an open flask at room temperature (rt). The reaction led to a quantitative yield of 1-bromo-1-phenylethane, with purity greater than 99% (by HRGC- High Resolution Gas Chromatography) in only 20 min. A control experiment was also made in the absence of SiO₂ where 1 mol equiv. of water was added to the reaction media. The results indicate that the presence of SiO₂ is really important, as in its absence the reaction was not complete in the same reaction time (88%, crude yield).

Based on the above results we made a systematic study of the reaction of diverse alkenes and 0.4 mol equiv. of PBr₃/SiO₂ and the results are shown in Scheme 2 and Table. In all cases only the Markovnikov addition products were obtained and no trace of the regioisomeric anti-Markovnikov bromides were detected using all analytical techniques (HRGC, ¹H and ¹³C NMR). The alkyl bromides were obtained in 50 - 79% isolated yield (> 95 - 99% purity by HRGC) and were characterised by physical¹³ and spectroscopic data.

Interestingly, under similar conditions, isoprene at - 8 ^oC underwent exclusively 1,4-addition to afford the corresponding monobromide in 54% isolated yield and greater than 99% purity by HRGC. The reaction time was considerably shorter than the reported literature method, which takes 5 h or more to give the product¹⁴. Oncemore, there is no need of anhydrous conditions nor generating dry gaseous HBr as reported¹⁴.

In summary, the reaction of alkenes with PBr₃/SiO₂ in CH₂Cl₂ is an easy and efficient way to prepare alkyl bromides with Markovnikov regiospecificity. Furthermore, our methodology avoids the need of drying chemicals, rigorous exclusion of moisture, light, and oxygen from the reaction media, and manipulation/generation of dry toxic and corrosive gaseous HBr.

Experimental

Isoprene was distilled prior to use, and the other alkenes were used as received. SiO₂ (Aldrich, 270-70 MESH, 60 Å) was used as received¹⁵, PBr₃ (Merck), and other chemicals were also used as received. ¹Hand ¹³C NMR were acquired on a Bruker AC-200 (200 MHz and 50 MHz, respectively) spectrometer in CDCl₃ solutions with TMS as internal standard. IR spectra were recorded on a Perkin-Elmer 1600 FT-IR spectrometer (KBr film). Analyses by HRGC were performed on a HP-5890-II gas chromatograph with FID by using a 28 m (length), 0.25 mm (ID) and 0.50 mm (phase thickness) RTX-5 silica capillary column and H₂ (flow rate 50 cm s^-1) as carrier gas (split 1:10). Oven temp.: 70 ^oC then 8 ^oC/min to 300 ^oC, injector temp.: 260 ^oC, detector temp.: 280 ^oC.

General procedure for the preparation of alkyl bromides

To a stirred suspension of the appropriated alkene (10 mmol) and SiO₂ (5 g) in CH₂Cl₂ (25 cm³), a solution of PBr₃ (4 mmol) in CH₂Cl₂ (10 cm³) was added for 10 min at rt. After completed addition, the suspension was stirred for several minutes (see Table) and then filtered. The SiO₂ was washed with CH₂Cl₂ (15 cm³), the combined liquid was washed with 10% NaHCO₃ (until no more gas was liberated), brine (2 x) and the organic extract was dried (Na₂SO₄). The solvent was evaporated in a rotatory evaporator at reduced pressure to give the pure alkyl bromide.

1-Bromo-3-methyl-2-butene

A 50 ml flask with CH₂Cl₂ (25 cm³) was charged with isoprene (10 mmol). SiO₂ (5 g) was added slowly followed by a solution of PBr₃ (3.3 mmol) in CH₂Cl₂ (10 cm³), added for 10 min with stirring at - 8 ^oC (bath temperature). The suspension was stirred for aditional 5 min and for 10 min at rt and then worked as above to produce pure 1-bromo-3-methyl-2-butene.

Acknowledgements

AMS thanks CNPq for a fellowship. We thank W. Bruce Kover and Joel Jones Jr. for helpful discussions.

9. (COBr)₂ and Me₃SiBr are considerably more expensive than PBr₃, ca. 3.7 and 3.4 times, respectively. Moreover PBr₃ is also sold as a 1 M solution in CH₂Cl₂ (Aldrich Catalog of Fine Chemicals, 1997).

15. The water content (ca. 15% w/w) was determined by heating in a domestic microwave oven until constant weight.

Received: October 14, 2000

Published on the web: July 7, 2001

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Publication Dates

• Publication in this collection
  01 Nov 2001
• Date of issue
  Oct 2001

History

• Accepted
  07 July 2001
• Received
  14 Oct 2000