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Facile reductive dehalogenation of organic halides with nickel boride at ambient temperature Jitender M. Khurana, Sanjay Kumar, and Bhaskara Nand
Abstract: The hydrodehalogenation of a series of aryl, alkyl, allyl, and benzyl chlorides, bromides, and iodides has been carried out efficiently using nickel boride in methanol at ambient temperature, leading to the corresponding products resulting from hydrogen/halogen exchange. Key words: hydrodehalogenation, reduction, organic halides, sodium borohydride, nickel boride. Résumé : Faisant appel à l’action du borure de nickel à la température ambiante et dans le méthanol, on a effectué d’une façon efficace la hydrodéshalogénation d’une série d’iodures, de bromures et de chlorures d’aryle, d’alkyle, d’allyle et de benzyle conduisant à la formation des produits correspondants résultant d’un échange hydrogène/halogène. Mots-clés : hydrodéshalogénation, réduction, halogénures organiques, borohydrure de sodium, borure de nickel. [Traduit par la Rédaction]
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Introduction The development of effective procedures for the dehalogenation of organic halides is an important task, as it helps in the reduction of pollution by halogen-containing industrial wastes as well as for the synthesis of fine chemicals. Unlike oxidation methods, reductive dehalogenation processes are advantageous, as no toxic side products are formed. A wide variety of hydrodehalogenating systems have been used over the years and have been reviewed in detail (1–3). Thus, catalytic hydrogenation (4), dehalogenation by metals or low-valent metal compounds (5), metal hydrides, or complex metal hydrides (6–10) are some general reagents and methods able to accomplish the abovementioned transformation. Nickel boride (11), first reported by Schlesinger and Brown, has been used as heterogeneous hydrogenation catalyst over the years (12). However, it is now known as a reducing agent by itself because of the adsorbed hydrogen (13). In recent years, we have used nickel boride as a novel reducing agent in multifarious transformations (14a–14m) (e.g., reductions, deoxygenations, desulfurisations, and so forth). In continuation to our studies on dehalogenation of various types of organic halides (15), we now wish to report the dehalogenation of benzylic, allylic, aryl, and alkyl halides with nickel boride in methanol at ambient temperature.
Results and discussion In this paper, we report hydrodehalogenation of aryl, alkyl, and allyl halides to the corresponding hydrocarbons
using nickel boride generated in situ from nickel(II) chloride and sodium borohydride. Benzylic halides were almost instantaneously reduced. Allylic halides underwent hydrodehalogenation and reduction of double bond concomitantly. Aryl halides, which are generally resistant to hydrodehalogenation, could also be easily dehalogenated to the corresponding arenes. 9-Bromofluorene was chosen as the model substrate to investigate and optimize the conditions for hydrodebromination of benzylic halides. The reactions of 9-bromofluorene were carried out with nickel boride in different solvents and in different molar ratios of substrate to nickel boride to achieve the desired transformation. Reactions carried out in THF, ethanol, and DMF were sluggish and gave a mixture of products, while no reaction was observed in acetonitrile and dichloromethane. Reaction of 9-bromofluorene in methanol yielded 96% fluorene in 15 min at ambient temperature. Further, it has been shown that the hydrodehalogenation is proceeding due to in situ formation of nickel boride, as no reaction of 9-bromofluorene was observed with nickel(II) chloride or sodium borohydride independently. The hydrodehalogenation of a variety of benzylic halides was subsequently investigated under similar experimental conditions. Benzylic chlorides, bromides, and iodides underwent rapid hydrodehalogenation in different molar ratios of substrate:NiCl2·6H2O:NaBH4 (Scheme 1) (Table 1). The ease of dehalogenation BnI > BnBr > BnCl follows the order of bond energies C–Cl > C–Br > C–I, which is evident from molar ratios and the time required for the dehalogenation (Table 1, entries 1–21). Further, it can also be inferred from Table 1 that primary halides (Table 1, entries 1–4, 11, 12,
Received 6 August 2008. Accepted 15 September 2008. Published on the NRC Research Press Web site at canjchem.nrc.ca on 24 October 2008. J.M. Khurana,1 S. Kumar, and B. Nand. Department of Chemistry, University of Delhi, Delhi 110007, India. 1
Corresponding author (e-mail:
[email protected]).
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doi:10.1139/V08-156
© 2008 NRC Canada
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Table 1. Reductive dehalogenation of organic halides with nickel boride in methanol at room temperature. Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
Substrate (S)
Molar ratio S/NiCl2·6H2O/NaBH4
Time (min)
Product
Yield (16) (%)
1-(Bromomethyl)naphthalene 2-(Bromomethyl)naphthalene 4-Bromobenzyl bromide 4-chlorobenzyl bromide 9-Bromofluorene Bromodiphenylmethane (1-Bromoethyl)benzene (1-Bromopropyl)benzene 1-(1-Bromoethyl)naphthalene Bromotriphenylmethane 1-(Chloromethyl)naphthalene 2-(Chloromethyl)naphthalene 9-Chlorofluorene Chlorodiphenylmethane (1-Chloroethyl)benzene (1-Chloropropyl)benzene 1-(1-Chloroethyl)naphthalene Chlorotriphenylmethane 1-(Iodomethyl)naphthalene (1-Iodopropyl)benzene Iododiphenylmethane Cinnamyl iodide Cinnamyl bromide Cinnamyl chloride 1-Iodonaphthalene 1-Bromonaphthalene 1-Chloronaphthalene 9-Bromoanthracene 9-Chloroanthracene 9-Bromophenanthrene 4-Bromobiphenyl 4-Bromophenol 4-Chlorophenol Methyl 4-bromobenzoate Methyl 4-chlorobenzoate 1-Bromododecane 1-Bromohexadecane 1-Bromoadamantane 1-Bromo-3-phenylpropane Methyl 4-bromobutanoate
1:2:6 1:2:6 1:2:6 1:2:6 1:2:6 1:2:6 1:2:6 1:2:6 1:2:6 1:2:6 1:3:9 1:3:9 1:3:9 1:3:9 1:3:9 1:3:9 1:3:9 1:3:9 1:1:3 1:1:3 1:1:3 1:1:3 1:1:3 1:2:6 1:1:3 1:2:6 1:3:9 1:2:6 1:3:9 1:2:6 1:10:30 1:10:30 1:10:30 1:10:30 1:10:30 1:5:15 1:5:15 1:5:15 1:5:15 1:5:15
15 15 15 15 15 20 20 30 20 40 20 20 25 30 30 30 25 45 5 10 10 10 15 10 15 15 25 30 30 30 120 60 90 45 60 20 20 35 30 30
1-Methylnaphthalene 2-Methylnaphthalene 4-Bromotoluene 4-Chlorotoluene Fluorene Diphenylmethane Ethylbenzene n-Propylbenzene 1-Ethylnaphthalene Triphenylmethane 1-Methylnaphthalene 2-Methylnaphthalene Fluorene Diphenylmethane Ethylbenzene n-Propylbenzene 1-Ethylnaphthalene Triphenylmethane 1-Methylnaphthalene n-Propylbenzene Diphenylmethane n-Propylbenzene n-Propylbenzene n-Propylbenzene Naphthalene Naphthalene Naphthalene Anthracene + 9,10-Dihydroanthracene Anthracene + 9,10-Dihydroanthracene Phenanthrene Biphenyl Phenol Phenol Methyl benzoate Methyl benzoate n-Dodecane n-Hexadecane Adamantane n-Propylbenzene Methyl butanoate
92 86 85 81 96 90 83 81 82 81 94 92 91 75 81 84 74 86 85 85 82 81 91 92 87 95 93 42 + 48 40 + 47 86 54 72 75 84 82 85 84 82 87 78
Scheme 1.
and 19) undergo faster reduction than secondary halides (Table 1, entries 5–9, 13–17, 20, and 21), and tertiary halides (Table 1, entries 10 and 18) exhibit even slower reactivity. Hydrodehalogenation of allylic halides (Table 1, entries 22–24), on the other hand, proceeds with the concomitant reduction of double bond to give the completely reduced product. No selective dehalogenation could be achieved even at lower temperatures.
Aryl halides and alkyl halides, which are generally resistant to dehalogenation, could also be dehalogenated successfully with nickel boride (Scheme 1). Thus, 1-iodonaphthalene, 1-bromonaphthalene, and 1-chloronaphthalene underwent rapid dehalogenation (Table 1, entries 25–27) giving naphthalene in excellent yields. The order of reactivity was the same as observed earlier, i.e., I > Br > Cl. Reaction of 9-bromoanthracene and 9-chloroanthracene with nickel boride (Table 1, entries 28 and 29) resulted in a mixture of anthracene and 9,10-dihydroanthracene. This is because anthracene itself was observed to undergo reduction with nickel boride to give 9,10-dihydroanthracene in an independent reaction. Similarly, other aryl halides 9-bromophenanthrene, 4bromophenol, 4-chlorophenol, methyl 4-bromobenzoate, © 2008 NRC Canada
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methyl 4-chlorobenzoate, and 4-bromobiphenyl were easily dehalogenated in quantitative yields. Dehalogenation of halobenzenes, however, required much higher molar ratios compared with halonaphthalenes and benzylic halides. This fact has been utilized to achieve regioselective dehalogenation of benzylic C–X over Ph–X bond. Thus, 4bromobenzyl bromide and 4-chlorobenzyl bromide could be selectively dehalogenated to give 4-bromotoluene and 4chlorotoluene, respectively (Table 1, entries 3 and 4). Aliphatic alkyl halides, 1-bromohexadecane, 1-bromododecane, 1-bromoadamantane, 1-bromo-3-phenylpropane, and methyl 4-bromobutanoate also underwent successful dehalogenation but required higher molar ratio of 1:5:15 (Table 1, entries 36–40). Selective debromination of benzylic bromide over alkyl bromide could also be achieved when an equimolar mixture of 1-(bromomethyl)naphthalene and 1-bromo-3-phenyl propane was treated with nickel boride in 1:2:6 molar ratio. 1H NMR spectra after 15 min showed complete disappearance of 1-(bromomethyl)naphthalene while 1-bromo-3-phenyl propane was found unreacted in the reaction mixture. In conclusion, we have developed a highly efficient protocol for hydrodehalogenation of organic halides with nickel boride at ambient temperature. Compared with other hydrodehalogenating systems, several features make the procedure particularly attractive. Hydrogenolysis was very rapid. Yields of products were found good to excellent. Further, no coupled product or any other side product was either detected or isolated. Reaction was carried out at ambient temperature, and the products could be isolated by a simple workup procedure. However, the carbonyl and nitro groups are sensitive to nickel boride and get reduced (14c, 17).
Experimental All products are known compounds. Melting points were recorded on a Tropical Labequip apparatus and are uncorrected. The PMR spectra were recorded on Hitachi FTNMR (60 MHz) using TMS as internal standard. The products were identified by mp and superimposable IR and NMR spectra with authentic samples. Methanol (S.D. Fine), nickel chloride hexahydrate (S.D. Fine), and sodium borohydride (E. Merck) were used in all reactions. General procedure In a typical reaction, a 50 mL round-bottomed flask fitted with a reflux condenser was mounted over a magnetic stirrer, and 9-bromofluorene (0.2 g, 0.81 mmol) dissolved in 10 mL of methanol was placed in it. NiCl2·6H2O (0.38 g, 1.63 mmol) was added followed by NaBH4 (0.18 g, 4.89 mmol) cautiously. The reaction mixture was stirred vigorously at room temperature. The progress of reaction was monitored by TLC using petroleum ether as eluent. TLC of the reaction mixture showed the complete disappearance of starting material after 15 min. The reaction was quenched by adding 10 mL of methanol. The reaction mixture was filtered through a Celite pad (~2.5 cm) and washed with methanol (20 mL). Water (20 mL) was added to the filtrate, which was extracted with ethyl acetate (3 × 10 mL). The
Can. J. Chem. Vol. 86, 2008
combined extract was dried over anhyd. MgSO4, decanted through a cotton pad, and concentrated on a rotary evaporator. The product was recrystallized from ethanol to give 0.13 g of fluorene as characterized by mp and 1H NMR spectra.
Acknowledgement Financial assistance for the project by University Grants Commission [Project no. F-32–203/2006 (SR)] and Junior/ Senior Research Fellowship to SK by Council of Scientific and Industrial Research is gratefully acknowledged.
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