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An efficient conversion of Alcohols to Alkyl bromides using pyridinium based

ionic liquids: A green alternative to Appel Reaction

Article  in  Asian Journal of Chemistry · February 2018

DOI: 10.14233/ajchem/2018.20186

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 Asian Journal of Chemistry; Vol. 30, No. 3 (2018), 651-654

ASIAN JOURNAL OF CHEMISTRY

https://doi.org/10.14233/ajchem.2018.21086

An Efficient Conversion of Alcohols to Alkyl Bromides Using Pyridinium

Based Ionic Liquids: A Green Alternative to Appel Reaction

PRANAB J. DAS*, JUPITARA DAS and DIMPEE DAS

Department of Chemistry, Gauhati University, Guwahati-781 014, India

*Corresponding author: E-mail: pranabjdas52@gmail.com

Received: 10 October 2017; Accepted: 8 January 2018; Published online: 31 January 2018; AJC-18760

Pyridinium based ionic liquids namely 4-alkylpyridinium bromides were prepared and used for the conversion of alcohols to alkyl
bromides in the presence of p-toluenesulphonic acid in the absence of volatile organic compounds. This solvent free procedure promises
to be a much improved and environmentally benign alternative to the Appel reaction.

Keywords: Appel reaction, Ionic liquid, Solvent free synthesis, Alkylbromides, Aliphatic alcohol.

INTRODUCTION The need for environmentally acceptable processes has

fuelled great interest towards the use of benign reagents espe-
Alkyl halides are widely used as industrial solvents and cially the use of ionic liquids to promote reactions. Generally
also as essential precursors for the preparation of a variety of reactions promoted by ionic liquids results in reduced reaction
fine chemicals. The classical procedure for the conversion of time, simplifies product recovery and greatly improves turn
alcohols to alkyl haides is termed as the Appel reaction and over. Leadbeater et al. [10] used imidazolium based ionic
in the classical example requires the use of NaBr and H2SO4 liquids, which played the dual role as a reagent and as a solvent
under harsh reaction conditions [1]. Being and environmentally in microwave mediated technique for the conversion of
unacceptable process, this synthesis has limited synthetic alcohols to the alkyl halides in the presence of mineral acids.
applicability today. A direct conversion of alcohols to alkyl Ren and Wu [11] used 1,3-dimethylimidazolium halide as
halides is difficult due to poor leaving group characteristics of reagent for the conversion of n-butanol and n-octanol to the
the hydroxyl group, however several improved procedures have corresponding halide in the presence of bronsted acids such as
been reported to overcome this drawback. An elegant proce- HCl, H2SO4 and CH3SOOH. Petten et al. [12] used halodehydro-
dure for the conversion was reported wherein triphenylphos- genation technique using ionic liquid for the conversion of
phine and tetrahaloalkanes were used [2]. Other notable syn- long chain alcohols to their respective alkyl halides, Ranu and
thetic procedures are the Mitsunobo reaction [3], the reaction Jana [13] reported a stereoselective one pot conversion combi-
of 2,4,6-trichloro-[1,3,5]-triazine (TCT) in DMF followed by ning the use of ionic liquid and ultrasound and finally a stereo-
addition of CH2Cl2 solution of the reactant alcohol [4], the selective one pot conversion of N,N’-diisopropylcarbodiimide
reaction of alcohol with 2,3-trichloro-5,6-dicyanobenzo-quinone was reported [14] besides others [15,16].
in the presence of triphenyl phosphine, CH2Cl2 and a phase
transfer catalyst [5]. ROMP-gel supported triphenyl-phosphine EXPERIMENTAL
[6], phosphorus(V) mediated nucleophilic substitution reaction GC/MS was carried out on a Perkin Elmer Clarus 600 gas
[7] and finally the use of fluorous phosphine [8] besides others. chromatograph and Clarus 600C mass spectrometer (column
The previously reported procedures suffer from the use of toxic 30.0 m × 250 µm). 1H was done on a Bruker 300 MHz instru-
and expensive reagents and further the use of triphenylphosphine ment using CDCl3 as the solvent, 4-methylpyridine, ethyl-
makes product recovery difficult and time consuming specially bromide, n-butylbromide, n-octylbromide, substrate alcohols
due to the in situ formation of the phosphane oxide. In order and p-toluenesulphonic acid were purchased from Sigma
to avoid the use of triphenylphosphine, an elegant phosphine Aldrich and were used as received. The ionic liquids, 1-n-alkyl-
free halogenation protocol using a visible light photoredox 4-methylpyridinium bromide, were prepared from 4-methyl-
catalyst Ru(bpy)3Cl2 was reported [9]. pyridine and characterized.
652 Das et al. Asian J. Chem.

Thermogravimetric analysis (TGA): TGA experiments which could be identified by running GC with authentic sample.
were performed using a TGA-DSC1, Mettler Toledo instru- Products were examined for their purity by TLC using silica
ment. The samples were weighed and placed in a platinum gel plates and n-hexane:petroleum ether (40-60) (9:1) as the
crucible. They were then heated in a stream of nitrogen atmos- eluent.
phere, from room temperature to 700 °C with a heating rate Recovery of 1-n-butyl-4-methylpyridinium-p-toluene-
usually of 10 °C/min. sulphonate: After separation of the products, the precipitated
General method for preparation of ionic liquids: Three ionic liquid was found to be transformed to the p-toluene-
different pyridinium based ionic liquids namely 1-ethyl-4- sulphonate. For further purification, 25 mL petroleum ether
methyl pyridinium bromide, 1-n-butyl-4-methyl pyridinium bromide (40-60 °C) was added to this and stirred for 5 min to remove
and 1-n-octyl-4-methyl pyridinium bromide were prepared by any trace of alkyl bromides. The petroleum ether layer on
simply mixing 4-methylpyridine (γ-picoline) and the appro- evaporation afforded the 1-n-butyl-4-methyl-pyridinium-p-
priate alkyl halide and stirring the mixture in the dark for 20- toluenesulphonate, which was recovered and stored in dessi-
24 h (Scheme-I). The yield of the ionic liquids was found to ccator. The recovered product was identified as the sulphonate
be almost quantitative. form by 1H NMR spectra. 1H NMR (300 MHz, CDCl3): δH
ppm 8.915 (d, 2H, J = 6.3 Hz, ArH), 7.740-7.685 (m, 4H,
ArH), 7.112 (d, 2H, J = 7.8 Hz, ArH), 4.612 (t, 2H, J = 7.2 Hz,
2H, NCH2), 2.520 (s, 3H, ArCH3), 2.303 (s, 3H, ArCH3), 1.867-
1.767 (m, 2H, CH2), 1.292-1.192 (m, 2H, CH2), 0.840 (t, 3H,
Stirring
+ R Br J = 7.2 Hz, CH3); 13C NMR (75 MHz, CDCl3): δ ppm 158.38,
24-30 hr 143.51, 139.58, 128.50, 125.50, 60.44, 32.94, 21.61, 20.93,
N N 18.79, 13.10. The sulphonate form of the ionic liquid was
R = C2H5, C4H9, C8H17 Br converted to the bromide form by treatment with 30 % HBr.
R
Scheme-I RESULTS AND DISCUSSION

1-Ethyl-4-methylpyridinium bromide: m.f.: C8H12NBr, In all reported synthetic methods, the imidazolium based
white solid, melting range 250-300 °C; 1H NMR (300 MHz, ionic liquids were use as the promoter. These ionic liquids are
CDCl3, Me4Si) (δH ppm): 9.322 (2H, d, J = 6.6 Hz, pyr-CH), costly, less effective and the methods reported requires high
7.756 (2H, d, J = 6.3Hz, pyr-CH), 4.803 (2H, q, J =7.2Hz, pressure and long reaction time and the procedures are limited
CH2), 2.503 (3H, s, CH3),1.532 (3H, t, J = 7.2 Hz, CH3); 13C to a few selected alcohols and could not be generalized. Search
NMR (75 MHz, CDCl3) (δ ppm): 158.53, 143.85, 128.72, for inexpensive, efficient and environmentally benign methods
56.12, 22.03, 17.03. for carrying out the Appel reaction is still being explored. In
1-n-Butyl-4-methyl pyridinium bromide: m.f.: C10H16NBr, order to overcome the disadvantages associated with the use
nature: white waxy solid, melting range 110-280 °C; 1H NMR of immidazolium based ionic liquids, we examined the possi-
(300 MHz, CDCl3, Me4Si) (δH ppm): 9.363 (2H, d, J = 6.6 Hz, bility of the use of pyridinium based ionic liquids for promoting
pyr-CH), 7.840 (2H, d, J = 6.0 Hz, pyr-CH), 4.812 (2H, t, J = the Appel reaction for the conversion of alcohols to the alkyl
7.2 Hz, CH2), 2.577 (3H, s, CH3), 1.972-1.872 (2H, m, CH2), bromides. The results reported herein indicate the superiority
1.381-1.282 (2H, m, CH2), 0.853 (3H, t, J = 7.2 Hz, CH3); 13C of pyridinium based ionic liquids vis-a-vis imidazolium coun-
NMR (75 MHz, CDCl3) (δ ppm): 158.51, 144.17, 128.70, terparts. The pyridinium based ionic liquids used in this study
60.59, 33.51, 22.08, 19.09, 13.36. were prepared by a simple reported procedure [17] using low-
1-n-Octyl-4-methyl pyridinium bromide: m.f.: C14H24NBr, cost and easily available starting compounds. Three different
nature: light pink waxy solid, melting range 300-400 °C; 1H ionic liquids were prepared starting from 4-methylpyridine
NMR (300 MHz, CDCl3, Me4Si) (δH ppm): 9.338 (2H, d, J = and corresponding alkyl halides namely 1-ethyl-4-methylpyri-
6.3 Hz, pyr-CH), 7.893 (2H, d, J = 6.3 Hz, pyr-CH), 4.872 diniumbromide [1-E-4-MPyr]Br, 1-n-butyl-4-methyl-pyridinium
(2H, t, J = 7.5 Hz, CH2), 2.645 (3H, s, CH3), 2.022- bromide [1-n-B-4Mpyr]Br and 1-n-octyl-methylpyridinium-
1.941 (2H, m, CH2), 1.300-1.204 (10H, m, CH2), 0.824 (3H, bromide [1-n-O-4-Mpyr]Br and characterized. Results indicate
t, J = 6.9 Hz, CH3); 13C NMR (75 MHz, CDCl3) δ: 158.54, that all the ionic liquids have thermal stability upto 250 °C.
144.11, 128.75, 60.93, 31.69, 31.45, 28.82, 25.84, 22.35, Thermogravimetric curves of the three ionic liquids indicate
22.09, 13.87. that 1-n-butyl-4-methyl pyridinium-bromide had a melting
General procedure for the conversion: A mixture of 5 range of 110-280 °C and this being close to the melting range
mmol alcohol, 5 mmol p-toluenesulphonic acid, 5 mmol 1-n- of usual ionic liquids was considered to be the most appropriate
butyl-4-methylpyridiniumbromide was heated in an oil bath of the three ionic liquids for the present synthesis. The TGA
with constant stirring to different temperatures (Table-2), the curves are shown in Fig. 1.
progress of the reactions monitored by GC after 0.5, 1.0, 1.5, The ionic liquids were used as a promoter for a solvent
2.5 and 5 h. In the GC experiments, aliquots of reaction mixture free conversion of a variety of alcohols to the corresponding
drawn, diluted with 1 mL of diethylether, solution filtered and bromides. Initially the efficiency of the individual ionic liquids
GC recorded. After complete conversion as indicated by GC, were screened for their utility. The conversion of octan-1-ol
25 mL of n-hexane was added to precipitate out the ionic liquid. to 1-bromooctane using the three ionic liquids individually
The filtrate on evaporation of the solvent afforded the bromides, was examined as a model reaction and the results summarized
Vol. 30, No. 3 (2018) An Efficient Conversion of Alcohols to Alkyl Bromides Using Pyridinium Based Ionic Liquids 653

(a) (b) (c)

Fig. 1. TGA curve of (a) 1-n-butyl-4-methylpyridiniumbromide (b) 1-ethylpyridiniumbromide (c) 1-n-octylpyridiniumbromide

in Table-1. Results indicates the better efficiency, in terms of of the reaction was monitored by GC of aliquots drawn from
better yield of products, of 1-n-butyl-4-methyl-pyridiniumbromide the reaction mixture at time intervals of 0.5, 1.5, 2.5 and 5 h.
[1-n-B-4Mpyr]Br over other ionic liquids used. Consequently The reaction is shown in Scheme-II and results obtained for a
all subsequent reactions were carried out with using [1-n-B- variety of alcohols summarized in Table-2. The reaction time
4Mpyr]Br. and temperature necessary for complete conversion, varied
with the nature of the substrate alcohol.
TABLE-1
EFFICIENCY OF DIFFERENT PYRIDINIUM BASED Conclusion
IONIC LIQUID FOR CONVERSION OF OCTAN-1-OL TO
n-OCTYLBROMIDE AFTER 5 h OF REACTION TIME The use of pyridinium based ionic liquid for the Appel
reaction offers an easy access to the alkylbromides. The pro-
Reaction % Conversion
Entry Ionic liquid ducts could be isolated by simple filtration of the precipitated
temp. (°C) after 5 h*
1 1-Butyl-4-methylpyridinium 130 100 ionic liquids. The precuts were identified performing GC with
bromide authentic sample. The ionic liquids could be recycled. Simple
2 1-Ethyl-4-methylpyridinium 130 65 reaction condition, absence of costly reagents, high turnover
-bromide
3 1-Octyl-4-methylpyridinium 130 70
of products makes this procedure an improved practical alter-
-bromide native to the conventional Appel reaction.
*% conversion obtained from GC experiments.
ACKNOWLEDGEMENTS
In a typical procedure, an equimolar mixture of alcohol, One of the author, JD is grateful to CSIR, New Delhi for
p-toluenesulphonic acid and 1-n-butyl-4-methylpyridinium- grant of Junior Research Fellowship and another author, DD
bromide was taken in an round bottom flask and heated to the is grateful to University Grand Commission, New Dehi for
optimized temperature for range of reaction time. The progress providing the fellowship under BSR programme.

TABLE-2
SYNTHESIS OF ALKYL BROMIDES FROM ALCOHOLS USING AS THE
IONIC LIQUID [1-B-4-M-Pyr]Br AS THE BROMINATING AGENT
Entry Reactants Products Reaction temp. (°C) Time (h) Conversion (%)
1 Butan-1-ol n-Bromobutane 100 5.0 100
2 Pentan-1-ol n-Bromopentane 130 5.0 100
3 Pent-2-ol 2-Bromopentane 120 7.0 100
4 Hexan-1-ol n-Bromohexane 130 4.0 100
5 Cyclohexanol Bromocyclohexane 140 5.0 100
6 Heptan-1-ol n-Bromoheptane 130 5.0 100
7 Octan-1-ol n-Bromooctane 140 2.5 100
8 Benzyl alcohol Benzyl Bromide 140 0.5 100
9 4-chlorobenzyl alcohol 4-Chlorobenzyl Bromide 140 1.0 100

N
PTSA
R OH + N R Br + SO3 + H O
2
alcohols Br alkyl bromides

Where R= CH3 (CH2) n- where n= 3,4,5,6,7

= C6 H11 , C6 H5CH2 , 4-ClC6 H4 CH2-
Scheme-II: Conversion of alcohols to alkylbromides using pyridinium based ionic liquids
654 Das et al. Asian J. Chem.

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