Fifth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-5), http://www.mdpi.org/ecsoc-5.htm, 1-30 September 2001

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[E0020]
 

Microwave assisted synthesis of room temperature ionic liquid precursor quaternary salts

in closed vessel

Bhushan M. Khadilkar* and Geeta L. Rebeiro

Applied Organic Chemistry Laboratory, University Dept of Chemical Technology, University of Mumbai, Matunga, Mumbai 400 019, India. E-mail: bhushank@vsnl.com

Received: 15 August 2001 / Uploaded 22 August 2001

ABSTRACT

INTRODUCTION

SCHEME

RESULTS AND DISCUSSION

• TABLE 
• THERMAL PROFILE OF REACTION

EXPERIMENTAL

CONCLUSIONS

ACKNOWLEDGMENT

REFERENCES

ABSTRACT

Various alkylpyridinium and 1-alkyl-3-methylimidazolium halides were synthesized on a large-scale under microwave irradiation, in a closed vessel. The reaction time was drastically reduced as compared to conventional methods, and good yields were obtained.

Key words: Ionic liquid, quaternization, microwave, pyridine, 1-methylimidazole.

INTRODUCTION

Room temperature ionic liquid (RTIL) is no more a new word to a scientific community today. Rising number of publications are indicative of the potential of RTILs as ‘neoteric solvents’ for various chemical reactions. These include Friedel-Crafts reactions^1-3, enzyme catalyzed reactions^4,5, hydrogenations^6,7, benzoylation⁸, Heck reaction⁹, Fischer indole synthesis¹⁰, etc. RTILs are being looked upon as future commercial¹¹ solvents. The acidic ionic liquids can act both as catalyst as well as solvent. This dual property of RTIL has turned out to be a boon in itself to carry out a variety of chemical transformations and is aptly given the name ‘designer solvent’. RTILs¹² known today, are mainly composed of alkylpyridinium or dialkylimidazolium salt and a Lewis acid.

The preparation of some of these salts, e.g. 1-butylpyridinium and 1-butyl-3-methylimidazolium chlorides, required for the widely used RTILs, is quite time consuming. Conventionally it requires as long as 72 hours of reflux^{13, 14}. Our aim was to reduce overall time of preparation of the ionic liquids and to synthesize the precursor salts on a large-scale in shorter time period. While we have been working on microwave assisted synthesis of these salts, recently we came across a report¹⁵ on the preparation of alkyl-3-methylimidazolium salts under microwave irradiation. However, there are some major drawbacks of this method. It is carried out in an open test tube. Hygroscopic nature of salts may not permit a large-scale preparation by this method. Also the irritant volatile alkyl halides as well as the corrosive and hygroscopic 1-methylimidazole, are released inside the microwave cavity and also wasted. Heating volatile materials in an open vessel in microwave oven can be hazardous.

We report here the simple and quick method of preparation of alkylpyridinium and 1-alkyl-3-methylimidazolium salts on a large-scale in a closed vessel under microwave irradiation in CEM make microwave digester, MARS 5.

SCHEME

X= Cl, Br

RESULTS AND DISCUSSION

The quaternization of some alkyl halides like BuBr and PrBr with 1-methylimidazole took place under reflux condition in domestic microwave oven. But alkyl halides like BuCl gave only trace amount of product formation whereas 2-phenylethylchloride, bromohexane, and 2,6-lutidine did not react under reflux condition under microwave irradiation at normal pressure. When we carried out the reaction in closed vessel in a microwave digester, excellent yield of the product was obtained. The microwave digester used for the reaction has a provision for recording temperature and pressure during irradiation. In order to investigate the effect of change in temperature on the reaction, we carried out the reaction of 1-butyl chloride with pyridine and 1-methylimidazole respectively at three different temperatures viz. 100 ^oC, 150 ^oC and 200 ^oC. It was observed that in both the cases at 100 ^oC, under pressure no product was formed, at 150 ^oC maximum conversion of 1-butyl-3-methylimidazolium chloride salt was obtained whereas 1-butylpyridinium chloride was formed only in trace amount. It was only at 200 ^oC that the 1-butylpyridinium chloride salt was formed in quantitative yield. The reaction times were reduced drastically from 72 hours to 1 hour and from 22 hours to 24 min in case of 1-butylpyridinium and 1-butyl-3-methylimidazolium chlorides respectively. This also shows that 1-methylimidazole reacts faster compared to pyridine. The thermal profileof thereaction during microwave irradiation is shown in fig.1and 2. The results are presented in the table below.

TABLE

The optimized results of quaternary salts prepared in closed vessel.

 

Entry	Amine	R-X	bIrradiation Time/ min		Temp oC	Pressurec psi	Yield %
			x	y
1	1-methylimidazole	1-chlorobutane	2	22	150	57	91
2	1-methylimidazole	1-bromobutanea	2.5	-	105	-	99
3	1-methylimidazole	1-bromopropanea	1.6	-	85	-	90
4	Pyridine	1-chlorobutaned	5 +1	30 24	180 200	181 271	66
5	Pyridine	1-bromopropane	1	2	120	29	86
6	Pyridine	1-chloropropane	5	85	150	79	56
7	Pyridine	1-bromobutaned	2 +2	13 3	120 150	10 32	97
8	Pyridine	2-phenethylchloride	5	55	200	56	98
9	Pyridine	1-bromohexane	2	28	120	5	90
10	2,6-lutidine	1-bromobutane	5	55	200	180	58
11	2,6-lutidine	1-chlorobutaned	5 +5	55 25	200 230	180 191	10
12	2,6-lutidine	1-bromopropane	5	55	200	329	83

^aReactions were carried out under reflux in modified domestic microwave oven (Kenstar Model) at 750 W, 30 % power, irradiated for the time given in table & the MW end temp. noted down.

^bx represents the time set to reach the given temp. and y, the hold time to continue irradiation at the given temp.

^c represents maximum pressure reached in the reaction.

^dIn case of BuBr & BuCl, irradiation was done by programming in 2 steps.

THERMAL PROFILE OF REACTION

Fig. 1: Thermal profile of the microwave irradiation of 1-methylimidazole and 1-BuCl.

Fig. 2: Thermal profile of the microwave irradiation of Pyridine and 1-BuCl.

EXPERIMENTAL

Pyridine (S.d. fine grade) and 1-methylimidazole (Merck grade) were dried, distilled and stored over KOH and ethyl acetate was dried over CaH₂. The alkyl halides (commercial grade) were used without further purification.

1. Preparation of 1-butyl-3-methylimidazolium chloride (BMIMC):

¹H NMR (500 MHz, DMSO-d₆):d = 0.86 (t, 3H, J = 7.37 Hz, CH₃), 1.23 (m, 2 H, CH₂), 1.77 (m, 2 H, CH₂), 3.9 (s, 3 H, NCH₃), 4.22 (t, 2 H, J = 7.1 Hz, NCH₂), 7.88 (d, 1 H_arom), 7.96 (d, 1 H_arom), 9.71 (s, 1 H_arom)

¹³C NMR (125 MHz, DMSO-d₆):d = 13.55, 19.04, 31.78, 35.98, 48.6, 122.64, 123.83, 137.15.

2. Preparation of 1-butylpyridinum chloride (BPC):

Pyridine (300 mmol, 24 g) and 1-BuCl (300 mmol, 28 g) were irradiated at 300 W in the microwave digester in two stages: in the 1^st stage it was programmed to 180 ^oC for 5 min, irradiation continued at this temperature for 30 min and in the 2^nd stage the temperature was set to 200 ^oC for 1 min and it was continued at this temperature for another 24 min. Yield: 66 %.

¹H NMR (300 MHz, DMSO-d₆):d = 0.9 (t, 3 H, J= 7.2 Hz, CH₃), 1.3 (m, 2 H, CH₂), 1.94 (m, 2 H, CH₂), 4.69 (t, 2 H, J = 7.2 Hz), 8.1- 9.23 (m, 5 H_arom)

¹³C NMR (300 MHz, DMSO-d₆):d = 13.22, 18.6, 32.68, 60.1, 127.94, 144.86, 145.39.

CONCLUSION

We have developed a very efficient, quick, and practical method for the preparation of alkylpyridinium and 1-alkyl-3-methylimidazolium salts. The pressure reactor used for the reaction is very easy to handle and to set up. The time required to synthesize the salts is reduced by the factor of 72 and 60 in case of BPC and BMIMC respectively, when compared to conventional method.

The use of a closed vessel allows for stoichiometric amounts of alkyl halides to be reacted, instead of excess, with no apparent loss of yield, highlights the ‘green’ aspect of this improved procedure. It also provides a greener and safer synthesis of the ionic liquid precursors, the quaternary salts. In the reported method, reaction is carried out in an open test tube. This poses serious problems of hazards and also results in wastage of the reactants. Our method overcomes all these problems and is far safer.

ACKNOWLEDGMENT

The authors are thankful to B.R.N.S, Dept of Atomic Energy, Govt. of India; A.I.C.T.E., New Delhi, India,  for financial assistance, and G. D. Gokhale Trust, Mumbai, India for awarding fellowship to one of the authors.

REFERENCES

1. Boon JA, Levisky JA, Pflug JL and Wilkes JS, Friedel- Crafts reactions in ambient- temperature Molten salts. J. Org. Chem. 51: 480-483 (1986).
2. Earle M J, Adams C H, Roberts G and Seddon KR, Friedel-Crafts reactions in room temperature ionic liquids. J. Chem. Soc. Chem. Commun. 19: 2097-2098 (1998).
3. Song CE, Shim WH, Roh EJ and Chol JH, Scandium (III) triflate immobilized in ionic liquids: a novel and recyclable catalytic system for Friedel- Crafts alkylation of aromatic compounds with alkenes. J. Chem. Soc. Chem. Commun. 17: 1695-1696 (2000).
4. Schofer S H, Kaftzik N, Wasserscheid P and Kragl U, Enzyme catalysis in ionic liquids: lipase catalyzed kinetic resolution of 1-phenylethanol with improved enantioselectivity. J. Chem. Soc. Chem. Commun. 5 :425-426 (2001).
5. Freemantle M, New Horizons for ionic liquids. Chemistry and Industry Jan 1, 21-25 (2001).
6. Saurez PA, Dullius JE, Einloft S, De Souza RF and Dupont J, The use of new ionic liquids in two phase catalytic hydrogenation reaction by Rhodium complexes. Polyhedron 15: 1217-1219 (1996).
7. Dyson PJ, Ellis DJ, Parker DG and Welton T, Arene hydrogenation in a room temperature ionic liquid using a ruthenium cluster catalyst. J. Chem. Soc. Chem. Commun. 1: 25-26 (1999)
8. Khadilkar BM and. Rebeiro GL, Benzoylation in room temperature ionic liquid. Synth. Commun : 30, 1605-1608 (2000).
9. Hisahiro H, Yumiko S, Takashi H, Toshio S, Masayoshi A, Keisuke O and Chiaki Y, Heterogeneous Heck reaction catalyzed by Pd/ C in ionic liquid. Tetrahedron Lett. 42: 4349- 4351 (2001).
10. Khadilkar BM and Rebeiro GL, Chloroaluminate Ionic Iiquid for Fischer Indole Synthesis. Synthesis 3: 370-372 (2001).
11. Ionic liquids open up vistas. Chemistry & Industry, 16^th April, pp. 231 (2001).
12. Seddon KR, Ionic liquids for Clean Technology. J. Chem. Tech. Biotechnol. 68: 351-356 (1997)
13. Carpio RA, King LA, Lindstrom RE, Nardi JC and Hussey CL, Density, Electric Conductivity, and Viscosity of Several N-Alkylpyridinium Halides and their mixtures with Aluminum Chloride. J. Electrochem. Soc.: Electrochemical Science and Technology 126: 1644-1649 (1979).
14. Wilkes JS, Levisky JA, Robert AW and Hussey CL, Dialkylimidazolium Chloroaluminate Melts: A New Class of Room –Temperature Ionic Liquids for Electrochemistry, Spectroscopy, and Synthesis. Inorg. Chem. 21: 1263-1264 (1982).