Indian Journal of Chemical Technology Vol. 11, November 2004, pp. 848-852

Phase transfer reaction of potassium superoxide with benzylic methyl and methylene compounds in aprotic medium

Ajay Kumar Shukla & Krishna Nand Singh* Department of Applied Chemistry, Institute of Technology, Banaras Hindu University, Varanasi 221 005, India

Received 4 April 2003; revised received 23 July 2004; accepted 16 August 2004

Tetraethylammonium superoxide, generated in situ by the phase transfer reaction of potassium superoxide and tetraethylammonium bromide, brings about an easy oxidation of a variety of benzylic methyl and methylene compounds under significantly mild reaction conditions, at room temperature.

IPC Code: C07B 33/10 Keywords: Phase transfer reaction, tetraethylammonium superoxide, oxidation, benzylic methyl

Oxidation of benzylic -CH3 and -CH2 groups, is an under the action of poly [N,N-dichloro-4-styrene important synthetic transformation which, depending sulfonamide]17, m-chloroperbenzoic acid18, upon the reagents and conditions, affords alcohols, bismuthate19, sodium periodate catalysed by , ketones or carboxylic acids1,2. Over the manganese porphyrins20, potassium years, wide variety of reagents have been tested and supported on zeolite21, cerium ammonium nitrate22, N- developed. Among lanthanide reagents, cerium (IV) hydroxy phthalimide/cobalt (II)23, and potassium compounds3-6, in particular ceric ammonium nitrate permanganate supported by solid polymeric cation 24 [(NH4)2Ce(NO3)6, CAN], represent the most notable exchange resins . 9-Oxofluorene carboxylic has oxidant7,8. A novel oxidation reaction of benzylic been prepared following a new procedure based on methylene to carbonyl group, in pyrroloacridone or the reaction of 2-acetylfluorene with sodium fluoroacridone ring systems, which are potential dichromate in acetic acid25. Catalytic oxidation of anticancer agents, has been recently observed9. The saturated C-H bonds by tetrabutylammonium combination of ruthenium tetraoxide as catalyst with periodate and manganese porphyrins has also been as primary oxidant is shown to carried out26. A new homogeneous catalyst, based on be effective in the oxidation of aromatic rings. The a chemically modified mesoporous silica gel and system could be improved by the addition of a phase possessing immobilized chromium ions has been transfer catalyst10. Alkyl benzenes may be converted prepared and successfully applied to the oxidation of into their corresponding using sodium alkyl aromatics27. Anodic oxidation of methyl- 28 hypochlorite, RuCl3 and tetra-n-butylammonium naphthalene is also documented . Sodium bismuthate bromide11-13, Fe-Mo oxide14, and also by atmospheric mediated oxidation of several dihydrofluorenes has oxidation15. The triphasic system, formed on mixing been studied29. The oxidation of ethylbenzenes and aqueous hypochlorite/bromide, a hydrocarbon and a other alkyl aromatics by dioxygen catalysed by phase transfer catalyst acts as a powerful catalytic iron (III) tetrakis (penta fluorophenyl) porphyrin is system for the side chain oxidation of alkyl reported30,31. Superoxide induced oxidation of aromatics16. hydrocarbons with labile hydrogen is rather scanty but Suitable alkyl benzene side chains are oxidised at interesting32-34. In view of the above, it was the benzylic position to afford carbonyl compounds considered worthwhile to investigate the behaviour of ______benzylic methyl and methylene moieties under the *For correspondence (E-mail: [email protected]; mild reaction conditions of in situ generated tetra- Fax: 0542-316428, 316925) ethylammonium superoxide (Et4NO2). SHUKLA & SINGH: PHASE TRANSFER REACTION OF POTASSIUM SUPEROXIDE IN APROTIC MEDIUM 849

Experimental Procedure Results and Discussion Materials The oxidation of organic substrates provides routes Potassium superoxide (KO2) and tetraethyl- to a wide range of functionalized molecules. ammonium bromide (Et4NBr) were procured from E. Traditional methods involve the use of large Merck, Germany and were used as received. Dry quantities of poisonous high and low DMF (Aldrich, USA) was stored over molecular reagents. However, the reaction conditions are often sieves prior to use. The substrates o-nitrotoluene (1), harsh, the reagent mixture is corrosive and the p-nitrotoluene (2), 2-methylpyridine (4), 4- chemistry is rarely selective. Environmentally methylpyridine (5), diphenylmethane (6), fluorene acceptable catalytic oxidations that operate under (7), 2-nitrofluorene (8), 2,7-dinitrofluorene (9), 2- moderate conditions in the liquid phase with high benzylpyridine (10), anthrone (11), dihydroanthracene selectivity are clearly desirable. The superoxide ion, (12) and xanthene (13) were commercial products O −. , has recently come to the forefront because of its whereas 2,4-dinitrotoluene (3) was prepared 2 according to a literature report35. The other reagents demonstrated biochemical implications and as a and solvents were of A. R. grade. species of relatively unexplored chemical reactivity. Its ability to function as an oxidizing or reducing Reaction of in situ generated tetraethylammonium superoxide agent, and also its nucleophilic or basic properties, with active methyl and methylene compounds 1-13 have made the chemistry of this radical-anion

General method somewhat enigmatic. With an objective to exploit the −. Potassium superoxide (1.06 g, 0.015 mol) was synthetic potential of O 2 , in organic synthesis, weighed in a dry capped specimen tube under dry present study has been undertaken. nitrogen atmosphere and transferred into a two necked In order to investigate the positional effect of the round bottom flask (150 mL) equipped with a nitro group attached to the benzene ring, reaction of nitrogen inlet and a double surface condenser guarded Et4NO2 with o- and m-nitrotoluene was carried out. with CaCl2 tube. The flask was degassed with dry o-Nitrotoluene provides o-nitrobenzoic acid whereas nitrogen and to it were admitted anhydrous DMF (35 m-nitrobenzoic acid is not obtained from mL) and Et4NBr (1.68 g, 0.008 mol). The mixture was m-nitrotoluene. p-Nitrotoluene, however, yields stirred magnetically for 15 min to facilitate the major p-nitrobenzoic acid. o/p-Nitrobenzoic acids are dissolution of the solids. The substrate 1-13 (0.003 presumed to be formed via the intermediate mol) was finally introduced and the stirring was nitrobenzaldehyde as depicted below: continued at room temperature for 8-12 h till the complete loss of starting material was indicated by TLC. After completion of the reaction, the mixture was treated with saturated solution (20 mL) to decompose the unreacted potassium superoxide. Saturated aq. NaHCO3 solution (20 mL) was added to it and the solution was extracted with The investigation began with an effort to optimize diethylether/dichloromethane. The aqueous phase was the reaction conditions for the oxidation of active then acidified with hydrochloric acid and extracted –CH3/-CH2 group using KO2 and Et4NBr. The Et4NBr with diethylether/dichloromethane. The organic layers has been utilized as a useful alternative to 18-crown-6 were washed with , dried over anhydrous owing to its low cost. The substrate diphenylmethane sodium sulphate, filtered and evaporated to yield the (6) was chosen as a model substrate for the products, which were identified on the basis of optimization process (Eq. 1). physico-chemical and spectral data. Melting points were measured in open capillaries and are uncorrected. IR spectra were recorded on a JASCO FT/IR-5300 spectrophotometer. NMR spectra were run on a JEOL FT-NMR spectrometer FX-90Q and the chemical shifts are expressed as δ/ppm, relative to TMS as internal standard. … (1) 850 INDIAN J. CHEM. TECHNOL., NOVEMBER 2004

A set of initial conditions was selected consisting The products were characterized on the basis of of 1 mmol of substrate 6, 1mmol of KO2 and 1 mmol their melting points, elemental analysis and spectral of Et4NBr for the optimization process under inert data (IR and NMR). atmosphere at room temperature. The first variable 1a: mp 147°C; IR (KBr), ν: 689, 731, 797, 1293, examined was the solvent. Dimethylformamide 1366, 1418, 1490, 1531, 1682, 2400-3200 cm-1; 1H- (DMF) was the solvent of ultimate choice as it led to NMR (DMSO-d6 + CDCl3), δ: 7.8-8.5 (m, 4H, ArH), the desired ketone 6a in 20% yield. The other solvents 12.28 (s, 1H, COOH, D2O exchangeable). such as acetonitrile and DMSO displayed poor results 2a: mp 240°C; IR (KBr), ν: 717, 879, 1281, 1293, or intractable products. The next task was to find the 1312, 1351, 1542, 1608, 1693, 2400-3200 cm-1; 1H best molar ratio of KO2 and Et4NBr over the substrate NMR (CDCl3), δ: 8.2-8.6 (m, 4H, ArH), 12.30 (s, 1H, 6. A series of reactions were examined and the molar COOH, D2O exchangeable). ratio of 5:2.5:1 for KO2:Et4NBr:substrate was found 3a: mp 180°C; IR (KBr), ν: 725, 785, 850, 1360, to be the most effective one. Under the above set of 1450, 1490, 1530, 1675, 2400-3200 cm-1 1H NMR reaction conditions, different benzylic methyl and ; (DMSO-d6 + CDCl3), δ: 7.5-8.0 (m, 2H, ArH), 8.5 (s, methylene substrates 1-13 were allowed to react with 1H, ArH). Et NO in DMF under N atmosphere at room 4 2 2 4a: mp 134°C; IR (KBr), ν: 678, 684, 752, 1294, temperature (Scheme 1). -1 1307, 1343, 1454, 1595, 1608, 1720, 2300-3000 cm ; 1 H-NMR (D2O + DCl+TSP), v: 8.2-8.6 (m, 4H, ArH). 5a: mp 316°C; IR (KBr), ν: 673, 699, 765, 856, 1025, 1232, 1328, 1411, 1713, 2200-2700 cm-1; 1H

Scheme 1 NMR (D2O + DCl + TSP), δ: 8.7 (d, 2H, ArH), 9.2 (d, 2H, ArH). Under the significantly mild reaction conditions of 6a: mp 48°C; IR (KBr), ν: 638, 694, 705, 765, Et4NO2, various substrates viz., o-nitrotoluene (1), -1 1 p-nitrotoluene (2), 2,4-dinitrotoluene (3), 2-methyl- 1281, 1323, 1448, 1594, 1653 cm ; H NMR (CDCl3), pyridine (4), 4-methylpyridine (5), are easily oxidized δ: 7.8-8.6 (m, 10H, ArH). 7a: mp 82°C; IR (KBr), ν: 671, 736, 745, 919, to their corresponding carboxylic acids, viz., o-nitro- -1 1 benzoic acid (1a), p-nitrobenzoic acid (2a), 2,4- 1297, 1450, 1599, 1611, 1714 cm ; H NMR dinitrobenzoic acid (3a), 2-pyridinecarboxylic acid (CDCl3), δ: 7.0-7.75 (m, 8H, ArH). (4a) and 4-pyridinecarboxylic acid (5a) respectively. 8a: mp 222-224°C; IR (KBr), ν: 740, 780, 1075, -1 1 The substrates diphenylmethane (6), fluorene (7), 2- 1335, 1390, 1470, 1520, 1592, 1613, 1705 cm ; H nitrofluorene (8), 2,7-dinitrofluorene (9), 2-benzyl- NMR (DMSO-d6 + CDCl3), δ: 7.2-7.8 (m, 7H, ArH). pyridine (10), anthrone (11), dihydroanthracene (12) 9a: mp 288°C; IR (KBr), ν: 745, 775, 1070, 1330, and xanthene (13) are converted to their ketonic 1380, 1465, 1515, 1570, 1610, 1700 cm-1; 1H NMR compounds, benzophenone (6a), 9-fluorenone (7a), 2- (DMSO-d6 + CDCl3), δ: 7.4-7.90 (m, 6H, ArH). nitro-9-fluorenone (8a), 2,7-dinitro-9-fluorenone (9a), 10a: bp 320°C; IR (KBr), ν: 650, 705, 732, 750, 2-benzoylpyridine (10a), anthraquinone (11a) and 943, 1283, 1322, 1448, 1670 cm-1; 1H NMR (DMSO- (12a) and xanthone (13a) respectively. Table 1 d6 + CDCl3), δ: 7.2-8.10 (m, 8H, ArH), 8.6 (d, 1H, outlines the products along with their respective ArH). yields. In situ preparation of Et4NO2 is achieved in 11a: mp 283-285°C; IR (KBr), ν: 693, 809, 1170, −. -1 1 15 min, as determined by aliquot titration for O 2 1285, 1305, 1335, 1580, 1591, 1678 cm ; H NMR content by oxygen evolution and hydrogen peroxide (CDCl3), δ: 7.60-7.90 (m, 4H, ArH), 8.10-8.45 (m, titration. Generally, 0.03 mole of the substrate was 4H, ArH). allowed to react with Et4NO2 at room temperature 12a: mp 283-285°C; IR (KBr), ν: 693, 809, 1170, -1 1 under inert atmosphere. As the reaction progresses, 1285, 1305, 1335, 1580, 1591, 1678 cm ; H NMR the remaining insoluble KO2 is consumed. Each (CDCl3), δ: 7.60-7.90 (m, 4H, ArH), 8.10-8.45 (m, reaction was monitored by TLC for its completion, 4H, ArH). then quenched with cold saturated aqueous brine 13a: mp 172-173°C; IR (KBr), ν: 671, 758, 1332, solution and worked up to afford the products 1a-13a 1346, 1459, 1481, 1608, 1617, 1657 cm-1; 1H NMR in 8-12 h. (DMSO-d6 + CDCl3), δ: 7.3-8.40 (m, 8H, ArH). SHUKLA & SINGH: PHASE TRANSFER REACTION OF POTASSIUM SUPEROXIDE IN APROTIC MEDIUM 851

Table 1⎯Reaction of in situ generated Et4NO2 with substrates 1-13.

Substrates Products Yield* Substrates Products Yield* (%) (%)

CH3 COOH NO2 NO2 46 65 NO NO2 2 O (8) (1) (1a) (8a)

CH3 COOH

49 O2N 68 O2N NO2 NO2 O (9) NO NO (9a) 2 2 (2) (2a)

CH3 COOH O NO2 NO2 66 N 55 N (10) NO2 NO2 (10a) (3) (3a)

O

N N 53 50 CH3 COOH O (4) (4a) (11) O (11a)

O CH3 COOH

56 34 N N (12) O (5) (5a) (12a)

O O

51 62 O (6) (13) O (6a) (13a)

46 (7) O (7a)

*Isolated mass yields are based on 1-13.

852 INDIAN J. CHEM. TECHNOL., NOVEMBER 2004

All the products exhibited physical and chemical 11 Sasson Y, Zappi G D & Neumann R, J Org Chem, 51 (1986) data consistent with their structures. 2880. 12 Murahashi S I, Angew Chem, Int Ed Eng, 34 (1995) 2443. 13 Sasson Y, Quantar A E A A & Zoran A, Chem Commun Conclusion (1998) 73. The present paper emphasizes the use of 14 Kuang W, Fan Y, Liv C, Chen K & Chen Y, J Chem Res Synop, (1992) 610. tetraethylammonium bromide as an inexpensive and 15 Victor Hugo V C, Isidoro G C, Alfonso H L & Annik V B, J useful alternative to 18-crown-6 for superoxide Phy Chem, 104A (2000) 7847. mediated transformations under mild reaction 16 Clarke J H, Grigoropoulou G & Scott K, Synth Commun, 30 conditions. Despite the availability of numerous (2000) 3731. methods for converting benzylic methyl/methylene 17 Ardeshir K & Ebrahim M, Orient J Chem, 16 (2000) 375. 18 Dawei M, Chengfeng X & Hongqui T, Tetrahedron Lett, 40 group to acid/ketone, the advantages of the present (1999) 8915. procedure are mild reaction conditions, easy work-up 19 Banik B K, Venkataraman M S, Mukhopadhayay C & and no waste problems, particularly under non- Becker F F, Tetrahedron Lett, 39 (1998) 7247. aqueous aprotic conditions. 20 Mohazer D, Tayebel R & Goudarziafshar H, J Chem Res Synop, (1998) 822. 21 Sreekumar R & Padmakumar R K, Tetrahedron Lett, 38 Acknowledgement (1997) 5143. The authors are thankful to AICTE, New Delhi for 22 Cain G A & Drummond S, Synth Commun, 30 (2000) 4513. financial support. 23 Wentzel B B, Donners M P J, Alsters P L, Feiters M C & Nolte R J M, Tetrahedron, 56 (2000) 7797. 24 Joshi P L & Hazra B G, J Chem Res Synop, (2000) 38. References 25 Salmeron-Valverde A, Robles-Martinez J G, Compos- 1 Hudlicky M, Oxidations in Organic Chemistry, ACS Medina A A & Zehe A, Synth Commun, 30, (2000) 3997. monograph 186 (American Chemical Society: Washington 26 Mohazer D & Bagher Z M, J Chem Res Synop, (1998) 556. DC), 1990. 27 Chisem I C, Rafelt J, Shieh M T, Chisem J & James H C, 2 Sheldon R A & Kochi J K, Metal Catalysed Oxidations of Chem Commun, (1998) 1949. Organic Compounds, (Academic Press, New York), 1981. 28 Barba I & Tornero M, Tetrahedron, 53 (1997) 8613. 3 Peterson K P & Larock R C, J Org Chem, 63 (1998) 3185. 29 Banik B K, Ghatak A, Mukhopadhayay C & Becker F F, J 4 Molander G A, Chem Rev, 92 (1992) 29. Chem Res Synop (2000) 108. 30 Evans S & Smith J R L, J Chem Soc Perkin Trans 2, (2000) 5 Nair V, Mathew J & Prabhakaran J, Chem Soc Rev,(1997) 1541. 127. 31 Evans S & Smith J R L, J Chem Soc Perkin Trans 2, (2001) 6 Ho T L, in Encyclopedia of Reagents in Organic Chemistry 174. edited by Paquette L A, 2 (1995) 1025. 32 Ruff E L & Timms N, Can J Chem, 58 (1980) 2138. 7 Laali K, Herbert M, Cushnyr B, Bhatt A & Terrano D, J 33 Top S, Jaouen G & Glinchey M Mc, J Chem Soc Chem Chem Soc Perkin Trans 1 (2001) 578. Commun, (1980) 643. 8 Thyrann T & Lightner D A, Tetrahedron Lett, 37 (1996) 315. 34 Singh K N & Singh S, Bull of Electrochem, (2000) 335. 9 Feng S, Panetta C A & Graves D E, J Org Chem, 66 (2001) 35 Furniss B S, Hannaford A J, Rogers V, Smith P W G & 612. Tatchell A R, in Vogel's Text Book of Practical Organic 10 Skarzewski J & Siedleeka R, Org Prep Proceed Int, (1992) Chemistry, 4th edn (ELBS and Longman: London), 1978, 624. 626.