Indian Journa] of Chemistry Vol. 40B, Juy 2001 , pp. 579-583

Tetraethylammonium bromide catalysed phase transfer reaction of potassium superoxide with hydrazones and tosylhydrazones

Rajesh Kumar & Krishna Nand Singh*

Department of Applied Chemistry, Institute of Technology, Banaras Hindu University, Varanasi 22 1 005, India

Received 21 September 1 999; accepted (revised) 1 7 July 2000

A variety of hydrazones and tosylhydrazones of carbonyl compounds have been investigated under the mild reaction conditions of potassium superoxide and tetraethylammonium bromide in dry dimethylformamide. As a result, hydrazones are generally transformed to their corresponding azines whereas tosylhydrazones undergo facile fragmentation to give the olefinic products in fairly good yields. The study highlights the use of tetraethylammonium bromide as an efficient and inexpensive catalyst for superoxide studies.

The chemistry and reactivity of superoxide ion, 0"2·, have attracted considerable interest because of its characteristic nature to perform a variety of organic reactions 1 .4. In addition to its novelty for synthetic purposes, the biological implications5.7 of 0"2· have prompted organic chemists to understand its reactivity pattern and mechanism of action.

Superoxide ion is practically available to synthetic chemists either by dissolution of alkali metal salts such as potassium superoxide (K02) or by the electrochemical reduction of molecular oxygen in aprotic solvents8• Potassium superoxide has limited solubility in aprotic non-aqueous solvents and decomposes to molecular oxygen in hydroxylic solvents. Improved solubility and enhanced reaction rates can, however, be achieved by the crown ether complexation9 of K02. In the wake of high cost of crown ethers, the chemists have always been curious to explore an inexpensive and useful alternative. In view of the above, we have made a successful effort to use K02!tetraethylammonium bromide (E4NBr) combination in lieu of K02!crown ether for superoxide studies 10, 1 1 .

Our preliminary observation on the reaction of electrogenerated 0"2· with limited hydrazones l2 was reported with the remark to pay more attention in this direction. With an objective to refrain from the use of electrochemical method owing to the difficulty in obtaining high concentration of 0"2· for efficient product studies and also due to the non-availability of electrochemical equipments to common organic chemists, we present herein a detailed and systematic study on the reaction of conveniently generated

tetraethylammonium superoxide (E4N02) with a variety of hydrazones and tosylhydrazones. The present study has been undertaken to reveal the reactivity pattern and synthetic scope of 0"2· in organic transformations.

There is considerable interest in the development of mild techniques for the conversion of hydrazones 13. 14

and tosylhydrazonel5, 16 as they have been employed as ketone and aldehyde functional group equivalent in organic synthesis both as protecting groups as well as synthetic intermediates. Their deprotection is also an useful transformation i n organic synthesis. The oxidation of hydrazones by various metal oxides such as HgO, Ag20 or Mn02 primarily leads to diazoalkanes with azines as a side productI7• 19 . The use of metal oxides has got its inherent disadvantages in terms of high cost, difficulties in the preparation of active metal oxides and problems of waste disposal. The present investigation, employing E4N02, offers an useful alternative methodology which may eliminate these difficulties. The reaction of tosylhydrazones have also been widely studied2o, a classical method being that of Bamford & Stevens 2 1 , utilizing strong basic conditions. Considering the apparent effective basicity of 0"2· to abstract a proton4,22 from substrate having pKa � 24, the reactions of hydrazones and tosylhydrazones with E4N02 have been accomplished.

Various hydrazones viz., acetophenone hydrazone 1, benzophenone hydrazone 2, 4,4'-dimethoxy­benzophenone hydrazone 3, 4,4'-dichlorobenzo­ph en one hydrazone 4, 4,4'-bis(dimethylamino)­benzophenone hydrazone 5, 9-flourenone hydrazone 6, camphor hydrazone 7, benzil monohydrazone 8 and

580 INDIAN J CHEM. SEC. B. JULY 2001

different tosylhydrazones viz., benzophenone tosylhydrazone 9, benzaldehyde tosylhydrazone 10, 4-methoxybenzal-dehyde tosylhydrazone 11, 4-dimethylaminobenzaldehyde tosylhydrazone 12, cyclohexanone tosylhydrazone 13, 2-methylcyclo­hexanone tosylhydrazone 14, benzil monotosyl­hydrazone 15 were subjected to the reaction with in­situ generated Et4N02 (K021E4NBr in OM F) under inert atmosphere at room temperature. The reaction was not optimised for the molar ratio of the reactants. However, an excess of K02 and E4NBr over the substrates afforded better product yields. Typically, the reaction was performed using 4 times molar excess of K02 and 2 times molar excess of E4NBr relative to the substrate 1-15 and monitored by TLC for its completion. The reaction mixture was then quenched and worked up to yield the product la -15a.

Under the mild reaction conditions of Et4N02, the hydrazones 1-7 are readily oxidised to their corresponding azines in fairly good yields whereas benzil monohydrazone 8 gives deoxybenzoin 8a as the only isolable product. Tosylhydrazones 9-15, under the same set of reaction conditions, are cleaved yielding products 9a-15a. The results are summarised in Table I. In some cases, however, TLC indicated the presence of a few intractable products which were not isolable. The above transformations are based on the ability of 0"2· to abstract a weakly acidic proton from the substrate. A plausible mechanism for the transformation of hydrazones may be found in our earlier reportl2. The formation of products 9a-14a may be rationalised in terms of steps depicted in

Scheme I. The abstraction of proton by 0"2· leads to the formation of an anionic species A. This intermediate A successively looses Ts and N2 giving rise to a carbene intermediate C which is ultimately converted into the product 9a-14a. The physical and spectral data (Table II) are in ful l agreement with the product structures. The IR spectra was observed in the range 4000-650 cm· l . In general, the strong bands observed in the region 3400-32 10 cm- I attributable to N-H stretching exhibited by hydrazones and tosylhydrazones was absent in the products. In addition, the products 9a-15a also lacked the medium intensity band at 1 350 and 1 1 50 characteristic of symmetric and assymetric S02 vibrations. In the PMR spectra, the signal in the range cS 4.0-5.0 and cS 8 .5-9.0 due to N-H proton for hydrazones and tosylhydrazones respectively was found absent.

Thus, the use of tetraethylammonium superoxide is advantageous owing to the simplicity of operations involved, conditions and product selectivity.

Experimental Section Melting points were determined in open capillaries

and are uncorrected. IR spectra were recorded on JASCO FTIlR spectrophotometer (vmax in cm·l ) and IH NMR spectra on a JEOL FX-90 Q spectrometer (cS/ppm relative to TMS as internal standard).

Potassium superoxide (K02) and tetraethyl­ammonium bromide (E4NBr) were purchased from E Merck, Germany and were used as received. Oimethylformamide (OMF) obtained from Aldrich, USA was dried over 4A molecular seives prior to use. The starting materials acetophenone, benzophenone,

/ f-.tN-NH-TS / NN-�-TS RIR�=N-NH-Ts 1/ + 6i -- RIR�==N-�-Ts � + H02

[A]

[A]

13a,14a

Scheme I

RAJESH KUMAR et al. : REACTION OF POTASSIUM SUPEROXIDE WITH HYDRAZONES

Table I-Reaction of in-situ generated ElIN02 with hydrazones and tosylhydrazones

Substrate

C6H5,

CH{OC=NNH2

(1)

C6Hs'C=NNH2 C6Hs ...... (2)

(CH30C6I-4hC= NNH2 (3)

(CIC6l4hC= NNH2 (4)

(Me2NC6l4hC= N N H2

(5)

NNH2

� (6)

c1rNNH2

(7)

NNH2 0 " " C6HS-C--C-C6HS

(8)

(C6HshCH=NNHTs (9)

C6HSCH=NNHTs (10)

CH3OC6I-4CH=NNHTs (11)

Me2NC6I-4CH=NNHTs (12)

NNHTs

6 (13)

CH3

ONNH2

(14)

Product

C6Hs, ..... C6HS C=N -N=C

H C..... 'CH 3

(la) 3

C6Hs, ..... C6HS ...... C=N -N=C,

C6HS (2a) C6HS

(CH3OC6H.tnC=N -N=C(C6H.tOCH3n (3a)

(CIC6�hC= N -N =C(C6�Clh (4a)

(Me2NC6l4hC= N -N =C(C6f4NMe2h (Sa)

�N-N�

(6a) (jrN-Nm (7a)

0 II

C6H�CH2C-C6H5 (8a)

C6Hs, .... C�s /C=C,

C�5 (9a) C�s

C6Hs, .... H C=C

H.... 'c H (lOa)

6 �

CH30C�CH=CHC6I40CH3 (l1a)

Me2NC6I4CH=CHC�NMe2 (12&)

0 (13a)

6 (14a)

Yield* (%)

83

75

68

62

7 1

67

54

66

73

7 1

62

59

75

54

58 1

Contd.

582 INDIAN J CHEM, SEC. B, JULY 2001

Table I-Reaction of in-situ generated Et4N02 with hydrazones and tosylhydrazones-Contd

Substrate

*Isolated mass yield based on substrate as weight %_ Ts = p-CH3C6H4SOZ

Product

o I I C6HsCH2CC6HS

(15a)

Yield* (%)

68

Table I1-Characterisation data of compounds la-15a

Compd Found Reported25-2B

'H-NMR (o/ppm)

la 1 19 2a 158 3a 122

1 24 16 1

1 24-25

1655 (vCN), 1600, 1575, 1490 1605 (vCN), 1455, 1 385,765 1 6 1 3 (vCN), 1 3 17, 1 26 1 , 843

U(s, 6H, 2 CH3), 7.2-7.3(s, IOH, Ar-H) 7 . 1 -7A(m, 20H, Ar-H) 3.6(s, 1 2H, 4 OCH3), 6.8-7. I (d, 8H, Ar-H), 7.5�7.7(d, 8H, Ar-H)

4a Sa

223 254

224 253

1620 (vCN), 1584, 1 285, 1090, 728) 1580 (vCN), 153 1 , 1 320, 1 174, 767)

7.3-7.6 (m, 16H, Ar-H) 2.8 (s, 24H, CH3), 6.5-6.7 (d, 8H, Ar-H), 7.6-7.7 (d, 8H, Ar-H)

6a 267 7a 1 8 1 8a 59 9a 225

265 1 82 60

224-26 1 24

2 14- 15

1660 (vCN), 1560, 1450, 1297, 745 1690 (vCN), 1448, 1 39 1 , 1022, 75 1 1686 (vCO),1448, 1 338, 1 202, 752 1600, 1580, 1500, 1450

7.0-7.5(m, 16H, Ar-H) 0.8-204 (complex m, 32H) 4.2 (s, 2H, CH2), 7.2-8. 1 (m, I OH. Ar-H) 6.9-704 (s, 20H, Ar-H)

lOa 1 23 1 1a 216

12a 220

16 10, 1575, 1430 1600, 1575, 1500, 1430

1605, 1575, 15 10, 1450

7.2 (s, 2H, C=C-H), 7.3-7.7(m, I OH, Ar-H) 3.70 (s, 6H, 2 OCH3), 6.9(s, 2H, CH=CH), 7.2-7.6(dd, 8H, Ar-H) 3 . 1 (d, 1 2H, -N(CH3h), 6.9(m, 2H, CH=CH), 7 . 1 -7.7 (dd, 8H. Ar-H)

13a (8 1 ) (8 1 ) 3023, 292� 2859, 1438, 1 1 37, 9 16 1 04- 1 .7 (m, 4H, 2 CHz), \ .8-2. 1 (m, 4H, 2CHz), 5.6-5.8 (m, 2H, 2 CH)

14a ( 1 10) ( 1 10- 1 1 ) 1 650, 1440, 1 330, 1030, 900 1 .6(s, 3H, CH3)' 1 .7-2. I (m, 8H, H,CHz), 5A(s, IH . C=CH)

15a 58 60 1680 (vCO), 1 600, 1580, 1500, 1450 4.3(s, 2H, CHz), 7A-8.2(m, IOH, Ar-H) Boiling points under atmospheric pressure_

4,4'-dimethoxybenzophenone, 4,4'-dichlorobenzo­phenone, 4,4'-bis( dimethy lamino )benzophenone, 4-methoxybenzaldehyde, 4-(dimethylamino) benzalde­hyde, camphor, flourenone, benzil, cyc1ohexanone and 2-methylcyc1ohexanone were of AR grade and used after recrystallisation or fresh distillation.

Hydrazones were prepared by adopting the literature procedure23. Tosylhydrazine, obtained by the reaction of tosylchloride with hydrazine hydrate24, on refluxing with equivalent quantity of substrate in ethanol for 4-6 hr, afforded tosylhydrazone derivatives20. 2-methylcyc1ohexanone tosylhydrazone

15 was prepared by refluxing the components in 1 : 1 mole ratio with a few drops of glacial acetic acid in ethanol followed by addition of water.

Reaction of tetraethylammonium superoxide with hydrazones and tosylhydrazones. K02 (8mmol ; 0.568g) was weighed under inert atmosphere and transferred into a two necked round bottom flask equipped with nitrogen inlet and double surface condenser guarded by CaCI2 tube. E4NBr (4mmol ; 0.64g) and DMF (40 mL) were added and the mixture was stirred magnetically for 1 5 min to facilitate major dissolution of the solids. The substrate 1-15 (2 mmole) was finally admitted to the reaction mixture

RAJESH KUMAR et al. : REACTION OF POTASSIUM SUPEROXIDE WITH HYDRAZONES 583

and stirred at room temperature for about 2.5 to 6 hr. Nitrogen was flushed throughout the course of reaction to remove atmospheric moisture. After the reaction was complete (as checked by TLC) saturated aqueous NaCI solution was added to destroy the excess K02. The mixture was then extracted with ether (3x30 mL). The etheral layer was washed with H20 (2x 1 5 ml), dried over Na2S04, filtered, evaporated and the residue purified to give product la-15a. The structure of products were elucidated on the basis of spectral and physico-chemical data.

Acknowledgement The authors are thankful to UGC and AICTE, New

Delhi for financial assistance.

References 1 Afanas'ev I B, Superoxide ion : Chemistry and biological

implications (CRC Press, Boca Raton, Florida), Vol. I , 1989; Vo1 2, 1991

2 Frimer A A, in the Chemistry of enones, Part 2, edited by S Patai & Z Rappoport (Wiley, Chichester), 1989, pp. 78 1 -92 1

3 Frimer A A, ill the Chemistry of peroxides, edited by S Patai (Wiley, Chichester), 1983, pp. 429-461

4 Sawyer D T & Valentine J S, Acc Chern Res, 14, 1981, 393 5 Frontier of reactive oxygen species in biology and medicine,

edited by K Asada & T Yoshikawa (Excerpta Medica, Amsterdam), 1994

6 Superoxide Disrnutase, edited by L W Oberley (Chemical Rubber Company, Boca Raton, Florida), Vol 1 & 2, 1982; Vol 3, 1985.

7 Fridovich I, Science, 201 , 1978, 875 8 Sawyer D T & Robert (Jr) J L, J Electroanal Chern, 1 2,

1966, 90 9 Valentine J S & Curtis A B, J Am Chern Soc, 97, 1975, 224

10 Kumar R , Singh M & Singh K N, Indian J Chern Teclmol, 5 , 1998, 227

I I Singh S & Singh K N, Indian J Chern, 37B, 1998, 88 1 2 Singh K N, Singh M & Mishra R A, Indian J Chern, 33B,

1994, 85 1 3 Hajipour A R , Mohammadpour B I & Kianf G ,Bull Chern

Soc Jpn , 7 1 , 1998, 2655 14 Shim S B , Kim K & Him Y H ,Tetrahedron Lett. , 28, 1987,

645 15 Adlington R M & Barrett G M ,Acc Chern Res , 1 6, 1983, 55 16 Bose D S & Srinivas P, Synlett , 1998, 977 1 7 Baltzby R , Mehta N B, Russell R B , Brooks R E, Grivishky

E M & Steinberg A M, J Org Chern, 26, 1961, 3672 1 8 Schroeder W & Katz L, J Org Chern, 1 9, 1954, 7 1 8 1 9 Murray R W & Trozzdo A M, J Org Chern, 26, 1961, 3 1 09 20 Shapiro R H, Org React, 23, 1975, 405 2 1 Bamford W R & Stevens T S, J Chern Soc, 1952, 4735 22 Monte W T, Baizer M M & Little R D, J Org Chern, 48,

1983, 493 1 23 Farnum D G, J Org Chern, 28, 1963, 870 24 Friedman L, Little R L & Reichle W R, Org Synthesis, 40,

1960, 93 25 Szmant H B & Mcginns C, J Am Chern Soc, 72, 1950, 2890 26 Wilt J W & Wagner W J, J Org Chern, 29, 1964, 2788 27 Krapcho A P & Dum R, J Org Chern, 30, 1965, 641 28 Dictionary of organic compounds, 4th Edn, Vol 1 ,2 and 3

(Eyre & Spottiswoode Ltd., London) 1965, pp 1 2, 348, 543, 836, 1 140, 1 844.

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