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Oxidation of Benzylamines toAmidesJ. Hodge Markgraf a , Poorab K. Sangani a & ManuelFinkelstein aa Department of Chemistry, Williams College,Williamstown, MA, 01267-2692, USAPublished online: 22 Aug 2006.

To cite this article: J. Hodge Markgraf , Poorab K. Sangani & Manuel Finkelstein(1997) Oxidation of Benzylamines to Amides, Synthetic Communications: AnInternational Journal for Rapid Communication of Synthetic Organic Chemistry, 27:7,1285-1290, DOI: 10.1080/00397919708003367

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SYNTHETIC COMMUNICATIONS, 27(7), 1285-1290 (1997)

OXIDATION OF BENZYLAMINES TO AMIDES

J. Hodge Markgraf,' Poorab K. Sangani, and Manuel Finkelstein

Department of Chemistry. Williams College Williarnstown, MA 01267-2692, USA

Abstract: A convenient method for the conversion of tertiary benzylamines to benzamidcs by phase transfer oxidation is described. Yields are good. Regioselectivities are reported.

In 1981 Schmidt and Schger reported the homogeneous oxidation of tertiary

amines to amides with benzyltriethylammonium permanganate (BTAP) in

dichloromethane.1 Yields were very good: 72-!93% for trialkylamines and 63-78%

for N,N-dialkylanilines, but unsymmetrical trialkylamines gave product mixtures in

which the ratio of major:minor amides was 1.4-2.4. The one exception was N,N-

dimethylbemylamine which afforded a 1 0 1 ratio of benzamide:formamide and thus

was preparatively useful. Li and Snyder have used BTAP in acetic acid-

dichloromethane to convert canthines to canthind-ones? In a recent study of the

carbocyclic analog of canthind we attempted a similar oxidation under conditions

*To whom correspondence should be addressed.

1285

Copyright 0 1997 by Marcel Dekker. Inc

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1286 MARKGRAF, SANGANI, AND FINKELSTEIN

that circumvented the instability of BTAP: but the product mixture of amide and

enamide was less satisfactory than the pure enamide obtained by Li and Snyder.*

In this paper we report the potassium permanganate oxidation of tertiary

benzylamines under phase transfer catalysis (ptc) in dichloromethane. We assessed

a variety of ptc agents, and the reagent of choice was benzyltriethylammonium

chloride. A reaction time of three hours was sufficient to consume all starting

material. This mild, less hazardous procedure was applied to a wider array of

benzylamines than the one earlier examp1e.l The results are presented in the Table.

Since the regioselectivities exhibited in the present study were comparable to those

observed with BTAP,I the synthetic utility of this method was established for N-

alkyl arylamines and N-methyl benzylamines. The yields were good, except for 6

and 8. The former was not unexpected, since the positions adjacent to nitrogen

were not benzylic. The poor results with 8 can be attributed to the nature of the

heterocyclic ring. Since we recovered only starting material from N-ethylcarhazole

and N-benzylimidazole oxidations, our method proved ineffectual with N-alkyl

n-deficient heterocycles.

Experimental Section

5

Starting materials and products were commercially available or were prepared

by literature methods and purified to the reported physical properties. References

for the latter are included for individual compounds in the Table. Product analyses

were performed on a Hewlett-Packard 589011 gas chromatograph with a SPB-5

polydiphenyl(5%)-dimethyl(95%)siloxane column (30 m x 200 pm with 0.2 pm

film) and Hewlett-Packard 5971A mass spectrometer (EI, 70 eV). Products were

identified by comparison with authentic compounds. Product ratios were

determined in triplicate (*l%) and included detector response calibration factors.

Product yields (*2%) were measured with naphthalene as an internal standard.

Melting points are uncorrected.

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OXIDATION OF BENZYLAMINES 1287

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a w 5 m

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5 d z N" m d

a c3 V

01 c 5' m

$! 8 3:

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6 BnCH2NMq l5 44

7 B n N P k e 96 BzNPh2

8 Bn 3 26 B z G

Table Continued

HCON(Me)CHzBn (2.2) BnCONMg ( 1 .O)

a Ac = acetyl, Bn = benzyl, Bz = benzoyl, Et = ethyl, Me = methyl, Ph = phenyl.

b Combined yields of all products determined by GC with an internal standard.

f2 Prepared by the method in ref. 8.

d -Prepared by the method in ref. 13.

Prepared by the method in ref. 16.

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OXIDATION OF BENZYLAMINES 1289

Oxidation of Amines: General Procedure

To a stirred solution of the amine (1.00 mmol) and benzyltriethylamrnonium

chloride (0.683 g, 3.00 mmol) in dichloromethane (10 mL) was added finely

ground potassium permanganate (0.474 g. 3.00 mmol), and the purple solution

was heated at reflux for 3 h. The purple-brown mixture was cooled in an ice bath

and a solution of sodium bisulfite (2 g) in water (10 mL) was added slowly with

vigorous stirring. The colorless, biphasic mixture was separated, and the aqueous

phase was extracted with dichloromethane (2 x 10 mL). The combined organic

phase was washed with water (15 mL), dried (Na2S04). and concentrated in

vacuo. The residual oil was analyzed directly by GC-MS. Only amides were

observed; no benzaldehyde was detected. The mass spectra of all benzamides

exhibited a characteristic M-1 peak,6 which was not observed with formamides and

acetarnides.

N.N-Dibenzvlbenzamide

To a stirred solution of tribenzylamine (1.44 g, 5.00 mmol) and

benzyltriethylammonium chloride (1.14 g, 5.00 mrnol) in dichloromethane (50 mL)

was added finely ground potassium permanganate (2.3 1 g, 15.0 mmol), and the

purple solution was heated at reflux for 3 h. Work-up as above with sodium

bisulfite (10 g) in water (50 mL), dichloromethane extractions (2 x 40 mL), and

water wash (75 mL) gave residual white solid which was recrystallized from 95%

ethanol to yield product (1.21 g, 81%): mp 112-113 'C (lit.7 mp 112-113 "C).

Acknowledgements

We thank Dr. Jeffrey E. Rowe for a sample of N-benzoyl-N-methyl-

benzamide and Dr. Peter M. Wege I1 for a summer stipend to one of us (P.K.S.)

This work was supported by the Williams College Faculty Research Fund.

References and Notes

1. Schmidt, H.-J.; Schtifer, H. J. Angew. Chem. Inf. Ed. Engl. 1981, 20. 109.

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1290 MARKGRAF, SANGANI, AND FINKELSTEIN

2. Li, J.-H.; Snyder, J. K. Tetrahedron Lett. 1994,35, 1485.

3. Markgraf, J. H.; Finkelstein. M.; Cort, J. R. Tetrahedron 1996,52,461.

4. (a) Jager, H.; Liitolf, J.; Meyer, M. W. Angew. Chem. Int. Ed. Engl. 1979.

18, 786; (b) Schmidt, H.-J.; Schafer, H. J. Angew. Chem. Int. Ed. Engl.

1979,18, 787; (c) Graefe, J.; Rienacker, R. Angew. Chem. Int. Ed. Engl.

1983, 22, 625.

5. Okimoto, T.; Swern, D. J. Am. Oil Chem. SOC. 1977,54,862: salts 1-5 in

Table 1, plus 18-crown-6, were used.

6. Biellmann. J. F.; Hirth, C. G. Orgn. Mass Spectrom. 1969,2, 723.

7 . Franzen, H. Ber. 1909,42, 2465.

8. Barry, J. E.; Finkelstein, M.; Mayeda, E. A.; Ross, S. D. J. Org. Chem.

1974,39, 2695.

9. Lewin, A. H.; Frucht, M.; Chen. K. V. J.; Benedetti, E.; Di Blasio, B.

Tetrahedron 1975.31,207.

10. Ohshiro, Y.; Komatsu, M.; Agawa, T. Synthesis 1971,89.

11. Halman, F. Ber. 1876,3, 846.

12. Wegler. R.; Frank, W. Ber. 1936,69. 2071.

13. Borel, C.; Hegedus, L. S.; Krebs, J.; Satoh, Y. J. Am. Chem. SOC. 1987,

103, 1101.

14. Rowe, J. E. Synthesis 1980. 114.

15. Icke, R. N.; Wisegarver, B. B.; Alles, G. A. Organic Synthesis 1945,25,

89.

16. Agarwal, A.; Agarwal, S. K.; Bhakuni, D. S . Indian J. Chem. 1992,31B,

44.

(Received i n the USA 07 November 1996)

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