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Debenzylation of N-Benzylamino Derivatives byCatalytic Transfer HydrtyationWith Ammonium FormateSiya Ram a & Leonard D. Spicer aa P.E.T. Facility/Nuclear Medicine Department ofRadiology and Department of Biochemistry, DukeUniversity Medical Center, Durham, North Carolina,27710

Version of record first published: 05 Dec 2006.

To cite this article: Siya Ram & Leonard D. Spicer (1987): Debenzylation of N-Benzylamino Derivatives by Catalytic Transfer Hydrtyation With Ammonium Formate,Synthetic Communications: An International Journal for Rapid Communication ofSynthetic Organic Chemistry, 17:4, 415-418

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SYNTHETIC COMMUNICATIONS, 1 7 ( 4 ) , 415-418 (1987)

DEBENZYLATION OF N-BENZYLAMINO DERIVATIVES BY CATALYTIC TRANSFER HYDRTYATION WITH

AMMONIUM FORMATE '

Siya Ram* and Leonard D. Spicer

P .E .T . Facil ity/Nuclear Medicine Department of Radiology and Department of Biochemistry

Duke University Medical Center, Durham, North Carolina 27710

-: A method for deprotection of several N-benzyl derivatives of aminee to the corresponding amino derivatives with ammonium formate and 10% PI-C is reported .

In our studies of efficient and rapid synthetic methods for

radiopharmaceutical molecules labeled with the short-lived

isotope C-11 (half-life = 20.4 m i d , we have developed a

catalytic deprotection procedure for N-benzyl derivatives of

amines which is carried out under neutral conditions. Previous

methods have either involved traditional high pressure catalytic

*To whom correspondence should be addressed.

415

Copyright 0 1987 by Marcel Dekker, Inc.

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41 6 RAM AND SPICER

hydr~genation~'~ orr more recentlyr formic acid as the

hydrogen donore5 The later reaction gives formate salts from

protected 2-amino acid precursors rather than free amino acids

due to the acidic medium of the system. The general type of

catalytic hydrogenation we report has been used successfully for

removal of an 0-benzyl group from peptides using cyclohcxener

1.4 cyclohexadiener hydrazine-hydrate and ammonium formate ae

hydrogen donore. 6-11

Our deprotection method for N-benzyl mines which gives the

free amine directly using ammonium formate i e shown in Scheme 1

(R = H/CH3; B1 = Albyl/Aryl).

SCHEME 1

R HC02NH4 > N-CH2C6H5 10% Pd-C, CH30H, reflux

R1 I

for t h e de- of I t o u: To a

stirred suspension of an appropriate N-beneyl compound ( 3 mmol)

and an equal weight of 10% PI-C in dry methanol (20 mljr

anhydrous ammonium formate (15 mmol) vas added in a single

portion under nitrogen.

stirred at reflux temperature and the reaction was monitored by

TLC. After completion of reactionr the catalyst was removed by

filtration through a celite pad. which was then washed with

The resulting reaction mixture wae

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DEBENZYLATION OF N-BENZYLAMINO DERIVATIVES 41 7

Table 1

Debenzylation of N-bensyl b i n e Derivatives to Corresponding Amino Derivatives

Reaction Relative Rf Derivatives Product 8 Time Yielda Values of N-Benzyl

(BZ=CH c H 1 in Min x Product s b

2 6 5

d C6H5CH2CH2NHBz C 6HsCH 2CH 2N€i 10 90 0 -4

C6HtjWBZ c6H5m2 4 0 76 0074f

HOCH~CH~CH~NHBZ HOCH 2CH 2CH 2 10 95 0.05e

HOCH 2CH 2NHBz HOCH 2CH 2 10 86 O.2gg

10 83 O.lle

10 92 O J l e

(a) Isolated yields are based on the single experiment and yields were not optimized; (b) prodycte were characterized by comparison with authentic samples (IR. H-NMUr TLC and m.p.1; (c) relative R value = distance travelled by product chromatograph/distance travelled by starting material chromatograph. using E Merck silica gel plates; mobile phase: CHC13:Me0Ht58X NH40H; (d) 9:1:3 drops; ( e l 8.5:1.5:3 drops; (f) 9 . 5 : O 0 5 ; (8) 7:3:6 drops.

f

20 ml of chloroform. The combined organic filtrate. on

evaporation under reduced pressurer afforded the desired amino

derivative. Characterization of this new procedure is shown in

Table 1.

Therre results demonstrate a rapid and versatile system for

rennval of an N-benzyl group from a wide variety of compounds

under moderate reaction conditions. It should also be noted that

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418 RAM AND SPICER

this procedure ha8 aleo been ueed euccesrfully in the eyntheeis

of 3-N-methy-l-phenyl-lr3r8-triaeaepiroC4r51 decan-4-one12 from

1-phenyl-1 , 3.8-tr iaeaep iroC4 , 51 decan-4-one , which is a key

intermediate in the eyntheeie of 3-N-methylepiperone.

F t We thank Dr. Richard Ehrenkaufer for helpful dircuaeione. University Medical Center.

This work wae supported by Radiology, Duke

1) Ram. S. and Ehrenkaufer, R.E., Tetrahedron Letterer 1984. 21,

2)

3 )

4)

5)

6) 7) 8)

9) Anwer, M.K., S.A. Khan, S.A. and K.M. Sivanandaiah, K.M.,

10) Anver, M.K. and Spatola. A.F., Tetrahedron Letters. 1981.

3415. Ram, S. and Ehrenkaufer, R.E. Ehrenkaufer, Syntheeie. 1986, 133. Velluz, L., Amiard. G. and Heymee. R., Bull. Soc. Chim. Fr.. 1954, 1012 . Hartung. W.H. and Simonof, R.# Organic Reactione, 1953, VII, 263. El Amin. B., Anantharamaiah. G.. Royer. G. and Mean8.G.. J. Org. Chern.# 1979. &. 3442 . Khan. S.A. and Sivanandaiah, K.M., Syntheeie, 1978. 750 Jackeon, A.E. and Johnrtone. R.A.W., Syntheeie, 1976. 685 . Felix, A.M., Heimer, E.P., Lambroe, T.J., Tzougraki, C. and Meienhofer. J., J. Org. Chem.. 1978. !& 4194.

Synthesis, 1978. 751.

2.2, 4369. 11) Anwer, M.K. and A.F. Spatola, A.F.. J. Org. Chem.. 1983,

3503. 12) Ehrenkaufer, R.E. et al.8 unpublished reeults.

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