Tetrahedron Letters,Vol.26,No.

S2,pn 6413-6416,1985 Printed in Great Britain

0040-4039/85 $3.00 + .Oo 01985 Pergamon Press Ltd.

RAPID AND EFFICIENT BeDUCTION OF ALIPHATIC NITRO COMPOUNDS TO AMINES

John 0.

Osby and Bruce

Ganem*

Department of Chemistry, Baker Laboratory Cornell University, Ithaca, NY 14853

Suausary: nitro

The combination to amines

of

NaBH4 with

catalytic Ni8R formed

quantities in situ is

of

NiC18

smoothly

reduces

aliphatic

compounds

in methanol:

the

active

catalyst.

Recent carbon-carbon

advances bond use,

iu the forming

alkylation strategies methods to

of

nitroaliphatic

compounds For

have this or

led

to

several to

new gain

in organic

synthesis.l

chemistry remove nitro far

more widespread While are nitroarenes

improved

must be developed anilines

to modify

groups. fewer reagents

can be successfully compounds

reduced

by many different nitro been groups to

techniques.2 their

known which

reduce have or

aliphatic

corresponding

amines.

Nitroaliphatic lithium methods

traditionally

reduced Only

by high-pressure last few years

hydrogenation.3 have alternative

aluminum hydride4 emerged.6 including laboratory amorphous

aluminum amalgam.5 the use of transfer of

in the

hydrogenation, cobalt(II)-promoted play of metal

and titanium

(II) reagents.8.9
reductions surprising)

Work in our has role shown that

on the mechanism transition metal

NaBE4 and LiAlE4 (and sometimes

borides

an essential alkenes

as heterogeneous several

catalysts types find

in the of

reduction

nitriles, salt-hydride of

and alkyl are

halides.lO known to reduce

Although nitroarenes,ll tems. might nation

diverse we co-lld it

transition

reagents reductions

no published to

example

nitroalkane one of groups.

by such reactive that of

sysborides combi-

Nevertheless, catalyze of nickel

seemed worthwhile reduction of

ask whether nitro

the more highly Here we report a variety ca.

the hydride boride

aliphatic

the

(NiZB)

and NaBH4 in CB30H smoothly compounds in situ to amines by the

reduces within

primary, rt. The process in CH3OD.12

secondary i.s catalytic

and tertiary in boride,

nitroeliphatic which

15 min at of

is prepared

NaBH4 reduction

NiC12

6413

6414

Preliminary could FaBB4 with reduce in

experiments nitrocyclohexane

revealed 1 to 1 to

that

neither

the

boride

alone Bowever the the

nor

boride

under of Ni2B

hydrogen with contaminated of

cyclohexylamine 2 in good &, from yield,

2.12,13 although on

mixtures desired

Cll3OR rapidly amounts

reduced of

product and from

was

variable

dicyclohexylamine likely imine, arose

depending 3,

quantity in situ

preparation 2 and

catalyst. amounts of

Compound

4 most

imine reduction

generated intermediate.

transient

cyclohexanone

a presumed

C6HllN02

[UJA

oo 3

cm

Dimer Typically, ha Kl4. finely of of

seemed

to

be

suppressed of

when NiC12 the results

freshly in

prepared,

finely

divided at Ni2B it were using NaBll4 (see

boride using

was 1.0-1.5 as

used. equiv a very

a sonicated After divided sonicating precipitate. prepared NaBB4-NiCl2 byproducts.12 The following in

solution for

CB3OB was

pre-reduced clumps of

30 min, Eest

first-formed (98:2 with or 2:&l 3-3.5

dispersed 25 mole Table). and

were

obtained of

percent Reductions gave several

catalyst 1 using

this in

fashion,

along

equiv were

2-propanol/water Methanolic preparation

ethanol

considerably (Co2B) failed is

slower to reduce

additional conpcunds.

NaBH4-cobalt of

boride

nitroaliphatic

5-amino-S-methyl-2-heranol

representative.

A 100 ml, roundbottom flask containing NiC12-6A20 (.368g, 1.55 mmol) and CB3OH (30 mL) was sonicated to effect complete sclution, then solid NaBB4 (.176g, 4.65 mmol) was 5-nitro-5-methyl-2-hexanol (.SOOg, added portionwise (CAUTION: frothing). After 30 min, 3.3 mmoll was added in CB30B (2 mL) followed by more solid NaBIl4 (.41Og, 10.9 mmol) over when thin layer chromatography indicated all the a 5 min period. Five minutes later, the reaction mixture was filtered through Celite and nitro compcund had disappeared, the boride rinsed with CB3OB (10 c&l. The combined filtrat.es were eluted onto a 2Omm x 1OOmw Dowex 50(W) column previously equilibrated with CB308. After rinsing with more CB3011 (150 GIL), elution with 1.5 g Nl13 in CB3OB (150 mL) afforded .309g (76%) of product aminoalcohol as a colorless, viscous oil. In porating products the case of less water-soluble amines, the methanol filtrate and carrying out acid-base could be partition isolated simply extraction. by eva-

ACKNOWLEDGKEHENT: Acknowledgment by the American Cheaical and Society, NIR

is

made for

to

the

Donors of this

of

the

Petroleum We also

Fesearch thank

Fund, the

administered

support for

research. of the Cornell

NSF (CHE

7904E25,

PCfl GO186431

(RR020021

support

NMB Facility.

6415

TABLE
Na13H4 - Ni213 Reductions of Nitroaliphatic b Compounds

Reactant

. NO2
L

Product

(Yieldc

Wz
(6SXf

W-WOz

(61%)

02N\,&

(76%)

OzN

X i/ lo

COpH

H2N ,fi

2;4

(64%)

02NPcoz3
02pEM
M_
NH~

Q
H 0 H2N p;M

(50%)

NH, E (69%lf

All reductions were carried out according to the representative procedure on the previous page. Products were identified by comparison with authentic samples, Satisfactory IR, NMR and mass spectra were obtained where possible. for all new compounds. Yields reported are for isolated, pure compounds. Isolated as its HCl salt; lower yields are due to appreciable water solubility of this product. Product stirred 2d at rt in CH OH before workup. 14. We thank Dr. S. Nagarajan for 3 reparing and reducing -

6416

REFERJZNCES AND FOOTNOTES 1. 2. Review: (a) (b) 3. (a) (b) 4. (a) (b) 5. (a) (b) T. ibid -*. (c) (d) 6. 1. 8. 9. 10. For S. J. E. C. D. Seebach, E.W. methods: summary Finkbeiner, M. M.J. Seebach, Stiles, Ream, J. Colvin, R.C. of F. Wade, other J. J. B. Lehr, J. T. Weller, Chimia -* 18. Ref. 505 616 J. 6. (1959). (1963). Orn. 689 Chem., (1978). 41. 153 (1976). 33, 1 273 (1979). (1983).

Hydride-based A comprehensive M. H.L. H. Il. Stiles, B.L.

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Haveanx, Sot. Chem,

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E.W. 8. E.J. Am.

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Tetrahedron Svn. R.S. J. R. Miyaji, H. Kudo, Y.

3415 495

Nitroalkenes (a) (b) S.W. J.O. T. K.

G.W.

Kabalka, 2, Chem.

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843

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11.

(a) (b) (c) (d)

Satoh, Banaya, N. H.

Suzuki,

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Mitsuo, Sasaki,

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nickel in

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well-known

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prepared 2226

ethanol,

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Ahuja,

(1973). catalyzes the possibility Chem., 30 37. heterogeneous could 3552 not (1972). 1985) hydrogenation be overlooked: of nitriles cf T.W. (and Russell, can generate Hay, H2 J.E.

13.

Since from

Ni2B NaBH4),

this
J. in Gre.

R.C.

Cornelius, (Received

USA

September