First and Efficient Method for Reduction of Aliphatic and Aromatic Nitro Compounds with Zinc Borohydride As Pyridine Zinc Tetrah

Journal of the Chinese Chemical Society, 2003, 50, 267-271 267

First and Efficient Method for Reduction of Aliphatic and Aromatic Nitro Compounds with Zinc Borohydride as Pyridine Zinc Tetrahydroborato Complex: A New Stable Ligand-Metal Borohydride

Behzad Zeynizadeh* and Karam Zahmatkesh Chemistry Department, Faculty of Sciences, Urmia University, Urmia 57159, Iran

Pyridine zinc tetrahydroborate, [(Py)Zn(BH4)2], as a new stable ligand-metal borohydride, is prepared quantitatively by complexation of 1:1 zinc borohydride and pyridine at room temperature. This reagent efficiently reduces different aromatic and aliphatic nitro compounds to their primary amines in refluxing THF. In addition, the reduction shows chemoselectivity for aliphatic nitro compounds over the aromatic nitro compounds.

Keywords: Reduction; Zinc borohydride; Nitro compound; Chemoselectivity; Amine.

INTRODUCTION been reviewed. These successes prompted us to prepare 13 [(Py)Zn(BH4)2] and investigate its reducing ability. In our For over forty years, sodium borohydride has been study, we also observed that this reagent efficiently reduces widely recognized as the reagent of choice for the reduction aliphatic and aromatic nitro compounds to their correspond- of carbonyl compounds and acid chlorides in protic solvents.1 ing primary amines in refluxing THF (Scheme I). Over the past decades, the utility of sodium borohydride has been greatly expanded and different techniques and modifi- Scheme I cations have been developed for it to reduce organofunctional groups in various solvents. The preparation and application (Py)Zn(BH4)2, 4 mols RNO2 ¾¾¾¾¾¾¾¾¾® RNH2 of modified borohydride agents in organic synthesis have THF, Reflux, 80-98% been reviewed recently.2 These modifications may involve R: Alkyl, Aryl, Heteroaryl replacement of one or more hydrides with other substituents,3 change of the sodium cation to other metal,4 quaternary am- monium5 and phosphonium6a,b cations, a concurrent cation RESULTS AND DISCUSSION and hydride exchange,7 ligand-metal borohydrides8 and fi- nally combination of the hydride transferring agents with Our literature review has shown that the combination 9 10 metals, metal salts, Lewis acids and solid supports. systems of MBH4 (M=Na, K, Li) and borohydride exchange

Zinc tetrahydroborate, Zn(BH4)2, a stable transition resin (BER) in the presence of metals, metal halides or metal 14 15 16 metal borohydride in ethereal solvents, has found applica- salts such as NaBH4/CoCl2, NaBH4/FeCl2, NaBH4/SnCl2, 11 17 18 19 tions in organic synthesis. However, the requirement of its NaBH4/BiCl3 or SbCl3, NaBH4/CuSO4, NaBH4/Pd/C, 20 21 storage in a cold place puts some restrictions on its uses. Re- NaBH4/Co(pyridyl), NaBH4/copper acetylacetonate, 22 23 cently, new stable modifications of zinc borohydride in the LiBH4(NaBH4)/Me3SiCl, KBH4/Cu2Cl2, Ni2B [NaBH4/ 24 25 26 form of tertiary amino or phosphino ligand complexes such Ni(OAc)2], Ni2B (NaBH4/NiCl2), NaBH4/TiCl4, borohy- 12 27 as polytetrahydro[(1,4-h)pyrazine]boratozinc, [(Pyz)- dride exchange resin; BER/CuCl, CoCl2, PdCl2, Cu(OAc)2 28 Zn(BH4)2]n, (1,4-diazabicyclo[2.2.2]octane)tetrahydrobora- and Ni(OAc)2 are effective for the reduction of aliphatic or 2c,6a tozinc complex, [(dabco)Zn(BH4)2] and mono or (bistri- aromatic nitro compounds. On the application of zinc boro- 6c phenylphosphine)zinc tetrahydroborate, [(Ph3P)Zn(BH4)2], hydride or its modifications for this transformation we can’t

[(Ph3P)2Zn(BH4)2], have been introduced and their applica- find any report. We feel it worthwhile to investigate our tions for the reduction of different functional groups have newly prepared reagent for the reduction of nitro compounds.

* Corresponding author. E-mail: [email protected] 268 J. Chin. Chem. Soc., Vol. 50, No. 2, 2003 Zeynizadeh and Zahmatkesh

(Py)Zn(BH4)2 is stable, easy to handle and is quantita- This reducing agent could be stored for months without tively prepared by complexation of 1:1 zinc borohydride and losing its activity. Characterization by atomic absorption and pyridine in dry ether at room temperature (Equations1&2). gravimetric techniques has been carried out. As shown in Ta- ble 1, a great variety of aliphatic, aromatic and heteroaryl ni- Dry Ether tro compounds are reduced to their corresponding amines ZnCl2 ++2NaBH4 Zn(BH4)2 2NaCl (1) with 4 molar equivalents of the reagent in refluxing THF. Zn(BH4)2 + Pyridine Pyridine.Zn(BH4)2 (2) It is noted that carboxylic acid and amides were re-

a Table 1. Reduction of Nitro Compounds to Their Amines with (Py)Zn(BH4)2 Molar Ratio Entry Substrate Product Time (h) Yield (%)b Reag./Subs.

147.595

24596

34680

441.597

54293

642.295

784.592

8 43.598

98795

10c 4291

11 8 3.1 94

12 4 2 96

13 4 0.25 94

14 4 0.8 94

15 40.6796

a All reactions were performed in THF under reflux condition. b Yields referred to isolated products. c Ac-means acetyl group. Reaction of Nitro Compounds with (Py)Zn(BH4)2 J. Chin. Chem. Soc., Vol. 50, No. 2, 2003 269

Table 2. Comparison Reduction of Nitro Compounds with (Py)Zn(BH4)2 and Some Other Reported Reagents Molar Ratio (Reag./Subs.)a/Time (h)/Yield (%) Entry Substrate Product III28 III17 IV17

1 4(7.5)(95) (5:0.1)(1)(94) (8:1.5)(2)(86) (5:2)(0.5)(90)

2 4(5)(96) ---- (8:1.5)(1.5)(85) (5:2)(0.33)(91)

3 4(6)(80) (5:0.1)(1)(96) (8:1.5)(1.5)(90) (5:2)(0.17)(85)

4 4(2)(93) ---- (8:1.5)(1.5)(95) (5:2)(0.17)(88)

5 4(3.5)(98) (5:0.1)(1)(96) ------

6 4(0.67)(96) (6:0.1)(1)(96) ------

I II III IV (Py)Zn(BH4)2; BER/Ni(OAc)2; NaBH4/BiCl3; NaBH4/SbCl3. a In the case of reported reagents, molar ratios are: NaBH4 or BER/halides or salts/substrate. duced faster than the nitro group; therefore chemoselective mixtures. In a typical example, the selectivity ratio for the re- reduction of such functional groups in the presence of nitro duction of aliphatic nitro compound with respect to the aro- group is feasible. (Entries 6, 7, 10 & 11). On the other hand matic one is 100% (Scheme II). our attempts to selective reduction of this functional group in the presence of carboxylic acid or amido group were unsatis- Scheme II factory under different conditions. The reducing ability of the reagent for the reduction of dinitro groups in the substrates is demonstrated by ready reduction of 2,5-dinitrochlorobezene to the corresponding amine with 8 molar equivalents in refluxing THF (95% yield, Entry 9). Heterocyclic compounds such as 2-chloro-4-nitropyridine that contain a nitro group We also observed that less hindered nitro compounds could also be reduced to their corresponding amine faster are reduced faster, as demonstrated by a competitive reduc- than the aromatic ones (Entry 12). tion reaction between two aliphatic nitro compounds (Scheme A comparison in Table 1, shows that with respect to the III). aromatic and heterocyclic nitro compounds, primary, second- ary and tertiary aliphatic nitro compounds were rapidly re- Scheme III duced to their corresponding amines in excellent yields under reflux condition (Entries 13-15) whereas sodium borohydride-transition metal salts systems18,19,25d for reduction of aliphatic nitro compounds usually give 60-80% yields. This advantage is shown by a comparison in the reduction of 2- methyl-2-nitro butane with (Py)Zn(BH4)2 and BER/Ni(OAc)2 (Table 2, Entry 6). To highlight the limitations and advantages of our Since aliphatic nitro compounds are reduced faster than methods, we list some of our results against those of reported nitroarenes, we decided to investigate the chemoselectivity reagents (Table 2). for the reduction of aliphatic and aromatic nitro compound In conclusion, we have shown that (Py)Zn(BH4)2 is a 270 J. Chin. Chem. Soc., Vol. 50, No. 2, 2003 Zeynizadeh and Zahmatkesh new stable ligand-metal borohydride which easily and effi- ACKNOWLEDGEMENT ciently reduces aliphatic, aromatic and heteroaryl nitro compounds to their corresponding amines. Excellent chemo- The authors are grateful for the partial support of this selectivity was observed for the reduction of aliphatic nitro work by Urmia University Research Council. compounds in the presence of the aromatic compounds. Easy preparation of the reagent, a new potentiality of zinc borohydride for the reduction of nitro compounds, mild reaction Received June 4, 2002. condition, high yield of the products and easy work-up of the reaction mixture, make (Py)Zn(BH4)2 a synthetically useful reagent to the present methodologies for the reduction of a REFERENCES variety of nitro compounds. 1. (a) Seyden-Penne, J. Reductions by the Alumino and Borohydrides in Organic Synthesis; 2th ed., Wiley-VCH, EXPERIMENTAL SECTION 1997. (b) Hudlicky, M. Reductions in Organic Chemistry; Ellis Horwood Ltd., Chichester, 1984. (c) House, H. O. General Modern Synthetic Reactions; 2th ed., Benjamine, Menlo Park, CA, 1972. All products were characterized by a comparison of 1 2. (a) Firouzabadi, H.; Zeynizadah, B. Iranian J. Sci. Tech. their physical data with those of authentic samples (IR, H Trans. A 1995, 19, 103. (b) Firouzabadi, H. The Alembic NMR and mp). All yields referred to isolated products. TLC 1998, 58. 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