J. Chem. Sci. Vol. 129, No. 1, January 2017, pp. 75–80. c Indian Academy of Sciences. DOI 10.1007/s12039-016-1208-8 REGULAR ARTICLE One-pot Reductive Amination of Carbonyl Compounds with NaBH4-B(OSO3H)3/SiO2 in Acetonitrile and in Solvent-free Condition HOSEIN HAMADI∗ and SAMIRA JAVADI Chemistry Department, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran Email: [email protected] MS received 6 August 2016; revised 9 November 2016; accepted 9 November 2016 Abstract. An efficient one-pot procedure for the direct reductive amination of aldehyde and ketones was achieved in the presence of sodium borohydride by using B(OSO3H)3/SiO2(SBSA) as the reusable solid cat- alyst in acetonitrile and solvent-free conditions. Both aromatic and aliphatic aldehyde reacted well to give the corresponding amines in excellent yields. All the products are known and well-characterized. The catalyst is recoverable and could be easily recycled by filtration and reused several times without any significant loss of its activity. SBSA acts as a dual Brønsted/Lewis acid that is an air-stable and cost-effective solid acid. Keywords. Reductive amination; boron trisulfunic acid; catalysis; NaBH4. 1. Introduction a carbon–carbon double or triple bond and other reducible functional groups such as cyano and nitro groups. One of the important method for the synthesis of pri- One of the best reagents for reductive amination is mary, secondary and tertiary amines is the reductive NaBH3CN, which chemoselectively reduces iminium amination of aldehydes and ketones.1 Reductive ami- ions over aldehydes or ketones. However, this reagent nation is a great and trustworthy approach for the for- can liberate hydrogen cyanide when the reaction is mation of C–N bonds, which can avoid the problem quenched, which is highly toxic.6 Another chemoselec- of over-alkylation that often accompanies direct alky- tive reducing agent that has been used is sodium triace- 2 4 lation of amines with alkyl halides. In this reaction, toxyborohydride (NaBH(OAc)3), but it is unstable in an amine and a carbonyl compound condense to afford hydroxylic solvents such as methanol and water.9 an imine or iminium ion in one- or two-step procedure Sodium borohydride (NaBH4) is a safe, green, that is reduced in situ or subsequently to form an amine environment-friendly and inexpensive reducing agent, product. Another problem during reductive amination so it has been the conclusive choice for the direct reduc- of carbonyl compounds with primary amines is over- tive amination process and has been used with vari- alkylation and direct reduction of carbonyl compound ous catalysts.12 However, its application is restricted, in to the corresponding alcohol. In these cases, formation view of the fact that it is accomplished to reduce other and isolation of the imines which followed by reduction reducible functional groups in the molecule. can avoid the problem, but the need to isolate imines NaBH4 is able to reduce imines as well as carbonyls make its synthetic utility poor.5 (aldehydes and ketones) in the same way. To prevent A large number of reducing hydride reagents have the reduction of carbonyl group in the one-pot pro- been studied for direct reductive amination avoiding the cess, the carbonyl-amine condensation reaction must direct reduction of starting carbonyl compound to the be completed before addition of Sodium borohydride. corresponding alcohol, including sodium cyanoborohy- NaBH4 has been used in combination with various 6 7 dride (NaBH3CN), Pyridine–BH3, sodium triacetoxy- catalysts, which assist imine formation, for successful 8 9 13 borohydride (NaBH(OAc)3), hydrosiloxane reagent, reductive amination, such as: Cellulose sulfuric acid, 10 14 15 16 titanium(IV) isopropoxide, and Zirconium (IV) iso- CeCl3.7H2O, SiO2-Zn(BH4)2, Ti(OR)4, wet-clay- 11 17 18 19 20 21 propoxide. However, many of these methods suffer microwave, H2SO4, ZrCl4, NiCl2, H3BO3, sil- 22 23 24 from diverse disadvantages such as toxic compounds ica chloride, micellar media, H3PW12O40, Silica as by-product, hygroscopicity and thermal instability of phosphoric acid,25 Silica-Gel-supported sulfuric acid,26 27 28 29 the reagents, incompatibility with compounds containing Amberlyst 15, DOWEX(R)50WX8, B(C6F5)3, microwave mediated,30 and Ni-complex supported ∗ 31 For correspondence Fe3O4. 75 76 Hosein Hamadi and Samira Javadi HO OH CHCl3 HO3SO OSO3H B ClSO H SiO2 3 HCl B SiO2 BSA OH r.t N2 OSO3H BSA SBSA Scheme 1. Preparation of B(OSO3H)3/SiO2. 1 4 R R 1 R3 SiO2 B(OSO H) R O H N 3 3 N 2 3 r.t 2 4 R R NaBH4 R R CH3CN or Solvent-Free Scheme 2. Reductive amination of carbonyl compounds by NaBH4 cat- alyzed by SBSA in CH3CN and under solvent-free conditions. 32,33 B(OSO H) /SiO (SBSA) is a trifunctional inorga- condition was added NaBH4 (2 mmol, 72 mg), and then the 3 3 2 ◦ nocatalyst that works as a strong acid (soluble in water reaction mixture was stirred at room temperature (25 C) with and polar solvent) which was simply prepared by addi- a magnetic stirrer for 10–20 min. After completion, EtOAc tion of chlorosulfonic acid to boric acid under N (10 mL) was added to the reaction mixture, and the cat- 2 alyst was easily filtered; then, crude product was washed atmosphere at room temperature and then mixed with with H2O (2–10 mL) and a saturated solution of NaHCO3 SiO2 by 1:5 ratio (Scheme 1) and characterized by and dried over anhydrous Na2SO4. After removal of the sol- FT-IR spectroscopy. According to the FT-IR spectra, vent, the pure product was obtained and further purified by the bands at ∼ 1160 cm−1 are related to symmetric recrystallization with a suitable solvent (ether or CHCl3). stretching vibration of O=S=O, and the band centered at 650 cm−1 is related to stretching vibration of S–O. 2.3 Spectral data The band at 1105 cm−1 is attributed to O–Si vibra- tion. The broad and intense O–H stretching absorption The structure of the products was confirmed by FT-IR, 1H, band appears in the region of 3350 cm−1. Due to the 13C NMR, and compared with the corresponding reported 21 29 current challenges for developing green and environ- spectral data. Spectroscopic data for a selected com- mentally benign chemical processes, and using solid pound is presented below: reusable catalyst, we report herein the details of direct reductive amination of aldehydes and ketones using 2.3a N-(4-Nitro Benzyl) Aniline (Table 3, Entry 6): 1H sodium borohydride-B(OSO H) /SiO for the first time NMR (500 MHz, CDCl3): δ 4.51 (s, CH2), 6.63 (d, 2H, 3 3 2 = = = (Scheme 2). J 9.5 Hz), 6.80 (t, 1H, J 9Hz),7.22(t,2H,J 12 Hz), 7.56 (d, 2H, J=11 Hz), 8.22 (d, 2H, 12 Hz); 13C NMR (140 MHz, CDCl3) δ 47.8 (CH2), 113.2 (CH Ar), 118.5 (CH Ar), 123.9 2. Experimental (CH Ar), 127.8 (CH Ar), 129.4 (CH Ar), 146.9 (CH Ar), 2.1 General remarks 147.2 (CH Ar). Chemicals were purchased from Merck and Fluka and used 3. Results and Discussion as received. FT-IR spectra were obtained using BOMEM MB-Series 1998 FT-IR spectrometer. 1H NMR spectra were We started with optimization of the reaction conditions run on Bruker Avance spectrometer (DRX 500 MHz). The by the model reaction of benzaldehyde/aniline at room progress of the reaction was followed with TLC, using sil- temperature. The effects of the reaction conditions, ica gel SILG/UV 254 plates. All the products are known and such as amount of catalyst, reaction time and different were characterized by comparison of their spectra (IR, 1H solvents on the catalytic performance of SBSA were NMR) and TLC with those reported in the literature. examined. Table 1 summarizes the results obtained for different amount of catalyst which shows that the best 2.2 General procedure performance is seen in the presence of 0.05 g amount To a mixture of aldehyde (1 mmol), amine (1.2 mmol) and of SBSA. The results presented in Table 2 point out SBSA (0.05 g) in CH3CN (5 mL) or under solvent-free that the reaction of benzaldehyde and aniline exhibited One-pot Reductive Amination of Carbonyl 77 Table 1. Optimization of the amount of catalyst. As indicated in Table 3, excellent yields were obtained with electron-withdrawing as well as electron- Entry Catalyst (g) Time (min) Yield (%) donating groups (entries 1–8), Functional groups such = 10.151050as –Cl, –Br, –NO2,andC C (Entry 19) present on the 2 0.1 10 68 aldehyde remained unaffected. On the other hand, using 3 0.05 5 85 different amine component with benzaldehyde shows 40.021580that aniline containing an electron-withdrawing group decreases the reaction yield (entry 11), whereas an ani- Table 2. Solvent selection. line containing an electron-donating group increased the product yield slightly (entry 10). Entry Solvent Time (min) Yield (%) Aliphatic and cyclic ketones also undergo reductive amination effectively to give the corresponding amines 1H2O 180 80 2EtOH9070in excellent yields (entries 17–19). In order to illustrate 3CH3CN 10 95 the scope and limitation of this method, we also exam- 4 PEG-300 50 80 ined aliphatic amines such as benzylamine, pyrrolidine 5 THF 120 60 and morpholine, which have shown excellent yields 6CHCl3 180 20 (entries 13, 15–17). All the products are known com- 7 Solvent-free 5 96 pounds and were checked by the 1H-chemical shift of Reaction conditions: 1 mmol benzaldehyde, 1.2 mmol ani- the CH2 group which comes out around 4.22–4.68 ppm line and 2 mmol NaBH4 at room temperature.