http://www.chemistrymag.org/cji/2003/053025ne.htm

  Mar. 1, 2003  Vol.5 No.3 P.25 Copyright cij17logo.gif (917 bytes)

Reduction of azides to amines with zinc metal in near-critical water

Wang Lei, Li Pinhua, Yan Jincan, Chen Jianhui
(Department of Chemistry, Huaibei Coal Teachers College, Huaibei, Anhui 235000, China)

Received Dec. 16, 2002; Supported by the National Natural Science Foundation of China (No. 20172018), the Excellent Scientist Foundation of Anhui Province (No. 2001040), the Natural Science Foundation of the Education Department of Anhui Province (No. 2002kj254zd), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (No. 2002247) and State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (No.2002-34).

Abstract Zinc metal in near-critical water (250ºC) reduces azides to amines in good yields.
Keywords azides, amines, zinc metal, reduction, near-critical water (NCW)

1 INTRODUCTION             
Organic reactions carried out in water have received much more attention in last decade[1-3]. Unfortunately, the limitation of water as solvent in organic synthesis is its poor dissolving ability for most organic compounds at ambient temperature. On the other hand, the unique properties of water near its critical point (Tc = 374ºC, Pc = 221 bar) have promoted researchers to use it instead of organic solvents in organic synthesis. As water is heated towards its critical point, it changes from a polar liquid to an almost non-polar fluid. Its dielectric constant e decrease from 78.5 at room temperature to 20 at 275ºC, favoring the solubility of organics and ions. Its dissociation constant, Kw, increases several orders of magnitude from ambient to near-critical conditions (Kw = 10¨C11 at 275ºC), providing hydronium and hydroxide ions that can act as the modest acid or base in chemical reactions[4-5]. Although much of supercritical water research has been focused on the total oxidation of organic compounds and geochemical modeling[6-8], there are increasing number of papers which suggest that near-critical water (250-325ºC) used as excellent solvent for organic reactions because organic reactions in near-critical water offer many advantages over those in traditional organic solvents. For example, it is environmentally benign and also easy for the product separation[9,10].
    Amines, widely used as important intermediates in the synthesis of chemicals such as dyes, antioxidants, photographic, pharmaceutical and agricultural chemicals, can be obtained easily from the reduction of azides using catalytic hydrogenation and a variety of other reducing agents with good regio-, stereo- and enantioselectivity. For example, zinc borohydride, samarium-iodine, diboranes, lithium aminoborohydride, iodotrimethylsilane and benzyltriethylaminonium tetrathiomolybdate have been recommended for this transformation[11-13]. However, most of them are carried out in organic solvents, which pose waste handling problems. Because of its low cost and easy availability, zinc has been employed in Barbier-type reaction, C-S coupling, reductive coupling cyclization reaction[14-18]. Here we report the reduction of azides with metallic zinc powder in near-critical water (NCW) at 250ºC, which could generate amines in good yields.

Scheme 1

2 EXPERIMENTAL             
Melting points were measured on a WRS-1A melting point apparatus without calibration. 1H NMR spectra were recorded on a 300 MHz Bruker AZ 300 spectrometer. Chemical shift was given as d value with reference to tetramethylsilane (TMS) as internal standard. IR spectra were obtained by using a Nicolet NEXUS 470 spectrophotometer. The reagents were commercially available without purification prior to use.
    The reduction of azides with metallic zinc in near-critical water was carried out as the following procedure: Azide (1.00 mmol) and metallic zinc powder (196 mg, 3.00 mmol) were added to a stainless steel reactor charged with tap water (10 mL) under nitrogen atmosphere. The reactor was heated and remained at 250ºC for 3 h. After cooling, ether (10 mL¡Á2) was added to extract the products. The organic layer was dried with anhydrous sodium sulfate, then the solvents were evaporated under reduced pressure. The product was purified by flash chromatography to yield amine.
    Aniline£ºOil. 1H NMR (CDCl3): d 7.23 (t, 2H, J = 8.6 Hz), 6.78 (m, 3H), 3.58 (s, 2H); IR (film): nmax 3460, 3362, 1600, 1495 cm-1.
    p-Methylaniline: Mp 43-45ºC. 1H NMR (CDCl3): d 6.98 (d, 2H, J = 8.2 Hz), 6.62 (d, 2H, J = 8.3 Hz), 3.42 (s, 2H), 2.28 (s, 3H). IR (KBr): nmax 3426, 3325, 1609, 1508 cm-1.
    p-Chloroaniline: Mp 67-69ºC. 1H NMR (CDCl3): d 7.04 (d, 2H, J = 8.5 Hz), 6.72 (d, 2H, J = 8.4 Hz), 3.40 (s, 2H). IR (KBr): nmax 3470, 3412, 1600, 1504 cm-1.
    p-Bromoaniline: Mp 62-64ºC. 1H NMR (CDCl3): d 7.23 (d, 2H, J = 8.6 Hz), 6.57 (d, 2H, J = 8.5 Hz), 3.65 (s, 2H). IR (KBr): nmax 3456, 3365, 1614, 1488 cm-1.
    m-Methylaniline: Oil. Bp 199-201ºC. 1H NMR (CDCl3): d 7.02 (m, 1H), 6.56 (t, 1H, J = 8.1 Hz), 6.42 (m, 2H), 3.57 (s, 2H), 2.32 (s, 3H). IR (film): nmax 3416, 3335, 1605, 1503 cm-1.
    m-Chloroaniline: Oil. Bp 220-222ºC. 1H NMR (CDCl3): d 7.04 (m, 1H), 6.72 (t, 1H, J = 7.2 Hz), 6.64 (s, 1H), 6.48 (m, 1H), 3.42 (s, 2H). IR (film): nmax 3456, 3405, 1612, 1514 cm-1.
    m-Acetylaniline: Mp 92-94ºC. 1H NMR (CDCl3): d 7.24 (t, 1H, J = 7.7 Hz), 7.08 (m, 2H), 6.68 (m, 1H), 3.62 (s, 2H), 2.59 (s, 3H). IR (KBr): nmax 3446, 3354, 1659, 1612, 1489 cm-1.
    1-Naphthalenamine: Mp 47-48ºC. 1H NMR (CDCl3): d 7.82 (m, 2H), 7.38 (m, 2H), 7.15 (m, 2H), 6.67 (d, 1H, J = 8.0 Hz), 3.55 (s, 2H). IR (KBr): n max 3458, 3365, 1607, 1502 cm-1.
    1-Dodecylamine: Mp 28-29ºC. 1H NMR (CDCl3): d 2.65 (t, J = 2.06 Hz, 2H), 2.35 (s, 2H), 1.55-1.30 (m, 20H), 0.89 (t, J = 6.80 Hz, 3H). IR (film): nmax 3458, 3365, 1380 cm-1.
    1-Hexadecanamine: Mp 45-47ºC. 1H NMR (CDCl3): d 2.68 (t, J = 2.10 Hz, 2H), 2.40 (s, 2H), 1.57-1.29 (m, 28H), 0.90 (t, J = 6.90 Hz, 3H). IR (KBr): nmax 3462, 3360, 1380 cm-1.
    Safety Warning: This procedure involves a high temperature and pressure and must only be carried out in an apparatus which can stand for the appropriate pressure at the reaction temperature. Meanwhile, the reaction should be performed in a safety place.

3 RESULTS AND DISCUSSION         
Our initial studies were conducted with the aim to explore the reaction conditions for the reduction of azides with metallic zinc powder in hot water. The results are summarized in Table 1. p-Methylphenyl azide was chosen as the model compound for this investigation.
    As seen from Table 1, the reaction temperature has a strong effect on the reduction yield of p-methylphenyl azide with metallic zinc in hot water. It is evident that p-methylphenyl azide could not be reduced to p-toluidine with zinc metal in water at less than 175ºC without any additive. Meanwhile, a moderate yield of reduction product was generated at 225ºC. When the reaction temperature reached 250ºC, a good yield of p-toluidine was obtained. However, the reduction yield of azide decreased significantly as the reaction was carried out in critical water (entry 8, Table 1) because of the unstablility of aromatic amine under reaction conditions[19]. Concerning the effect of zinc mass, the results were shown that if the ratio of zinc to p-methylphenyl azide was less than 2:1, the reduction yield was relatively poor (entries 9 and 10, Table 1). Satisfactory results were achieved while Zn/azide ratio>3:1 (entries 4, 11 and 12, Table 1). Further studies revealed that the reaction was not completed when reaction time was less than 2 h (entries 13 and 14, Table 1). However, no increase of yield was observed when reaction time was increased from 3 h to 4 h or 5 h (entries 15 and 16, Table 1). The optimum reaction conditions for the reduction of p-methylphenyl azide with zinc metal in water were found to be Zn (3 eq.), p-methylphenyl azide (1 eq.), H2O (10 mL), temperature (250ºC), and reaction time (3 h).

Table 1 The reaction conditions for the reduction of p-methylphenyl azide with zinc metal in watera

Entry

Zn:Azide

Temp. (ºC)

Time (h)

Yield (%)b

1

3:1

175

3

0 c

2

3:1

200

3

19

3

3:1

225

3

52

4

3:1

250

3

90

5

3:1

275

3

89

6

3:1

300

3

82

7

3:1

350

3

67

8

3:1

374

3

45

9

1:1

250

3

43

10

2:1

250

3

71

11

4:1

250

3

90

12

5:1

250

3

89

13

3:1

250

1

34

14

3:1

250

2

77

15

3:1

250

4

88

16

3:1

250

5

85

a Reaction conditions: p-Methylphenyl azide (1.00 mmol), tap water (10 mL) in a high T/p batch reactor system. b Isolated yield. c Starting material p-methylphenyl azide (97 %) was recovered.

    A variety of azides were successfully reduced to amines with metallic zinc powder in near-critical water (250ºC). The results were summarized in Table 2. The data in Table 2 indicated that, alkyl azides and aryl azides with either a general electron-donating group (such as CH3) or a electron withdrawing group (such as CH3CO, Cl) on the aromatic ring could be reduced smoothly to the desired amines in good yields with zinc metal in water at 250ºC. No elimination of chloro group was observed. However, bromo or iodo group on the aromatic ring underwent reductive elimination of the Br or I in a competitive process. The reactivity of halogen atoms on the aromatic ring is I> Br> Cl, which is consistent with the expected reactivity of halogen atom in an aromatic ring and Poliakoff's experimental results[20]. Carboxylic group on the aromatic ring also underwent decarboxylation process.

Table 2 Reduction of azides to amines with zinc metal in near-critical watera

Entry

Azides

Amines

Yield (%)b

1

C6H5N3

C6H5NH2

82

2

p-CH3C6H4N3

p-CH3C6H4NH2

88

3

m-CH3C6H4N3

m-CH3C6H4NH2

86

4

m-CH3COC6H4N3

m-CH3COC6H4NH2

89

5

p-ClC6H4N3

p-ClC6H4NH2

90

6

p-BrC6H4N3

p-BrC6H4NH2
C6H5NH2

28c
44c

7

m-ClC6H4N3

m-ClC6H4NH2

80

8

n-C12H25N3

n-C12H25NH2

87

9

n-C16H33N3

n-C16H33NH2

92

10

p-IC6H4N3

C6H5NH2

70

11

p-HO2CC6H4N3

C6H5NH2

72

12

a -C10H7N3

a -C10H7NH2

91

a Reaction conditions: Azide (1.00 mmol), metallic zinc powder (3.00 mmol), tap water (10 mL) in a high T/p batch reactor system at 250ºC for 3 h. b Isolated yield. c Determined by GC and NMR analysis of the reaction mixture.

4 CONCLUSION
In summary, a novel, reliable and practical synthetic method for the preparation of amines has been developed, which involves the reduction of azides by zinc metal in near-critical water. The advantages of the present method are simple, giving good yields and environmentally benign.

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