Introduction
Oximes have many applications in organic synthesis 1. These compounds have antimicrobial, antioxidant, antitumor, anti-depressive, antiviral agents, and anticonvulsant properties 2-7. Some oximation methods have been reported 8. However our ongoing attentions to the development of new modified methods in organic synthesis 8-15,we have investigated the oximation of a variety of carbonyl compounds with NH2OH·HCl in the presence of BaCl2.
Results and Discussions
For finding optimization reaction conditions bezaldehyde and acetophenone have been used as model compounds. Experiments showed that using NH2OH.HCl (1.2 mmol) and BaCl2 (1 mmol) in C2H5OH (3 ml) was the best conditions for the oximation of benzaldehyde. The reaction was completed within 30 minutes in reflux conditions with the excellent yield (95%) of the product as shown in scheme 1
A variety of aldehydes were ground with NH2OH·HCl/BaCl2 system under optimized reaction conditions. In this approach, the corresponding Z-aldoximes were obtained in quantitative yield (93-98%). The results have been reported in table 1.
Table 1: Oximation of Aldehydes (1 mmol) by NH2OH.HCl (1.2 mmol)/BaCl2 (1 mmol) Under Reflux Conditions in Ethanol (3 mL).
Entry
Substrate
Product
1H chemical shift of C(H)=N(δ ppm)
Time(min) Yield(%)a 1HNMR(δ ppm), IR (cm-1) and m.p. (°C) 7
1
benzaldehyde
(Z)-benzaldehyde oxime
8.18
30, 95 1HNMR (CDCl3) 7.41-7.59 (m, 5H, Ar), 8.01 (bs, 1H, OH), 8.18 (s, 1H, CH). IR (liquid film) 3308 (NOH), 1694, 1497, 1450, 1294, 1073, 958, 756, 691. m.p. –
2
4-bromobenzaldehyde
(Z)-4- benzaldehyde oxime
8.10
35, 95 1HNMR (CDCl3) 5.12 (bs, 1H, OH), 7.27-7.55 (m, 4H, Ar), 8.10 (1H, CH). IR (KBr) 3367 (NOH), 1701, 1589, 1489, 1365, 1067, 968, 703. m.p. 110-112
3b
N,N-dimethylbenzaldehyde
(Z)- N, N-dimethyl benzaldehyde oxime
8.07
40, 96 1HNMR (CDCl3) 3.01 (s, 6H, CH3), 5.31 (s, 1H, OH), 6.69 (d, 2H, Ar), 7.46 (d, 2H, Ar), 8.07 (s, 1H, CH). IR (KBr) 3237 (NOH), 1611, 1447, 1100, 811, 736. m.p. 143-145
4b
4-methylbenzaldehyde
(Z)-4-methyl benzaldehyde oxime
8.15
40, 93 1HNMR (CDCl3) 2.38 (s, 3H,CH3), 7.21 (d + bs, 3H, Ar + OH), 7.49 (d, 2H, Ar), 8.15 (s, 1H, CH). IR (KBr) 3400 (NOH), 1635, 1409, 1265, 1040, 896, 740. m.p. 80-81 Table (1) Continue.
Entry
Substrate
Product
1H chemical shift of C(H)=N (δ ppm)
Time(min), Yield (%)a 1HNMR(δ ppm), IR(cm-1) and m.p.(°C) 7
5b
3-methylbenzaldehyde
(Z)-3-methyl benzaldehyde oxime
8.15
40, 92
1HNMR (CDCl3) 2.38 (s, 3H,CH3), 7.21-7.41 (m, 4H, Ar), 7.82 (bs, 1H, OH), 8.15 (s, 1H, CH). IR (liquid film) 3314 (NOH), 1632, 1584, 1489, 1410, 1309, 1266, 954, 786.. m.p. –
6
4-nitrobenzaldehyde
(Z)-4-nitrobenzaldehyde oxime
8.27
30, 93
1HNMR (CDCl3) 7.76(d, 2H, Ar), 8.23 (d + bs, 3H, Ar + OH), 8.27 (s, 1H, CH). IR (KBr) 3077 (NOH), 1603, 1535, 1348, 1108, 970, 847, 748, 686. m.p. 129-130
7b
2-methoxylbenzaldehyde
(Z)-2-methoxy benzaldehyde oxime
8.49
40, 97
1HNMR (CDCl3) 3.89 (s, 3H,OCH3), 5.97, (bs, 1H, OH), 6.97 (q, 2H, Ar), 7.38 (t, 1H, Ar), 7.68 (d, 1H, Ar), 8.49 (s, 1H, CH). IR (KBr) 3304 (NOH), 1632, 1497, 1449, 1299, 1211, 957, 870, 756, 692. m.p. 75-77
8b
4-methoxybenzaldehyde
(Z)-4-methoxy benzaldehyde oxime
8.11
35, 98
1HNMR (CDCl3) 3.84 (s, 3H,OCH3), 6.92 (d, 2H, Ar), 7.53 (d + bs, 3H, Ar + OH), 8.11 (s, 1H, CH). IR (KBr) 3312 (NOH), 1606, 1514, 1254, 1175, 956,832, 835. m.p. 43-44
aYields refer to isolated pure products(±2%)
Then, the oximation of ketones was also performed well by NH2OH·HCl/BaCl2 system. Experiments showed the oximation of ketones requires higher molar amounts of NH2OH·HCl (1.5 mmol) and BaCl2 (1 mmol) vs. 1 mmol of the substrates. The reaction of acetophenone was completed in 65 minutes with the excellent yield (93%) as shown in scheme 2.
A variety of acetophenones were ground with NH2OH·HCl/BaCl2 system under optimized reaction conditions. In this approach, the corresponding E-acetophenonoximes were obtained in quantitative yield (87-95%). The results have been reported in table 2.
Table 2: Oximation of Ketones (1 mmol) by NH2OH.HCl (1.5 mmol)/BaCl2 (1 mmol) Under Reflux Conditions in Ethanol (3 mL)
Entry
Substrate
Product
1H chemical shift of CH3
(δ ppm)
Time(Sec) Yield (%)a
1HNMR (δ ppm), IR (cm-1) and m.p.(°C) 7
1
acetophenone
(E)-acetophenone oxime
2.34
65, 93
1HNMR (CDCl3) 2.34 (s, 3H, CH3), 7.40-7.63 (m, 5H, Ar), 8.10 (s, 1H, OH). IR (KBr) 3305 (NOH), 1630, 1602,1498, 1446, 1261, 1096, 925, 757, 695. m.p. 54-55
2
4-methylacetophenone
(E)-4-methylacetophenone oxime
2.38
70, 87
1HNMR (CDCl3) 2.31 (s, 3H, CH3), 2.38 (s, 3H, CH3), 6.35 (s, 1H, OH), 7.21 (d , 2H, Ar), 7.54 (d, 2H, Ar). IR (KBr) 3397 (NH), 1636, 1420, 1265, 1095, 817, 739. m.p. 80-81
3
4-methoxyacetophenone
(E)-4-ethoxyacetophenone oxime
2.30
100, 90
1HNMR (CDCl3) 2.3 (s, 3H, CH3), 3.83 (s, 3H, OCH3), 6.91 (d + bs, 3H, Ar + OH), 7.58 (d, 2H, Ar). IR (KBr) 3305 (NOH), 1602, 1446, 1216, 1096, 925, 757. m.p. 79-80
4
benzalacetone
(E)-benzalacetone oxime
2.18
70, 95
1HNMR (CDCl3) 7.28(Ar, 2H), 6.87(Ar, 2H), 4.81 (CH, 1H), 3.78(OCH3, 3H), 2.53 (OH, 1H), 1.45 (CH3, 3H). IR (KBr) 3271 (NOH), 1633, 1448, 1260, 1029, 964, 802, 1034, 749, 691. m.p. 111-113
aYields refer to isolated pure products(±2%).
Experimental
All substrates and reagents were purchased from commercially sources with the best quality. IR and 1H NMR spectra were recorded on PerkinElmer FT-IR RXI and 300 MHz Bruker spectrometers, respectively. The products were characterized by their 1H NMR or IR spectra and comparison with authentic samples (melting points). All yields referred to isolated pure products. The purity of products was determined by TLC and 1H NMR. Also, reactions were monitored by TLCs utilizing plates cut from silica gel 60 F254 aluminum sheets.
A typical procedure for the oximation with NH2OH·HCl/BaCl2 system
In a round-bottomed flask (10 mL) equipped with a condenser, a mixture of benzaldehyde (0.106 g, 1 mmol), NH2OH·HCl (0.084 g, 1.2 mmol) and BaCl2 (0.2 g, 1 mmol) in ethanol (3 mL) was prepared. The mixture was stirred under reflux conditions for 30 min. The progress of the reaction was monitored by TLC. After completion of the reaction, H2O (10 mL) was added and the reaction mixture was continued to stirring for 5 min. The product has been extracted with CH2Cl2 (3х15 mL).The mixture was dried over anhydrous Na2SO4. Evaporation of the solvent and a short column chromatography of the resulting crude material over silica gel (eluent; CCl4/Et2O: 5/2) afforded the pure benzaldoxime (0.115 g, 95 % yield, table 1, entry 1).
Conclusion
The oximation of a variety of aldehydes and ketones was carried out efficiently with NH2OH·HCl/BaCl2 system. The reactions were performed in ethanol under reflux conditions. Excellent yields (93-98%) of products in appropriate times (30-100 min) have been achievement.
Acknowledgements
The authors gratefully appreciated the financial support of this work by Islamic Azad University branch of Mahabad.
