Synthesis of Oximes from the Corresponding of Organic Carbonyl Compounds with NH₂OH.HCl and Oxalic Acid

Introduction

Oximeshave been used for the protection and purification of carbonyl compounds in organic synthesis¹.Also,these compounds have antimicrobial^2-3, antioxidant⁴, antitumor⁵, anti-depressive⁶, antiviral agents and anticonvulsant properties⁷.Recently, the oximationmethods have been reviewed⁸by us. The lack of information for the oximation of carbonyl compounds in the presence of oxalic acid and our ongoing attentions to the development of modified methods in organic synthesis ^8-15 encouraged us to investigate this transformation with NH₂OH·HCl in the presence of oxalic acid.So,herein, we describe a convenient method for the oximation of a variety aldehydes and ketones to their corresponding alcohols with NH₂OH·HCl/H₂C₂O₄ system.

Results and Discussions

In order to determine optimization reaction conditions for the oximation of aldehydes and ketones,bezaldehyde and acetophenone have been used as model compounds. The results showed that using NH₂OH.HCl (1mmol) and H₂C₂O₄ (1 mmol) in CH₃CN (3 ml) was the best conditions for the oximation of benzaldehyde. The reaction was completed in 60 minutes with the excellent yield (95%)of the product as shown in scheme 1.

Scheme 1 Click here to View scheme

 

In order to evaluate the generality of the process, a variety of aldehydes were ground with hydroxylamine hydrochloride under optimized reaction conditions. In this approach, the corresponding aldoximes were obtained in quantitative yield (90-95%). The results have been reported in table 1 (entries 1-6).

The oximation of ketones was also carried out well by NH₂OH·HCl/H₂C₂O₄ system, but due to the lower reactivity of ketones relative to aldehydes, the oximation requires higher molar amounts of NH2OH·HCl (2 mmol) and H₂C₂O₄ (2mmol)vs. 1 mmol of the substrates (table 1, entries 7-12).The results showed that using NH₂OH.HCl (2mmol) and H₂C₂O₄ (2mmol) in CH₃CN (3 ml) was the best conditions for the oximation of acetophenone. The reaction was completed in 90 minutes with the excellent yield (95%) as shown in scheme 2.

Scheme 2  Click here to View scheme

 

Experimental

All substrates and reagents were purchased from commercially sources with the best quality. IR and ¹H NMR spectra were recorded on Perkin Elmer 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 of aldehydes with NH₂OH·HCl/H₂C₂O₄system

In a round-bottomed flask (10 mL) equipped with a condenser, a mixture of benzaldehyde (0.106 g, 1mmol), NH₂OH·HCl (0.07 g, 1 mmol)and oxalic acid (0.09 g, 1 mmol)in CH₃CN (3 mL) was prepared. The mixture was stirred under reflux conditions for 60 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 purebenzaldoxime (0.115 g, 95 % yield, table 1, entry 1).

Table 1: Oximation of Carbonyl Compounds (1 mmol) by NH₂OH.HCl/H₂C₂O₄ under Reflux Conditions in CH₃CN (3 mL).

	Table 1. Oximation of Carbonyl Compounds (1 mmol) by NH2OH.HCl/H2C2O4 under Reflux Conditions in CH3CN (3 mL).
	Entry	Aldehydes	Products	Time/min.	Yieldc/%
	1a	benzaldehyde	benzaldehydeoxime	60	95
	2a	4-bromobenzaldehyde	4-bromo benzaldehydeoxime	55	95
	3a	4-nitrobenzaldehyde	4-nitrobenzaldehydeoxime	60	90
4a		4-methylbenzaldehyde	4-methyl benzaldehydeoxime	60	94
	5a	2-methoxylbenzaldehyde	2-methoxy benzaldehydeoxime	60	91
	6a	4-methoxybenzaldehyde	4-methoxy benzaldehydeoxime	60	94
	7b	acetophenone	acetophenoneoxime	90	95
	8b	4-methylacetophenone	4-methylacetophenone oxime	90	93
	9b	benzalacetone	benzalacetoneoxime	90	94
	10b	Benzophenone	Benzophenoneoxime	80	90
	11b	9H-fluoren-9-one	9H-fluoren-9-one oxime	80	91
	12b	cyclohexanone	cyclohexanoneoxime	60	95
	a The reaction has been carried out by NH2OH.HCl (1 mmol)/H2C2O4 (1mmol). bThe reaction has been carried out byNH2OH.HCl (2mmol)/H2C2O4 (2mmol). c Yields refer to isolated pure products (±3%).

 

A typical procedure for the oximation of ketones with NH₂OH·HCl/H₂C₂O₄system

In a round-bottomed flask (10 mL) equipped with a condenser, a solution of acetophenone (0.120 g, l mmol) NH₂OH·HCl (0.14 g, 2mmol) and oxalic acid (0.18 g, 2mmol) in CH₃CN (3 mL) was prepared. The mixture was stirred under reflux conditions for 90 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 withCH₂Cl₂(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 pureacetophenoneoxime (0.128 g, 95% yield, table 1, entry 7).

Conclusion

In this context, the oximation of a variety of aldehydes and ketones was carried out efficiently with NH₂OH·HCl/H₂C₂O₄ system. The reactions were performed in CH₃CN under reflux conditions.This new protocol for the oximation of carbonyl compounds could be a useful addition to the present methodologies.

Acknowledgements

The authors gratefully appreciated the financial support of this work by Islamic Azad University branch of Mahabad.

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