Microwave-Assisted Efficient and Chemoselective Reduction of aldehydes with Thiourea dioxide

 

Urvashi* and Ranjit Singh Dhillon

Department of Chemistry, Punjab Agricultural University, Ludhiana-141004, Punjab, India

*Corresponding Author E-mail: bhardwajurvashi@gmail.com

 

An efficient, inexpensive and chemoselective method using microwave assisted irradiation with thiourea dioxide for the reduction of aldehydes to the corresponding alcohols has been developed. Under the reaction conditions, reduction of the ketones does not occur and the alcohols from the corresponding aldehydes are obtained, in shorter time over the reported one, in excellent yields.

 

 

INTRODUCTION:

Reduction is one of the most important transformations in organic synthesis that can be achieved with a variety of commercially available reducing agents^1-5 and some of them exhibit chemoselectivity. However, many of these reagents are difficult to handle, or are freshly prepared just prior to their use. It results to constraints for their utility in addition to escalation of their cost and many a time gives poor selectivity. In continuation to our efforts to explore chemoselective reagents^6-10 we have earlier reported a selective reduction of aldehydes in the mixture of aldehyde and ketone by using an inexpensive reagent thiourea dioxide (TUDO), in aqueous- ethanolic solution for 2hr at 90°C¹¹. We became interested to get microwave-assistance to achieve the selectivity for reduction in a shorter time using TUDO as the reducing agent. The microwave-assisted chemical reagents have significant importance for various transformations but there are few reports for its selectivity in reduction process of carbonyl compounds^12-14. There is a considerable amount of interest in thiourea oxides, especially thiourea dioxoide (formamidesulfinic acid or aminomethanesulfinic acid, AIMSA) in chemistry and the chemical industry. TUDO is a commercially available reducing agent ¹² and has vast applications for waste paper processing,¹⁵ wool bleaching,¹⁶ the reduction of ferredoxin, cytochrome C, and methemoglobin,¹⁷ and inactivation and modification of cytidine triphosphate synthase.¹⁸

 

TUDO is also employed to reduce organosulfur compounds (sulfylimines, sulfoxides, disulfides),^19,20 nitrite,²¹ for the synthesis of sulfides, selenides and tellurides from the corresponding diselenides and ditellurides under phase-transfer catalysis.^22,23 Aromatic nitro, azoxy, azo and hydrazo compounds were reduced to the corresponding amines and quinones to hydroquinones with TUDO.²⁴ It has been reported that TUDO is also used for deoxygenation of α, β-epoxy ketones²⁵ and deoxygenation of various heteroatomic N-oxides²⁶. To extend the scope of the TUDO as a selective reagent, we report in this article, the microwave assisted chemoselective reduction of aldehydes in reaction mixture of aldehyde and ketone in a much shorter time of only 5 min using TUDO in aqueous alkali-ethanol system.

 

MATERIALS AND METHODS:

General Procedures. All substrates and reagents were procured from Sigma-Aldrich and SD Fine chemicals and were used without further purification unless otherwise stated. The alcohol products were characterized by comparison with authentic samples: mp/bp, mixed mp (wherever applicable), IR, and ¹H NMR. All yields refer to isolated pure products. Thin-layer chromatography (TLC) plates coated with silica-gel G were used to determine the purity of substrate, products and to monitor the progress of the reaction. The IR spectra were recorded on a Perkin Elmer Model RX-IFT-IR spectrophotometer using KBr pallets. ¹H NMR was recorded on a Brucker AC-300F 300 MHz spectrometer in CDCl₃ using TMS as an internal standard with ¹H resonant frequency of 300 MHz.

 

 

Table 1. Chemoselective reduction of aromatic aldehydes to primary alcohols in the presence of aromatic ketones with thiourea dioxide (TUDO) under microwave conditions

Entry	Reactants	Productsb,c	Molar ratiod	Time (min)e	Yield (%)f	bp/mp* (°C)
						Found	Reported
1		Benzyl alcohol	1:1:1	5	90	204-206	203-205
2		2-Hydroxybenzyl alcohol	1:1:1	5	89	83-85*	84-86*
3		3-Hydroxybenzyl alcohol	1:1:1	5	87	68-73*	69-72*
4		4-Hydroxybenzyl alcohol	1:1:1	5	88	113-120*	114-122
5		2-ChloroBenzyl alcohol	1:1:1	5	88	67-71*	69-72*
6		3-ChloroBenzyl alcohol	1:1:1	5	86	236-238	235-237
7		4-ChloroBenzyl alcohol	1:1:1	5	87	66-70*	68-71*
8		4-Methylbenzyl alcohol	1:1:1	5	85	57-62*	56-61*
9		4-Methoxybenzyl alcohol	1:1:1	5	86	23-26*	23-25.5*
10		Heaxan-1-ol	1:1:1	5	92	154-157	156-157
11		Heaxan-1-ol	1:1:1	5	90	154-157	156-157
12		Butan-1-ol	1:1:1	5	89	118-121*	117-120*

^a The unreacted ketones were isolated in quantitative yield.

^bNo Cannizaro and aldol condensation products were found.

^cProducts were characterized by comparison (mp/bp, TLC, IR, ¹H NMR) with authentic samples.

 ^d TUDO: aldehydes: ketones.

^eAll reactions were irradiated under microwave with 1 min interval for 5 minutes.

^f Isolated yield

 

Table 2. ¹H NMR and IR characterization data for compounds

Product	Name of product	IR (cm-1)	1H NMR (δ CDCl3) (300 MHz, DMSO)
1	Benzyl alcohol	3320, 3030, 2932, 2875, 1497, 1454, 1039, 1018, 736, 698	2.57 (br, 1H, exchangeable with D2O) 4.62 (s, 2H) 7.4-7.15 (m, 5H)
2	2-Hydroxy benzyl alcohol	3440, 3160, 2899, 2757, 2628, 1459, 1256, 997, 753	5.0 (br, 1H, exchangeable with D2O) 4.85 (s, 2H) 6.86-7.22(m, 4H) 9.22(br, exchangeable with D2O)
3	3-Hydroxy benzyl alcohol	3380, 3085, 3064, 2934, 2885, 1592, 1415, 1270, 1240, 1024, 985, 925, 780	4.41 (s, 2H) 5.10 (br, 1H, exchangeable with D2O) 6.62-7.09 (m, 4H) 9.27 (br, exchangeable with D2O)
4	4-Hydroxy benzyl alcohol	3386, 3125, 2966, 2890, 1590, 1519, 1235, 1220, 1200, 1170, 990, 830	4.36 (s, 2H) 4.97 (br, 1H, exchangeable with D2O) 6.7-7.0 (m, 4H) 9.25(br, 1H, exchangeable with D2O)
5	2-Chloro benzyl alcohol	3280, 3080, 2995, 1520, 1090, 1030, 1010, 830	5.25 (br, 1H, exchangeable with D2O) 7.26-7.70 (m, 4H) 4.45 (br, 2H)
6	3-Chloro benzyl alcohol	3355, 3050, 2910, 1490, 1077, 1027, 1000, 835, 799	5.20 (br, 1H, exchangeable with D2O) 7.16-7.40 (m, 4H) 4.45 (br, 2H)
7	4-Chloro benzyl alcohol	3364, 3049, 2900, 1490, 1087, 1027, 1010, 835, 830, 799	2.3 (s, exchangeable with D2O) 4.59 (s, 2H) 7.09 -7.45 (m, 4H)
8	4-Methyl benzyl alcohol	3500, 2900, 1580, 1525, 1450, 1200, 1180, 810, 780	3.65 (s, exchangeable with D2O) 2.34 (s, 3H) 7.11-7.16 (m, 4H)
9	4-Methoxy benzyl alcohol	3617, 2955, 2936, 2836, 1514, 1320, 1250, 1185, 1040, 830	2.40 (br, 1H, exchangeable with D2O) 3.76 (s, 3H) 4.51 (s, 2H) 6.8-7.12 (m, 4H)
10	Heaxan-1-ol	3225, 2810, 2800, 2769, 1450, 1380, 1058, 500	3.65 (br, 1H, exchangeable with D2O) 3.50 (t, 2H) 1.43-1.31 (m, 2H) 0.88 (m, 2H)
11	Butan-1-ol	3350, 3000, 2810, 2790, 1500, 1410, 1100, 990, 700	0.5 (br, 1H, exchangeable with D2O) 1.04 (d, 2H) 1.97-2.07 (m, 2H) 3.00 (t, 3H)

 

General experimental procedure for chemoselective reduction of aldehydes mediated by microwave irradiation

A mixture of a benzaldehyde (10 mmol), acetophenone (10 mmol), thiourea dioxide (10 mmol) and NaOH (20 mmol) was dissolved in the 2 mL of ethanol. This mixture was mixed thoroughly with silica gel (60-120 mesh, 6 g) and was air dried to evaporate the solvent to ensure a solvent free reaction. The dried mixture was taken in a 100 mL borosil beaker sealed with aluminium cap fitted with a pressure and temperature-calibrated Teflon seal and subjected to microwave irradiation in a conventional microwave oven with 160W power for 5 min with regular interval of one minute. After cooling, the product was eluted through a column with ethyl acetate. The distillation of the solvent gave the product mixture of two compounds (TLC), one of which corresponds to unreacted ketone whereas the other is the benzyl alcohol that results after the reduction of benzaldehyde. The two component mixture was chromatographed over a bed of silica gel (60-70 g) using increasing percentage of ethyl acetate in hexane to obtain unreacted ketone followed by the pure benzyl alcohol product. The same procedure was used for reduction of other derivatives of benaldehyde and acetophenone. All the synthesised alcoholic compounds are known compounds and were characterized using analytical techniques such as IR and ¹HNMR. Also the identity of these compounds was establised by comparision of their boiling points or melting points. (table 1, 2).

 

RESULTS AND DISCUSSION:

In the initial test studies it was observed that treatment of an aldehyde (1.0 equiv) with TUDO (1.0 equiv) and ethanol (2 mL) in the presence of NaOH (2.0 equiv), the corresponding alcohol was produced in excellent yield (85-90%) and very short reaction time (less than 5 min) under microwave irradiation (Scheme 1). The results are shown in Table 1.

 

Scheme 1. Reduction of aldehydes using thiourea dioxide

 

In order to check the chemoselectivity of this protocol, we conducted a competitive reaction for the reduction of aldehydes, in the presence of ketones. Thus, a mixture of an aldehyde and a ketone (1:1) was allowed to react with TUDO and ethanol, in the presence of a NaOH under microwave irradiation. After 5 min of irradiation, the aldehyde was completely converted to its corresponding alcohol, while the ketone remained unchanged (Scheme 2).

 

Scheme 2. Reduction of aldehydes in the presence of ketones using thiourea dioxide

 

It has been revealed experimentally that the decomposition of thiourea dioxide follows first order kinetics ²⁷ and rate constant increase with pH of solution. In TUDO monanion, C-N bond is apparently much weaker than the C-S bond.²⁸ We assume that the limiting stage of the process is the decomposition of TUDO and the primary decomposition yields ammonia. The sulfoxylate ion (SO₂^-2) reacts with oxygen to give SO₂^- radical anion which in turn react with oxygen and dimerises, accounts for the reducing properties of TUDO in alkaline medium (Scheme 3).

 

Scheme 3. Decomposition pathway of thioureadioxide

 

CONCLUSION:

TUDO can serve as an efficient reducing agent for chemoselective reduction of aldehydes in the presence of ketones in an ethanolic system under microwave conditions.

 

ACKNOWLEDGEMENT:

The authors thank University Grants Commission (UGC), New Delhi for financial support and Professor and Head department of Chemistry, PAU, Ludhiana for providing research facilities.

 

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Received on 28.01.2013         Modified on 10.02.2013

Accepted on 21.02.2013         © AJRC All right reserved