Preparation of 1,1-diacetates from aldehydes by LiBH₄ and Ac₂O in the presence of cation exchange resin

Introduction

Carbonyl functional group of aldehydes has been protected in organic synthesis by the preparation of 1,1-diacetates(gem-diacetates, acylals) from the corresponding aldehydes ^1-2because 1,1-diacetates are stable under neutral, basic and critically controlled acidic conditions. Also, these compounds have been used as starting materials for Diels-Alder reactions ³, Grignard ^4a,Barbier^4b,Prins reactions ⁵,Knoevenagel^6a and benzoin condensation. ^6b1,1-diacetates are also used in the synthesis of chrysanthemic acid^7a,sphingofungins E & F^7b and were utilized as cross linking reagents in cotton². Severalmethods^8-50 have been employed for the synthesis of 1,1-diacetates. These methods have some disadvantages such as use of strong acids, moisture sensitivity, high toxicity, high cost of the reagents, unavailable catalyst, harsh reaction conditions and long reaction times, So, the research for new methods for the preparation of 1,1-diacetates is still of importance. This subject encourages us to investigate the preparation of 1,1-diacetates from the corresponding of aldehydes in continuation of our research programs^51-59. Herein, We now report the results of a parallel investigation for the fast and efficient method for the synthesis a variety of 1,1-diacetates with LiBH₄/Ac₂O in the presence of DOWEX(R)50WX4 as acation exchange resin.Former, NaBH₄⁵⁸ and Zn(BH₄)₂⁵⁹have been proposed as a co-reactant.

Results and Discussion

DOWEX (cation exchange resin) as catalyst has been used for the synthesis of Oximes, ⁵¹ reduction of carbonyl compounds, ⁵² synthesis of cyanohydrins ⁵³ and   reductive-aminationof aldehydes⁵⁴. In this context, we have used it for efficient and facile preparation of 1,1-diacetates by LiBH₄/Ac₂O/DOWEX(R)50WX4 at room temperature.

Benzaldehyde as a model compound has been selected. The reaction of benzaldehyde was carried out in different amounts of LiBH₄, Ac₂O, DOWEX(R)50WX4 and solvents for the selection of proper conditions at room temperature. Different solvents (THF, diethyl ether, CH₂Cl₂, CH₃CN, n-hexane, Ac₂O, THF-Ac₂O, Ac₂O-CH₃CN,…) have been tested.We have observed the reaction was most facile and proceeded to give the highest yield in Ac₂O. The optimization reaction conditions showed that using 1.25 molar equivalents of LiBH₄ and 0.5 g of DOWEX(R)50WX4 in 1 mL Ac₂O were the best conditions to complete the reaction of benzaldehye (1 mmol) to 1,1-benzyldiacetate within 10 min with 93% yields of product as shown in scheme 1.

Scheme 1 Click here to View scheme

 

This protocol was further examined by using various structurally different aldehydes. The corresponding1,1-diacetates were prepared in excellent yields (93-97%) within 10 min as shown in Table 1.

The proposed mechanism for the influence of LiBH₄, Ac₂O and DOWEX has been shown in scheme II.It is appear SO₃H groups on DOWEX (cation exchange resin, strong acid) protonate the carbonyl group of aldehydes (scheme II, step I). So the carbonyl group is more susceptible for Ac₂O attack (scheme II, step II).Also, LiBH₄ can promote the reaction by the hydride attack (scheme 2, step III).

Scheme  Click here to View scheme

 

Cinnamaldehyde as an enal has been converted to the corresponding cinnamylacylal in 95% yield as shown in scheme 3.

Scheme 3 Click here to View scheme

 

The reusability of the catalyst has been checked by using the recovered DOWEX(R)50WX4 from the reactions. The experiments have shown that the recovered catalyst after regeneration(It was stirred in HCl 10-5% for 30-60 min, and then washed with distillated water) could be used like the first.

General

The IR and ¹H NMR spectra were recorded on Perkin Elmer FT-IR RXI, 300 MHz Bruker spectrometers, respectively. The products were characterized by their ¹H NMR, ¹³C NMR or IR spectra and comparison with authentic samples (melting points). All substrates and reagents were purchased from commercially sources with the best quality and used without further purification. All yields referred to isolated pure products.

Table1: The preparation of 1,1-diacetates from aldehydes (1 mmol) by LiBH₄ (1.25 mmol),
Ac₂O (1 mL) & DOWEX(R)50WX4 (0.5 g) at RT.

Table 1. The preparation of 1,1-diacetates from aldehydes (1 mmol) byLiBH4 (1.25mmol), Ac2O (1 mL) &DOWEX(R)50WX4 (0.5 g) at RT.
Entry	Aldehydes	Products	Time(min)	Yields(%)a		m.p.(ºC)b
1	benzaldehyde	1,1-diacetoxy-1-phenyl methane	10	93		44-45
2	4-bromobenzaldehyde	1,1-diacetoxy-1-(4-bromophenyl) methane	10	97		94-95
3	2-chloronzaldehyde	1,1-diacetoxy-1-(2-chlorophenyl) methane	10	95		52-53
4	4-chlorobenzaldehyde	1,1-diacetoxy-1-(4-chlorophenyl) methane	10	95		83-84
5	3-chlorobenzaldehyde	1,1-diacetoxy-1-(3-chlorophenyl) methane	10	97		64-65
6	2,4-dichlorobenzaldehyde	1,1-diacetoxy-1-(2,4-dichlorophenyl) methane	10	97		99-101
7	4-nitrobenzaldehyde	1,1-diacetoxy-1-(4-nitrophenyl) methane	10	96		124-125
8	3-nitrobenzaldehyde	1,1-diacetoxy-1-(3-nitrophenyl) methane	10	95		66-67
9	4-methoxybenzaldehyde	1,1-diacetoxy-1-(4-methoxyphenyl) methane	10	95		65-66
10	3-methoxybenzaldehyde	1,1-diacetoxy-1-(3-methoxyphenyl) methane	10	96		oil
11	2-methoxybenzaldehyde	1,1-diacetoxy-1-(2-methoxyphenyl) methane	10	93		69-70
12	3,4-dimethoxybenzaldehyde	1,1-diacetoxy-1-(3,4-dimethoxyphenyl) methane	10	94		64-65
13	4-methylbenzaldehyde	1,1-diacetoxy-1-(4-methylphenyl) methane	10	94		80-81
14	cinnamaldehyde	1,1-diacetoxy-1-(cinammyl) methane	10	95		83-85
a Yields refer to isolated pure products. b The melting points were compared with the literature.46-50

 

Reaction of benzaldehyde with LiBH₄/Ac₂O/DOWEX(R)50WX4 system, A typical procedure

In a round-bottomed flask (5 mL) equipped with a magnetic stirrer, a mixture of benzaldehyde (0.106 g, 1 mmol), Ac₂O (1 mL) and DOWEX(R)50WX4 (0.5 g) was prepared. Then the LiBH₄ (0.028 g, 1.25 mmol) was added to the reaction mixture and stirred at room temperature. TLC monitored the progress of the reaction (eluent; n-hexan/EtOAc: 9/1). The reaction was filtered after completion within 10 min. After completion of the reaction, the catalyst was filtered and washed with ethyl acetate (15 mL). The combined organic layers were washed with saturated NaHCO₃ solution (3 × 10 mL) and water (10 mL) and then dried over anhydrous Na₂SO₄. The solvent were removed on a rotary evaporator under reduced pressure to give pure product. 1, 1-diacetoxy-1-phenylmethane has been obtained (0.l 93 g, 93% yield, Table 1, entry 1) which was characterized by ¹H-NMR, ¹³C-NMR and FT-IR spectroscopy. ¹H-NMR (CDCl₃): δ 2.14 (s, 6H), 7.41-7.43 (Ar, 3H), 7.52-7.55 (Ar, 2H), 7.69 (s, 1H) ppm; ¹³C-NMR (CDCl₃): δ 20.85, 89.67, 126.65, 128.58, 129.74, 135.40, 169.79; IR (KBr) ν = 3021, 1761, 1373, 1243, 1216, 1009, 767 cm⁻¹.

Conclusion

In this context, we have shown that the LiBH₄/Ac₂O/DOWEX(R)50WX4 system is convenient for the preparation of 1,1-diacetates from aldehydes in high to excellentyields. The reactions were carried out with 1.25 molar equivalents of LiBH₄ and Ac₂O (1mL) in the presence of 0.5 g DOWEX(R)50WX4 at room temperature. Shorter reaction times, easy work-up procedure makes as an attractive new protocol and it could be a useful addition to the present methodologies.

Acknowledgments

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

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