Gallium(III) chloride: an efficient catalyst for facile preparation of gem -diacetates from aldehydes

An efficient, facile preparation of gem -diacetates or diacetoxy acetals from aldehydes in excellent yields, catalyzed by GaCl 3 , under solvent-free conditions, is described herein.


Introduction
Selective protection of carbonyl function as gem-diacetates (acylals) or gem-bis(acyloxy)alkanes is an important transformation in organic chemistry 1 as an alternative to acetals because of their stability under neutral and basic conditions 1b as well as under critically controlled acidic conditions.Apart from mere protective groups acylals are important synthons and are useful precursors.The acylals derived from α-β unsaturated aldehydes are important starting materials for Diels-Alder reactions. 2These gem-diacetates have several synthetic as well as industrial applications.In industries, diactetates are utilized as cross linking reagents 3 in cellulose and cotton industry, being also used as stain bleaching agents.As synthons, acylals have been exploited in well known reactions of organic chemistry, like Grignard, 4 Barbier, 4b and Prins 5 reactions, condensation reactions of Knoevenagel, 6a and benzoin 6b type, and are also used in the synthesis of chrysanthemic acid, 7a and the total syntheses of sphingofungins E and F. 7b Because of their synthetic and industrial utility and unique properties as protective groups as well as important synthons, a search for efficient and facile preparation of acylals is of current interest.Apart from other methods, conventionally gem-diacetates are prepared from aldehyde, acetic anhydride and a catalyst viz strong Bronsted acids 8 like H 2 SO 4 , H 3 PO 4 , and super acids 9 like Nafion-H and heteropolyacids.The use of strong Lewis acids 10 like BF 3 , PCl 3 , ZnCl 2 , LiBF 4 , ZrCl 4 , Er(OTf) 3 , FeCl 3 , FeCl 3 /SiO 2 , Zn(ClO 4 ) 2 .6H 2 O, etc have also been reported.In addition to these catalysts, graphite, zeolites, tungstosilicic acid and zirconium sulfophenyl phosphonate have also been employed in this protection process. 11Some of these methods still suffer from drawbacks like prolonged reaction time (viz.up to 120 h in case of 2-furyl aldehyde with PCl 3 ), low yields in the cases of 4-nitrobenzaldehyde (4 %) and cinnamaldehyde (30 %), when PCl 3 , is used and, in some cases, requirement of elevated temperature.Moreover, several of these catalysts are unsafe to handle, like metal perchlorates, BF 3 , etc. Consequently it seems desirable and necessary to develop a simple, safe, efficient and facile method for the preparation of these gem-diacetates.
Though indium and gallium both are in same group i.e.IIIA, indium and its salts have been studied extensively and the results of this prolific exploration are reviewed from time to time, 12 while gallium and its salts remained almost ignored.Yet, the comparable ionization potentials ( Ga: FIP, 5.99 eV, E o , Ga +3 /Ga = -0.56V; In: FIP, 5.79 eV, E o , In +3 /In = -0.345V ) indicate they should have equally attractive properties.Very recently, the use of gallium is reported in some major reactions of organic chemistry like Reformatsky, 13 Barbier, 14 Grignard, 15 bromination of aromatics 16a and allylation of indoles.16b The applications of gallium(III) halides are developing 17 at a very fast pace, showing that its utility can match indium. 18

Results and Discussion
In continuation of our own work 19 on the use of gallium and its salts, in this communication we wish to report a gallium(III) chloride catalyzed preparation of gem-diacetates, from aldehyde and acetic anhydride (Scheme 1).

Scheme 1
In initial experiments, we used varying quantities of catalyst, viz.from 1 mol% to 20 mol% (Table1).Indeed, we were able to establish the optimum quantity of the catalyst at 5 mol%.In a pilot experiment, p-tolualdehyde, acetic anhydride, and GaCl 3 (1:1.5:0.05), in dichloromethane (Method A), were stirred at room temperature for 3 min to obtain gem-diacetate in 98 % yield.
To show the wide application of this procedure, other aldehydes were reacted analogously to afford gem-diacetates in 80-98 % yields.Under these conditions, reaction time was reduced dramatically and reaction completes within 3-14 minutes (Method A, Table 2).After this success we looked for further improvements in this process, viz. to carry this reaction under solvent-free conditions, at room temperature.(Method B).Under solvent-free conditions, equivalent results were obtained and reaction times shortened to 1-6 minutes, affording gemdiacetates in 82-98 % yields.
ARKAT USA, Inc.A variety of aromatic, aliphatic and heterocyclic aldehydes are converted to corresponding gem-diacetates using acetic anhydride in the presence of GaCl 3 , in excellent yields, at room temperature, and in very short reaction times.All aromatic aldehydes carrying electron-donating or electron-withdrawing substituents reacted well, however, as one can see from Table 2, yields are slightly lower in aromatic aldehydes with electron-withdrawing groups and in case of conjugated aldehydes, particularly for crotonaldehyde and acrolein (entry 10-11, Table 2).This decrease in the yields may be due to the formation of polymeric materials as side products, which is to be expected.To show the selectivity/chemoselectivity of the reaction, it was performed using a mixture of aldehydes and ketones, from which only aldehyde diacetates were obtained (Scheme 2), the ketones remaining unaffected, as illustrated by acetophenone and benzophenone (entries 13-14, Table 2).Furthermore, when aldehyde and ketone groups are present in the same molecule, only the aldehyde diacetate was obtained, the ketone moiety remaining intact (Scheme 3).When this reaction was extended to 3-formyl benzopyran-(4H)-4-one, its formyl diacetate was obtained in excellent yields (Scheme 3).

Conclusions
In conclusion, the present method is a very simple, mild, efficient and convenient catalytic method for the preparation of gem-diacetates from aldehydes under solvent-free conditions using ARKAT USA, Inc. GaCl 3 .In addition, this protocol has advantages in term of short reaction times, high yields, high selectivity, fairly wide scope and avoidance of rigorous reaction conditions.

Experimental Section
General Procedures.IR spectra were obtained with a Perkin-Elmer 237B infra red spectrometer, from KBr pellets. 1 H NMR spectra were recorded in FT-NMR-AL300 spectrometer using tetramenthylsilane (TMS) as internal standard.GaCl 3 used was commercial grade and was not further purified.Acetic anhydride was distilled prior to use.

General procedure for the preparation of gem-diacetates -Method A
To a stirred solution of aldehyde (2 mmol) and acetic anhydride (3 mmol) in dichloromethane (10 mL), GaCl 3 (17.5 mg, 5 mol%) was added, and the mixture was stirred at room temperature for the time indicated in Table 2.After reaction completion, the reaction mixture was diluted with dichloromethane and washed with saturated NaHCO 3 solution (3 x 15 mL), and then with saturated brine.The organic layer was dried over anhydrous Na 2 SO 4 and concentrated in vacuo to afford the pure corresponding gem-diacetates.General procedure for the preparation of gem-diacetates under solvent-free conditions -Method B To a stirred solution of aldehyde (2 mmol) in acetic anhydride (3 mmol), GaCl 3 (17.5 mg, 5 mol %) was added, and the mixture was stirred at room temperature for the time indicated in Table 2.After completion of reaction, the reaction mixture was extracted with dichloromethane and washed with saturated NaHCO 3 solution (3 x 15 mL), and then with saturated brine.The organic layer was dried over anhydrous Na 2 SO 4 and concentrated in vacuo to afford the pure corresponding gem-diacetates.

Table 2 .
GaCl 3 catalysed synthesis of aldehyde gem-diacetates Cl 2 , r.t., 12 min), 94% (solvent-free, r.t., 3 min) aAll the products were characterized by comparison of their spectral and physical data with those of authentic samples.b Isolated yields of corresponding gem-diacetates.e Time in hours.