Reactions of Chlorine Gas on Benzaldehyde-din-alkyl Acetals

Reactions of chlorine gas on six aromatic acetals, the benzaldehyde di-n-alkyl acetals, C6H4-CH(OR)2 where R=ethyl (1a), n-propyl (2a), n-butyl (3a), isobutyl (4a), n-amyl (5a) and isoamyl (6a) were studied. The products were analyzed by IR and H NMR spectroscopic techniques and were found to be ring chlorinated alkyl benzoates. A plausible mechanism has been proposed based on the experimental observations and the effect of the alkyl groups on the product yield.


Introduction
Acetals play a vital role in bioorganic research in exploring anti-malarial 1 , anti-viral 2 , anti-bacterial 3 , anti-tumor 4 , and anti-cancer activities.The studies of enzymes 5 , thrombin inhibitors 6 , ADP-ribose linkages to proteins 7 , bioprosthetic devices 8 , and knee replacement 9 have been made through the investigation of acetals.The acetal research has contributed much towards the synthesis of catalytic antibodies, oligonucleotide and hypolipidemic agents.Acetal derivatives of aldehydes are valuable in synthesis either as intermediates or as protecting groups 10,11 , It is known that acetals are susceptible to addition 12 , oxidation 13 , reduction 14,15 , rearrangement 16 , condensation 17 and hydrolysis 18 in presence of catalysts.The literature contains a few references on the preparations 19,20 , and reactions 21,22 of aromatic and heteroaromatic acetals resulting in synthetically important compounds as major products 23,24 .But the literature lacks detailed study on the action of halogens on aromatic acetals.Action of Lewis acids on acetals in homogeneous and heterogeneous media have been investigated by various researchers and in most of the cases synthetically important compounds such as alkoxy alcohols, ethers and esters have been obtained. 16,25The requirement of steric relief from crowding of the groups around the methine (benzal) carbon atom in the acetal is expected to be the driving force for the ethereal oxygen atom to coordinate with an acceptor synthon, which may result in the cleavage of the alkoxy group leaving the methine sp 3 carbon atom to become a roomier sp 2 carbon atom.The Lewis acids have quenched such a thirst of the ethereal oxygen.The effect has been studied and the products have been analyzed by researchers.
In the place of Lewis acids the reagent selected in the present investigation is Cl 2 , which can quench the thirst of the ethereal oxygen atom by accepting its lone pair.Thus the present study aims on the action of Cl 2 on some aromatic acetals derived from benzaldehyde and alcohols of different alkyl group size and is a new venture.The following benzldehyde dialkyl acetals have been synthesized and taken for study in CCl 4 medium.

Experimental
Benzaldehyde and the alcohols were procured from SDS fine chemicals, Mumbai and were distilled before use.IR spectra were recorded in Perkin Elmer 1800 FT IR spectrophotometer and the 1 H NMR spectra on a DRX-300 spectrometer (300 MHz) using TMS as internal standard.

Preparation of 2a
This acetal was synthesized using p-toluene sulphonic acid as the catalyst 27 .The aldehyde was refluxed for 8 hours with the alcohol in benzene containing a little p-toluene sulphonic acid.The equilibrium was driven toward the product by collection of the water formed using a Dean-Stark trap.When no more water was collected, the benzene solution was cooled, washed with 1M sodium bicarbonate solution and then with water.The solution was dried over potassium carbonate.After evaporation of the solvent, the liquid was distilled under reduced pressure.IR (ν max , cm -1 ) : 1040-1050 1 H NMR (δ, ppm) : 0.9 (6H, t, 2×CH Preparation of 3a-6a 28 Molecular proportions of the aldehyde and alcohol containing 7% by weight of anhydrous calcium chloride in pure dry benzene were refluxed in an apparatus equipped with a Dean-Stark trap carrying a reflux condenser until no more water was collected.The benzene added was to facilitate water separation.The acetals were preserved over potassium carbonate and distilled prior to use.

Preparation of chlorine gas
Concentrated hydrochloric acid was added in drops on potassium permanganate crystals and the chlorine gas evolved was allowed to pass through concentrated sulphuric acid solution, got dried and used for the reactions.

Results and Discussion
Action of chlorine on acetals 0.2 mol of acetal in 50mL of purified CCl 4 was taken in a 250mL three-necked round bottomed flask, fitted with a delivery tube to pass the dry chlorine gas, a mercury thermometer sealed stirrer and a calcium chloride guard tube.The flasks were cooled in an ice bath.To the well-stirred acetal solution kept at 0 °C, pure dry chlorine gas was passed for 15 minutes.Stirring was continued for another half an hour.The reactions were stopped and 25mL of 10% sodium hydroxide solution was added to remove the excess chlorine gas as water-soluble sodium chloride and sodium hypochlorite.The aqueous layer was discarded and the organic layer was dried over anhydrous sodium sulphate and the solvent was distilled off.After isolating the individual compounds by column chromatography and thin layer chromatography, each one of the products was tested for the presence of chlorine in the nucleus as well as in the side chain.They were characterized by IR and PMR spectra (Table 1).Further they were quantitatively analyzed by GLC, with authentic samples co injected as references.The products were characterized and identified to be the ring chlorinated esters.The formations of esters during the action of chlorine on acetals indicate that the reactions involve E 2 mechanism followed by ring halogenation (Scheme 1)

Cl
Step 1 Step 2 E 2 Step 3 Chloro oxonium ion complex π Step 5 Step 4 σ E 2 complex Scheme 1. Mechanism of ring chlorination of acetals by the action of chlorine Such a ring substitution has been reported in the nitration reaction 29 of methyl phenethyl ether using dinitrogen pentoxide, ring chlorination of anisole by hypochlorous acid 30 , migration of halogen in the Orton rearrangement. 31The formation of ring halogenated ester from acetals by as explained by the E 2 mechanism (Scheme 1) is also very similar to those reported in the work of Xavier and Arulraj. 16In their study the ester formation had occurred in a concerted way with the removal of the benzal proton with the concomitant cleavage of the σ bond of the alkyl group.

Effect of alkyl group on the product yield
Studies on the effect of alkyl group in the halogenated ester formation is shown in  2 shows low percentage of products as the size of the alkyl group increases.It is self evident that the chlorine-oxygen intermolecular bond would be sensitive to steric effect caused by the alkoxy groups because branching of alkyl group would prevent chlorine from close approach 32 .

Table 1 .
Spectra characterizations of ring chlorinated esters

Table 2 Table 2 .
Percentage distribution of ring chlorinated ester products of acetals by the action of chlorine