Studies in the Synthesis of Bibenzyl the M.P
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Indian Journal of Chemistry Vol. 44B, August 2005, pp. 1713-1716 Note Studies in the synthesis of bibenzyl The m.p. of the synthesized stilbene was 110°C and that of bibenzyl was 52°C. In the IR spectrum, the S S Mahajan* & V A Kamath C-H stretching of the trans CH = CH unit in stilbene, C. U. Shah College of Pharmacy, S. N. D. T. Women’s was recorded at 3050 cm-1. The IR spectrum of University, Sir Vithaldas Vidyavihar, Santacruz (West), bibenzyl showed C-H stretching at 2954 cm–1. The Mumbai 400 049, India. NMR spectrum of stilbene showed peaks at δ 7.45 (s, E-mail: [email protected] 10H, Ar) and at δ 3.35 (d, J = 18, 2H, 2 × CH). The Received 24 June 2004; accepted (revised) 15 February 2005 NMR spectrum of bibenzyl showed peaks at δ 2.7 (s, 4H, 2 × CH2) and δ 6.9 (s, 10H, Ar). Synthesis of bibenzyl has been attempted using Friedel-Crafts The comparative overall percent yields of bibenzyl, reaction, Wurtz reaction, Wolff Kishner reduction using hydrazine calculated based on the starting material used, the hydrate and reductions involving Zn-NiCl2.6H2O and sodium bis- (2-methoxyethoxy)-aluminium hydride (a Vitride reagent). The reaction time and the number of steps involved in four yields of bibenzyl obtained by the four different routes have been different synthetic routes are tabulated in Table I. compared. A single-step reduction of stilbene using Zn- Scheme I shows a two-step reaction and bibenzyl NiCl2.6H2O results in the highest yield. was obtained in 62% yield. The maximum yield of bibenzyl was obtained in this scheme when Keywords: Bibenzyl, Friedel-Crafts reaction, Wurtz reaction, Wolff Kishner reduction, hydrazine hydrate, sodium the molear ratio of benzene to dibromoethane in the bis-(2-methoxyethoxy)-aluminium hydride, Vitride first step was 10 : 1 and the gravimetric ratio of reagent, 1,2-diphenylethane benzene to polyalkylates in the second step was 2 : 1. Scheme II, a single-step reaction, and Scheme III, a 7 IPC: Int.Cl. C 07 C 15/12 three-step reaction, resulted in 52 and 58% yield of bibenzyl, respectively. Scheme IV a, a single-step Bibenzyl, 1,2-diphenylethane, is an important reaction, gave the highest yield of 74.1% when structural feature of many isoquinoline alkaloids. stilbene was reduced using Zn and NiCl2.6H2O in Bibenzyl finds widespread applications in the methanol. Scheme IVb, using Vitride as a reducing synthesis of a diverse category of products like agent, gave 55% yield of bibenzyl. anthelmintic drugs1 useful against pinworms, opioid 2 Scheme IVa was found to be the most economical analgesics and also the leucotriene antagonists, and the safest route of synthesis and did not involve which act as cytoprotective agents and are useful for costly or hazardous chemicals. the prevention and treatment of ulcers3. It is an important structural component of many drugs such as Experimental Section narcotine, berberine, morphine, papaverine, laudo- nosine, corydaline and emetine2,4,5. It also finds wide Bibenzyl was synthesized using four different applicability in the manufacture of magnetic routes as shown in Figure 1. recording media, ceramic super conductor forms and Friedel-Crafts alkylation of benzene with flame retardants6,7. dibromoethane. Bibenzyl was synthesized in two Results and Discussion Table I ⎯ Comparison of four synthetic routes for bibenzyl The purity of the synthesized compounds was Scheme No. No. of Reaction time Percent yield confirmed from TLC, melting points and from IR and steps (hr) of bibenzyl NMR spectra. The melting points (m.p.) were determined in open capillaries and are uncorrected. IR I 2 8 62.0 spectra were recorded on a JASCO FT/IR-5300 II 1 14 52.0 spectrophotometer, using KBr pellet method. The III 3 6 58.0 NMR spectra were recorded on a Varian 60 MHz IV a 1 2 74.1 spectrometer. IV b 1 2 55.0 1714 INDIAN J. CHEM., SEC B, AUGUST 2005 Table II ⎯ Percent yields of bibenzyl by Friedel-Crafts alkylation Sl. Step I Step II Percent yield No. Molar ratio Gravimetric ratio of Benzene : Dibromoethane Benzene:Polyalkylates bibenzyl 1 10:1 1:1 35 2 10:1 2:1 62 3 12:1 1:1 35 4 12:1 2:1 28 C C O O Benzil 4 Wolf Kishner Reduction Scheme III Friedel-Crafts Wurtz Reaction Reaction CH2 CH2 ClH2C Scheme I Scheme II Benzene 1 Bibenzyl 2 Benzyl chloride 3 Reduction by Zn-NiCl2 6H2O Or Vitride Scheme IV (a) & (b) H C C H Trans-stilbene 6 Clemmensen's Reduction OH C C H O Benzoin 5 Figure 1 ⎯ Four synthetic routes of bibenzyl steps using Friedel-Crafts reaction (Scheme I, mixture was heated to 50–65°C for 2 hr. The reaction Figure 1). In the first step, polyalkylates were formed. mixture was diluted with water and the benzene layer Anhydrous aluminium chloride (3.33 g, 0.025 mole) containing polyalkylates was separated. It was washed was added in aliquots to a well-stirred mixture of with water, dried and benzene recovered to get 4.5 g of benzene (6.25 g, 0.078 mole) and dibromoethane polyalkylates. This step was carried out using 10:1 and (1.5 g, 0.0079 mole). The exothermic reaction was 12:1 molear ratios of benzene and dibromoethane. controlled by immersing the flask in an ice-bath during In the second step, these polyalkylates were the addition. A further portion of anhydrous aluminium converted to bibenzyl. Anhydrous aluminium chloride chloride (3.33 g, 0.025 mole) was added and the reaction (3.33 g, 0.025 mole) was added to the reaction NOTES 1715 mixture containing benzene and polyalkylates in 1:1 formed during the reaction, was extracted with ether or 2:1 gravimetric ratio, respectively. The reaction and the ether extract was dried. Ether was then mixture was heated at 80-85°C for 5 hr and processed recovered to get 58% yield of bibenzyl (Scheme III, as described in the previous step. The liquid obtained Figure 1. after the recovery of benzene was further distilled at 140°C at 8 mm of Hg. The distillate solidified in the Reduction of stilbene using Zn-NiCl2.6H2O and a form of needle shaped crystals of bibenzyl 2. Vitride reagent Synthesis of trans-stilbene by Clemmensen’s The percent yields of bibenzyl for different ratios 8 of benzene : dibromoethane in the first step and reduction . trans-Stilbene required for the synthesis benzene : polyalkylates in the second step are reported of bibenzyl in Scheme IV was synthesized in the in Table II. laboratory from benzoin 5 by Clemmensen’s reduction. A mixture of zinc dust (40.0 g, Wurtz reaction using benzyl chloride and sodium 0.612 mole), mercuric chloride (10.0 g, 0.037 mole), metal concentrated hydrochloric acid (20.0 mL) and water Small pieces of sodium, in 50% excess (5.0 g, (50.0 mL) was stirred for 5 min. The amalgamated 0.217 mole) over the theoretical quantity, were zinc thus formed was transferred to a three-necked placed in dry ether (35.0 mL). The flask was cooled flask and cooled. To this reaction flask, 95% ethanol and benzyl chloride 3 (11.00 g, 0.08 mole) was (100.0 mL) and benzoin 5 (20.0 g, 0.096 mole) were added to it slowly. After the initial vigorous added. The reaction mixture was stirred and conc. reaction was subsided, the mixture was refluxed for HCl (100.0 mL) was added to it. The temperature of 8 hr. Additional amount of sodium metal (3.0 g, the reaction mixture was maintained below 15°C, 0.13 mole) was added to the reaction mixture, in throughout the reaction. Stirring was continued for 4 portion. The reaction was found to go to completion hr. The reaction mixture was filtered. Hot alcohol after 22 hr. The reaction flask was cooled and the was added to the residue and the mixture was shaken reaction mixture was filtered to remove precipitated thoroughly to extract stilbene. The mixture was sodium chloride. The residue was washed with filtered and once again the residue was extracted ether and ether was recovered to get 38% of pure with alcohol. All the filtrates were combined and bibenzyl (Scheme II, Figure 1). cooled to get crystals of stilbene. The residue of zinc amalgam was taken in water and the traces of When all the quantity of sodium metal was added stilbene were extracted in ether. Ether layer was in the beginning of the reaction itself, the yield of 2 dried and ether recovered to get stilbene. Stilbene was found to increase from 38 to 45% and the from alcoholic extracts and ether extract was reaction time was found to reduce from 22 hr to recrystallised together from 95% ethanol to get 65% 18 hr. yield of pure stilbene 6. Stilbene thus obtained was When powdered sodium was used in place of reduced using two reducing agents. In Scheme IVa, sodium pieces, the yield of pure bibenzyl 2 was Zn-NiCl2.6H2O in methanol was used whereas in 52% and the time of reaction was found to reduce Scheme IVb, sodium bis-(2-methoxyethoxy)- to 14 hr. aluminium hydride, a Vitride reagent, was used for the reduction purpose. Huang-Minion modification of Wolff Kishner In Scheme IVa, powdered zinc (5.23 g, 0.079 mole) reduction was added to a suspension of stilbene 6 (1.06 g, In the first step, benzil 4 (2.0 g, 0.0095 mole), 0.06 mole) and NiCl2.6H2O (7.13 g, 0.03 mole) in diethylene glycol (18.62 g, 0.176 mole), hydrazine methanol (60.0 mL), in portions and with stirring.