Note Synthesis of Heneicos-6(Z)-En-11-One, Dec- 5(Z)

Indian Journal of Chemistry Vol. 49B, April 2010, pp. 495-499

Note

Synthesis of heneicos-6(Z)-en-11-one, dec- Hydroboration of dec-1-en-4-yne 4 with sodium 5(Z)-en-1-yl acetate, dec-5(Z)- en-1-yl-3- acetoxyborohydride (prepared in situ from sodium- borohydride and acetic acid in dry THF), followed by methylbutanoate (insect sex pheromones) 14 o iodination with I2/NaOH, CH3OH at O C furnished 17 Rani Jindal†, Aarti Devi, Goverdhan L Kad & 1-Iododec-4-yne 5. Grignard reagent prepared from Jasvinder Singh* 1-iododec-4-yne 5 and magnesium turnings in anhyd. Department of Chemistry & Centre of Advanced Studies in diethyl ether, on reaction with undecanal in anhydrous Chemistry, Panjab University, Chandigarh 160 014, India diethyl ether provided heneicos-6-yn-11-ol 6, which on oxidation18 with pyridinium dichromate in E-mail: [email protected] anhydrous dichloromethane furnished heneico-6-yn- Received 2 May 2008; accepted (revised) 17 December 2009 11-one 7. Compound 7 when subjected to partial hydrogenation19 in the presence of Lindlar`s catalyst Synthesis of heneicos-6(Z)-en-11-one 1, dec-5(Z)-en-1-yl in dry hexane containing a few drops of quinoline acetate 2, dec-5(Z)-en-1-yl-3-methylbutanoate 3 has been accomplished by utilizing sodium acetoxyborohydride generated under slight positive pressure of hydrogen, furnished in situ from sodium borohydride and acetic acid as the key step 1 (Scheme I) for selective hydroboration-iodination/oxidation. Hydroboration of dec-1-en-5-yne 8 with sodium acetoxyborohydride (prepared in situ from sodium Keywords: Selective, hydroboration, oxidation, acetoxyborohydride and acetic acid in dry THF), followed by borohydride, pheromones oxidation with alkaline hydrogen peroxide furnished dec-5-yn-1-ol 9, which on partial catalytic hydro- Heneicos-6(Z)-en-11-one 1, is a pheromone of the 19 Douglas Fir Tussock moth, Orgyia pseudotsugata a genation over Lindlar’s catalyst in dry hexane yielded the dec-5(Z)-en-1-ol 10 quantitatively. severe defoliator of firs in Western North America. 20 Smith et al.1 were the first to isolate this compound. Acetylation of 10 with acetic anhydride and pyridine 2 furnished 2 in 65% yield. Esterification of 3-methyl- Dec-5(Z)-en-1-yl acetate 2, has been isolated from 13 the EAG active glands of turnip moth Agrotis segetum butanoyl chloride with dec-5(Z)-en-1-ol and (Noctuidae Lepidoptera), is the active sex pheromone pyridine in dry DCM furnished dec-5(Z)-en-1-yl 3- component of Coleophora vaccinella3, Euxoa methylbutanoate 3 in 85% yield nigricans4, Haplodrine superstes and Emmetis trabealis. This pheromone has been proved to have a Experimental Section luring effect for turnip moth up to attractant loading 1H NMR spectra were recorded on Varian EM- of 10-6μg. Dec-5(Z) -en-1-yl-3-methylbutanoate 3 is 360(60-MHz) spectrometer and the Chemical Shifts another insect sex pheromone isolated from the are expressed as δ values downfield from TMS, which female pine emperor moth Naudaurelia cytherea is used as internal standard and IR spectra were fabr5, a serious pest in pine plantations of South recorded as liquid films on a Perkin-Elmer Model -1 Africa. Henderson et al. have isolated and identified RXI FT-IR spectrophotometer (νmax cm ) The glass it, via comparison of its IR and NMR data with its apparatus and syringes were dried at 140°C for 4 hr 6-13 synthetic analogue. Literature reports a number of and assembled under nitrogen. THF was distilled over synthesis of these compounds. sodium benzophenone just prior to use. During work In continuation of our work on selective hydro- ups all organic solvents with density less than water boration-oxidation studies with sodium acetoxy- were dried over anhyd. Na2SO4 and those with density 14-16 borohydride , we herein report simple and elegent more than water with CaCl2. synthesis of heneicos- 6(Z)-en-11-one 1, dec-5(Z)- en-1-yl acetate 2, dec-5(Z)-en-1-yl 3-methylbuta- 1-Iododec-4-yne 5 noate 3. A dry 100 mL flask equipped with stirring bar, septum in let and reflux condenser was flushed with ―――――― † nitrogen. The flask was charged under nitrogen, with Present address: SVCP, Ramnagar Banur, Distt Patiala, India

496 INDIAN J. CHEM., SEC B, APRIL 2010

NaBH4,CH3COOH THF, O0C I

I2,NaOH, CH3OH 4 5

OH CH3(CH2)8CH2CHO

Mg, THF 6

PDC, CH2Cl2

O0C 7

H2, Lindlar's catalyst

Hexane 1

Scheme I

CH3COOH, NaBH4,THF OH

H2O2/NaOH 9 8

H2 Lindlar's catalyst

OH OAc Ac2O Pyridine 10 2

(CH3)2CHCH2COCl Pyridine, CH2Cl2

3 O

Scheme II

sodium borohydride (0.756 g, 20 mmoles) followed by dropwise addition of 10 mL of 3 M solution of by addition of dry THF (40 mL) via syringe. The flask sodium hydroxide in methanol. After stirring for 10 was immersed in an ice-bath and to it was added min at RT the reaction-mixture was poured into cold glacial acetic acid (1.2 g, 20 mmoles) slowly under water (50 mL) containing 1 g of sodium thiosulphate the blanket of nitrogen. The contents were allowed to to remove excess iodine. The aqueous layer was stir and then dec-1-en-4-yne (4, 2.72 g, 20 mmoles) extracted with ether (3 × 20 mL). The combined THF- was added to it slowly via syringe. The contents were ether layer was dried, solvent evaporated and the stirred for 16 hr at RT for complete hydroboration.To product purified by column chromatography over the solution of organoborane prepared as above, was silica gel (2% ethyl acetate in n-hexane) to give 5 added iodine (6.35 g, 25 mmoles) all at once followed (3.3g, 63%, Scheme II).

NOTES 497

IR(neat): 2910, 2880, 2260, 1460, 610 cm-1; the presence of Lindlar’s catalyst (0.0001 g) and 1 H NMR (CCl4, 60MHz): δ 0.9(t, J = 5Hz, 3H, quinoline (1 drop) in dry hexane. When one -CH2CH3), 1.1-1.3 (m, 8H, saturated methylene equivalent of hydrogen was taken up, the catalyst was protons), 2.2 (m, 4H, -CH2CH2C≡CCH2CH2-), 3.2 (t, filtered off. Organic phase was washed with dilute J = 7 Hz, 2H, -CH2CH2I). acetic acid, water and dried. The solvent was removed and the residue was chromatographed over silica gel Heneicos-6-yn-11-ol 6 to furnish the required ketone 1 (0.08 g, 80%).

A flame dried, nitrogen gas flushed 100 mL three IR(neat): 3010, 2900, 2840, 1740, 1640, 1450, -1 1 necked round-bottomed flask, fitted with a condenser 710 cm ; H NMR (CCl4, 60 MHz): δ 0.9 (t, J = 5Hz, and an addition funnel, was charged with magnesium 6H, 2 × -CH2CH3), 1.1-1.2 (bs, 24H, saturated methy- turnings (0.05 g, 2.08 mmoles), dry ether (5 mL) and a lene protons), 2.0-2.3 (m, 8H, -CH2CH2CH = small crystal of iodine. To the resulting mixture was CHCH2CH2-, -CH2CH2COCH2CH2-), 5.4-5.5(m, 2H, added, a few drops of 1-iododec-4-yne (5, 0.5 g, 1.8 -CH2CH=CHCH2-). mmole). The flask was warmed over a heating pouch to initiate the reaction, following which the remaining Dec-1-en-5-yne 8 iodide was added over a period of 1 hr. When all the To ethyl magnesium bromide in 100 mL round magnesium turnings had reacted, the reaction-mixture bottomed flask [prepared from ethyl bromide (6.6 g, was cooled to 0ºC. To it was added drop-wise, a solution 61 mmoles) and Mg turning (1.54 g, 61 mmoles)] was of undecanal (0.321 g, 1.89 mmole) in dry diethyl ether added slowly, a solution of 1-hexyne (4.4 g, 54 (25 mL) over a period of 1 hr. The reaction was allowed mmoles) in dry THF under an atmosphere of nitrogen. to stir overnight, quenched with saturated ammonium After the addition, the reaction-mixture was warmed chloride solution and the organic layer was washed with in water-bath (55ºC) for 40 min. The solution was water (2 × 15mL) brine and dried. The solvent was then cooled to RT and CuCl (0.24 g, 2.42 mmoles, evaporated in vacuo and the crude product purified over prepared freshly) was added. After 20 min a solution a silica gel column using 10% ethyl acetate in n-hexane of 4-bromo-1-butene (7.4 g, 55 mmoles) in dry THF as an eluant to provide 6 (0.418 g, 82.5%). was added gradually via syringe and the contents IR(neat): 3400, 2910, 2210, 1345 cm-1; 1H NMR were stirred at RT for 12 hr. The reaction- mixture was warmed on water bath at 55ºC for 2 hr. After (CCl4, 60 MHz): δ 0.9 (t, J = 5 Hz, 6H, 2×-CH2CH3), 1.1-1.5 (m, 28H, saturated methylene protons), 1.7- cooling to RT the reaction-mixture was treated with 2.0 (m, 4H, -CH CH C≡CCH CH -), 3.6-3.8 (m, 1H, - aq. solution in separatory funnel, the upper layer was 2 2 2 2 separated and aqueous layer was extracted with ether CH2CH(OH)CH2-), 4.6-4.7 (bs, 1H, -OH, exchangeable with D O). (2 × 20 mL). The combined organic layer was washed 2 with water and dried. Evaporation of solvent, Heneicos-6-yn-11-one 7 followed by column chromatography over silica gel To a mixture of pyridinium dichromate (1.29 g, using 5% ethyl acetate in n-hexane as the eluant, 3 mmoles) in dry DCM (10 mL) taken in 100 mL furnished 8 (4.9 g, 67%). round bottomed flask was added heneicos-6-yn-11-ol IR(neat): 3010, 2940, 2880, 2260, 1640, 1450, 840 -1 1 (6, 0.4 g, 1.3 mmole) in dry dichloromethane (25 mL) cm ; H NMR (CCl4, 60 MHz): δ 0.9 (t, J = 5Hz, 3H, at 0°C. Stirring was continued for 8 hr and the -CH2CH3), 1.1-1.5 (m, 4H, saturated methylene reaction-mixture was passed through a short active protons), 1.9-2.5 (m, 4H, -CH2CH2C≡CCH2CH2-), alumina (2 g) column. Solvent was evaporated in 2.7-2.9 (m, 2H, CH2=CHCH2CH2-), 4.8-5.3 (m, 2H, - vacuo to furnish 7 (0.206 g, 52%). CH=CH2), 5.4-6.2 (m, 1H, -CH2CH=CH2). IR(neat): 2910, 2180, 1700, 1410 cm-1; 1H NMR Dec-5-yn-1-ol 9 (CCl4, 60MHz): δ 0.9 (t, J = 5Hz, 6H, 2 × -CH2CH3), 1.1-1.4 (m, 24H, saturated methylene protons), 1.7- A dry 100 mL flask equipped with magnetic 1.9 (m, 4H, -CH CH C≡CCH CH -), 2.2 (t, J=5Hz, stirring bar septum inlet and reflux condenser, was 2 2 2 2 flushed with nitrogen. The flask was charged under 4H, -CH2CH2COCH2CH2-). nitrogen with sodium borohydride (0.74 g, 20 Heneicos-5(Z)-en-11-one 1 mmoles) followed by addition of dry THF (40 mL) Heneicos-6-yn-11-one (7, 0.1 g, 0.33 mmole) was via syringe. The flask was immersed in an ice bath hydrogenated under positive pressure of hydrogen in and glacial acetic acid (1.2 g, 20 mmoles) was added

498 INDIAN J. CHEM., SEC B, APRIL 2010

to it slowly under the blanket of nitrogen. The The organic layer was washed successively with 5% contents were allowed to stir and then dec-1-en-5-yne HCl, water, 5% NaHCO3 (2 × 5 mL) solution, brine (8, 2.72 g, 20 mmoles) was added to it slowly via and dried. Evaporation of solvent followed by syringe and further stirred for 16 hr at RT for purification over silica gel column chromatography complete hydroboration. using 2% ethyl acetate in n-hexane as the eluant The organoborane thus prepared in dry THF was furnished 2 (0.175 g, 65%). cooled to 0ºC and to it was added aqueous NaOH IR(neat): 3010, 2940, 1720, 1650, 1460 cm-1; 1 (3 M, 8 mL) and 30% H2O2 (8 mL) dropwise. The H NMR (CCl4, 60MHz): δ 0.9 (t, J = 5Hz, 3H, temperature was then raised slowly and the reaction- -CH2CH3), 1.3-1.7 m, 8H, saturated methylene protons), mixture was then heated at 70ºC for 1 hr. The 2.1 (s, 3H, -OCOCH3), 2.2-2.3 (m, 4H, -CH2CH2CH = contents were cooled and isolation of the product was CHCH2CH2-), 4.1 (t, J = 5Hz, 2H, -CH2CH2OCOCH3), accompanied by pouring the cooled two phase 5.3-5.7 (m, 2H, -CH2CH=CHCH2-). reaction-mixture into a separatory funnel, followed by extracting with diethyl ether (3 × 20 mL). The Dec-5(Z)-en-1-yl 3-methylbutanoate 3 combined THF-diethyl ether extract was washed with A solution of dec-5(Z)-en-1-ol (10, 0.25 g, water, brine and dried. Evaporation of the organic 1.6 mmole), 3-methylbutanoyl chloride (0.241 g, layer under vacuum gave crude product which was 2 mmoles) and 1.75 mL of pyridine in 15 mL of purified using silica gel column chromatography (5% methylene chloride was stirred at RT for 18 hr. It was ethyl acetate in n-hexane) to furnish 9 (1.9 g, 62%). then washed 2 N HCl, 4% NaOH, saturated brine -1 IR (neat): 3400, 2910, 2240, 1340, 1210 cm ; solution and dried (Na2SO4). Evaporation of solvent 1 H NMR (CCl4, 60 MHz): δ 0.9 (t, J=5Hz, 3H, and subsequent purification via silica gel column -CH2CH3), 1.2-1.8 (m, 8H, saturated methylene chromatography using 5% ethyl acetate in n-hexane protons), 1.9-2.1 (m, 4H, -CH2CH2C≡CCH2CH2-), 3.5 as elutant furnished 3 (0.32 g, 87%). -1 (t, J = 4Hz, 2H, -CH2CH2OH), 3.9 (bs, 1H, IR(neat): 3010, 2910, 2890, 1750, 1640 cm ; 1 -CH2OH, D2O exchangeable). H NMR (CCl4, 60MHz): δ 0.9 (d, J = 6Hz, 6H, -CH(CH3)2), 1.0 (t, J=5Hz, 3H, -CH2CH3), 1.2-1.7 Dec-5(Z)-en-1-ol 10 (m, 8H, saturated methylene protons), 1.8-2.0 (m, 1H, Dec-5-yn-1-ol (9, 2 g, 13 mmoles) was subjected to -CH2CH(CH3)2), 2.1-2.5 (m,6H,-COCH2CH-, partial catalytic hydrogenation under positive pressure -CH2CH2CH = CHCH2CH2-), 3.9 (t, J = 6Hz, 2H, of hydrogen over Lindlar’s catalyst (0.005 g), -OCH2CH2-), 5.3-5.5 (m, 2H, -CH2CH=CHCH2-). poisoned with quinoline (1 drop) in dry n-hexane (10 mL). When one equivalent of hydrogen was taken Acknowledgement up, catalyst was filtered off. The solution was washed with dil. acetic acid, water and dried. The solvent was Authors are thankful to UGC, New Delhi for evaporated and the residue chromatographed over providing financial assistance. silica gel using 5% ethyl acetate in n-hexane as the eluant to furnish 10 (1.41 g, 70%). References IR(neat): 3500, 3010, 2950, 2880, 1620, 1440, 725 1 Smith R G, Daterman G L & Daves G D, Jr Science, 188, cm-1; 1H NMR (CCl , 60 MHz): δ 0.9 (t, J = 5Hz, 3H, 1975, 63. 4 2 Bestmann H J, Vostrowsky O, Koschatzhy K, Platz H, Brosck -CH2CH3), 1.3-1.8 (m, 8H, saturated methylene T, Kantardjiew I, Rhienwald M & Knawl W, Angew Chem Int protons), 2.1-2.3 (m, 4H, -CH2CH2CH=CHCH2CH2-), Ed, 17, 1978, 768. 3.7 (t,, J = 4Hz, 2H, -CH2CH2OH), 3.9 (bs, 1H, -OH, 3 Willemse L P M, Booij C J H & Voermann S L, Angew Entomol, 103, 1987, 508. D2O exchangeable), 5.2-5.7 (m, 2H, -CH2CH = CHCH ). 4 Szocs G, Toth M & Novak L Z, Angew Entomol, 96, 1983, 2 56. 5 Henderson H E, Warren F L, Augustyn O P H, Burger B V, Dec-5(Z)-en-1-yl-acetate 2 Schnider D F, Boschoff P R, Spies H S C & Geetsems H, J To an ice cooled mixture of dec-5(Z)-en-1-ol (10, Chem Soc Chem Commun, 1972, 686. 0.212 g, 1.4 mmole) and pyridine (0.345 g, 7 mmoles) 6 (a) Smith R G & Daves G D, J Org Chem, 40, 1975, 1593; (b) Kocienski P J & Cernigliaro G J, J Org Chem, 1976, 2927; was added acetic anhydride (0.2g, 2 mmoles) slowly (c) Fentizon M & Lazare C, J Chem Soc Perkin Trans 1, and stirred at RT for 3 hr. The reaction-mixture was 1978, 842. quenched with ice and extracted with ethyl acetate. 7 Akermark B & Lyungyvist A, J Org Chem, 43, 1978, 4387.

NOTES 499

8 Sharma M L, Verma S & Chand T, Indian J Chem, 34B, 13 Wenkert E, Ferrena V F, Michelotti E L & Tingoli M, J Org 2002, 1030. Chem, 50, 1985, 719. 9 White J & Whiteley C G, Synthesis, 1993, 1141. 14 Singh J, Sharma M, Kad G L & Kaur J, Indian J Chem, 46B, 10 Hayes J F, Shipman M & Twin H, J Org Chem, 67, 2002, 2007, 2053. 935. 15 Gautam V K, Singh J & Dhillon R S, J Org Chem, 53, 1988, 11 Trehan I R, Singh J, Arora A K, Kaur J & Kad G L, Indian J 187. Chem, 33B, 1994, 468. 16 Dhillon R S, Nayyar K & Singh J, Tetrahedron Lett, 33, 1992, 12 (a) Konolew B G, Dzhumakulov T & Abduvakhabov A, Khim 6015. Prir Soedin, 1986, 122; (b) Aurelia B A, Barabas A, Oprean 17 Caheiz G, Alexakis A & Normant J F, Tetrahedron Lett, 33, I, Csonka H, Julianna & Honosan F, Rav Roum Chim, 28, 1978, 3013. 1983, 741; (c) Odinokov V N, Balezina G G, Ishmuratov G, 18 Cornforth R H, Cornforth J W & Popjak G, Tetrahedron, 18, Yu Vakhitov R S H & Tolstikov G A, Khim Prir Soedin, 3, 1962, 1351. 1985, 395; (d) Odinokov V N, Galeeva R I, Sokol’s Kaya O 19 (a) Lindlar H, Helv Chim Acta, 55, 1952, 446; (b) Wadsworth V, Dzhemileva G A & Tolstikov G A, Dok Aka Nauk SSR, W S & Emmons W D, J Am Chem Soc, 83, 1961, 1733. 280, 1985, 646; (e) Yu Q T, Liu B N, Zang J Y & Haung Z H, 20 Yadav J S, Upender V, Sekhran T & Reddy R E, Indian J Lipids, 23, 1988, 804. Chem, 27B, 1988, 1012.