Indi an Journal of Chemi stry Vol. 408, May 200 I. pp. 386-390

Ultrasound mediated synthesis of a few naturally occurring compounds

Jasvinder Singh*, Jasamrit Kaur, Sandeep Nayyar, Monica Bhandari & Goverdhan L Kacl

Department of Chemistry. Pan jab University. Chandigarh-1600 14, India

Received 14 Februwy 2000: accepted (revised) 5 June 2000

Synthesis of 2-methylheptadecane 1, I 4-methylpentadecan-3-one 2, 6-oxo- I -nonanol 3, 5-(Z)-undecenoic acid 4 and 2-tridecanone 5 have been accompli shed utili zing zi nc-copper couple catalyzed conjugate addition of a.~-unsaturated carbonyl compounds under aqueous sonochemical conditions as the key step.

2-Methy lheptadecane 1 is the active sex pheromone1

component of the tiger moth and different species of the Artiidae family (Holo111elina laeta, H. aurantiaca and Pyrrharctia isabe/la) . I4-Methylpentadecan-3-one 2 is one of the plant part compositions2 of Partheniu111 hysteroplwrous Linn (compositae).6-0xo-l-nonanol 3 is the rectal gland secretion3 of mature male flies belonging to Dacus species (Bactrocera carambolae, B. wnbrosa and B. halfordiae).5-(Z)-Undecenoic acid 4 is the sex pheromone component4 of the varied carpet beetle Anthrenus verbasci L. 2-Tridecanone 5 is the major aggregation pheromone5 component of mature males of Drosophila hydei (Diptera, Drosophilidae) and is also found in a number of animal and plant secretions. Literature reports a number of syntheses of these compounds6.

The use of ultrasounic waves to carry out chemical reactions is well documented7 and as reported by Luche eta!} ultasound is beneficial for enhancing the rate of a reaction particularily those involving free radical intermediates, thus accelerating the reaction. Sonication allows the usc of non-activated and crude reagents as well as an aqueous solvent system, therefore it is ecofriendly and non-toxic. In continuation with our earlier work9 utilizing ultrasonic energy in the synthesis of natural products, compounds 1 to 5 have been synthesized employing aqueous sonochemical conditions in conjunction with zinc-copper couple to bring about the add ition of alkyl halide to a,~-unsaturated carbonyl compounds (Schemes I to V).

Pyridinium dichromate oxidation 10 of l-tridecen-3-ol1 1 6 furnished 1-tridecen-3-one 7 which on treatment with 1-iodo-3-methylbutane 8 in the presence of Zn(Cu) couple under aqueous ultrasonic conditions8 provided 2-methy lheptadecan-7 -one 9. Compound 9 when subjected to Wolff-Kishner

reduction 12 with potassium hydroxide and hydrazine hydrate afforded 1 in 72% yield (Scheme 1).

Protection 13 of 6-bromo-1-hexanol 10 to 6-bromo-1-tetrahydropyranyloxy hexane 11 with 3,4-dihydro-2H-pyran, followed by dilithium tetrach lorocuperate catalyzed coupling 14 with isopentylmagnesium iodide in anhyd. THF gave 9-methyl-1-tetrahydropyranyloxy decane 12, which on treatment with triphenylphosphine and carbon tetrabromide 15

afforded 9-methyl-1-bromodecane 13 and subsequent reaction under sonochemical conditions with 1-penten-3-one in the presence of Zn(Cu) couple provided compound 2 (Scheme II).

Conjugate addition of 3-bromo-1-propanol 14 to 1-hexen-3-one1 6 15 in the presence of Zn(Cu) couple on sonication8 in ethanoi-H20(9: 1) solvent system yielded 6-oxo-1-nonanol 3 (Scheme III).

Iodination 17 of 2-(Z)-octen-1-ol 18 16 with sodium iodide and boron trifluoride etherate in acetonitrile gave 1-iodo-2-(Z)-octene 17 which on exposure to sonication8 in the presence of methyl 2-propenoate provided 5-(Z)-undecenoate 18 and subsequent hydrolysis using KOH in ethanol 19 afforded 5-(Z)­undecenoic acid 4 (Scheme IV).

Zinc-copper couple induced addition8 of 1-iodononane 19 to 3-buten-2-one 20 in an ethanol­water (9: 1) system on ultra onic irradiation afforded 2-tridecanone 5 (Scheme V).

Experimental Section 1H NMR spectra were recorded on Varian EM -360

(60 MHz) spectrometer and the chemical shifts are expressed as 8 (ppm) values downfield from TMS which is used as the internal standard and IR spectra as liquid films on a Perkin-Elmer infrared 1430 spectrophotometer (Vmax in cm-1). The ultrasonic source used for the reactions was the 'Heat System'

SINGH et al.: ULTRASOUND MEDIATED SYNTHESIS OF A FEW NATURALLY OCCURRING COM POUNDS 387

OH i -

6

ii -)))))

7

iii -

Reagents: i)PDC, CH2CI2, ooc (ii)(CH3)2 CHCH2CH2I (8), Zn(Cu) , EtOH: H2

0(9:1) (iii)NH2NH2 (99%), KOH , HOCH2CH20H.

Scheme I

Br

HO......_ ~ ../"-... .........._ i ......., ......., ...........- ' Br -

10

ii -13

iv -)))))

Q/o~Br 0

11

2

iii -

Reagents: i) DHP, CH2CI2, H+ (ii) 8, Mg, Li2 CuCI4, anhyd . THF, -10°C (iii) CBr4, PPh3 , CH2CI2

(iv) CH3CH2COCH=CH2, Zn(Cu) , Et0H-H20(9:1 ).

Scheme II

Probe Sonicator. Modei-XL 20 15 (20kHz). 1-Tridecen-3-one 7. To a sti rred suspension of

pyridinium dichromate (23.02g . 61.22 mmoles) in dry methylene chl oride (75 mL) was added 1-tridecen-3-ol 6 (6.00g,30.6 l mmoles) at 0°C. Stirring was continued fo r 9hr and then the reaction mi xture was passed through an alumina (ac ti ve, 30g) column fo llowed by evapora ti on of the solvent whi ch provided compound 7 in 64. 1% yield (3.84g); 1 H

MR (CCl4): 1.00 (t, 1=6Hz, 3H, -CH2CH3), 1.10-1.40 (m. l6H, methy lene protons), 2.55 (t, 1=6Hz,2H, -COCH2CH2- ), 5.60-5 .90 (del, 1=4,5 Hz, 1 H, CH 2=CHCO-), 6. 10-6.40 (m, 2H, CH2=CH-); lR (CC14): 1700, 1660, 1420, 12 10.

2-Mcthylheptadecan-7 -one 9. A mixture of

ethanol-water (9: I, 12 mL), zinc dust (0.53g, 8.2 1 mmoles) and copper (I) iod ide (0.48g,2.54 mmoles) at 0°C taken in a 30mL ultrasonic vessel was son icated for 5 min. To the resultant black suspension under sonication was added l-iodo-3-methylbutane 8 ( 1.07 g,5.39 mmoles) in ethanol (2 mL) dropwise, fo ll owed by add ition of l-tridecen-3-one 7 (0.70g, 3.57mmoles) in ethanol (2mL). After sonication fo r 30 min , the reaction mi xture was quenched wi th brine, solvent evaporated in vacuo and taken up in diethyl ether (30 mL), washed with water (2 x 5 mL), brine and dried. Removal of solvent under vacuum followed by silica gel column chromatography (10 % ethyl acetate in hexane) afforded compound 9 (0.58g, 60.42 %); 1H NMR (CC14 ): 0.90 (d , J=6Hz, 6H. -CH

388 INDIAN J CHEM ., SEC B, MAY 2001

Br~OH

14 +

-)))))

0

~ 15

0

~OH 3

Reagents: i)Zn(Cu),EtOH:Hp(9:1 ).

Scheme III

16

~ )))))

~I 19

___i__. )))))

+

5

0

~ 20

Reagents: i)Zn(Cu),Et0H:H20(9:1 ).

Scheme V

17

Reagents: i)Nal,BFpEt2,CH

3CN (ii)CH

2 =CHCOOCH

3,Zn(Cu),EtOH:H

20(9:1)

(iii)KOH,EtOH . ~.

Scheme IV

(CH3) 2) , 1.00 -1 .70 (m, 251-l, methylene and methyl protons), 2.10-2.50 (m, 51-l, -CH(CH3)2, -CH2CH2-COCH2CI-Ir ); IR (CCI.1): 2990-2870,1720, 1370.

2-Methylheptadecane 1. A mixture of compound 9 (0.500g, 1.87 mmoles), potassium hydroxide (0.353g, 6.30 mmoles) and hydrazine hydrate (99%, 0.25 mL) in ethylene glycol (2.5 mL) was refluxed 12, in a Dean and Stark water separator for 6hr. On usual work-up and column chromatography (hexane) it furnished compound 1 (0.342g, 72%); 11-l NMR (CC14 ): 0.90 (d, 1=6 Hz, 6H, -CH(CH3)z), 1.00 -1.90 (m, 31 1-I, methylene and methyl protons), 2.00-2.50 (m, I I-I -CH(CH3)z); IR (CCI4): 3000-2920, 1370 (Fou nd : C,63.45; H,36.51.C18H38 requires C,63 .78; H,36.22%).

6-Bromo-1-tetrahydropyranyloxy hexane 11. 6 .. Bromo-1-hexanol 10 (lOg, 55.25 mmoles) was protected 13 to afford compound 11 in 66% yield (9.66g) using 2,3-dihydro-2H-pyran (4.64g,55.25 mmoles) in dry methylene chloride(60 mL) ; 1H NMR (CCI4): 1.50-2.10 (m, 141-l, saturated methylene protons), 3.30 -3.90 (m, 61-I, BrCH2CH2-, -Cl-l2CH20-, -OCH2Cl-lr) , 4.95 (t, 1=41-Iz, 1 1-I, -OCHO-); fR(neat) : 2970, 1210, 1120, 890, 810.

9-Methyl-1-tetrahydropyranyloxydecane 12. 1-Iodo-3-methylbutane 8 (5.16g, 26.04 mmoles) in anhyd. THF (25 mL) was added to a round-bottomed flask charged with magnesium turnings (0.62g, 26.04 mmoles), anhyd. THF (5mL) and a small crystal of iodine. When all of the magnesium turnings had reacted, compound 11 (6.90g, 26.04 mmoles) was added drop wise at -10°C, followed by the addition 14

of 0.1 M Li2CuC14 in anhyd. THF (2 mL) and the reaction mixture was stirred overnight. On usual work-up and purification by silica gel column chromatography (2% ethyl acetate in hexane) it gave compound 12 in 39.2% yield(2.61g) ; 11-l NMR (CCl4) : 1.00 (d, 1=61-lz, 61-I, -CH(CH3h), 1.50-2.00 (m, 201-I, saturated methylene protons), 2.00-2.40 (m, lH , -CH(CH3)z), 3.40-3.90 (m, 4H, -OCH2CH2- ,

-CH2CH20-), 4.90 (t, 1=4 Hz, I H, -OCHO- ); IR(neat):2890, 1375,1210, 1120.

9-Methyl-1-bromodecane 13. Compound 12 (1.50g, 5.86mmoles) in dry methylene chloride (20 mL) was treated 15 with dry carbon tetrabromide (2.72g, 8.2 mmoles) under nitrogen atmosphere and cooled to 0°C. To the reaction mix ture was added triphenylphosphine (4.30g, 16.41 mrnoles) and stin·ed overnight. Purification of the resultant mixture

SINGH era/.: ULTRASOUND MEDIATED SYNTHESIS OF A FEW NATURALLY OCCURRING COMPOUNDS 389

through a short silica column afforded pure 13 ( 1.0 I g, 73.2%); 1H NMR (CCl4): 0.90 (d, 1=6Hz, 6H, -CH­(CH3h); 1.50-1.90 (m, 14H, saturated methylene protons), 2.00-2.40 (m, 1 H -CH(CH3)2), 3.45 (t, 1=6Hz, 2H, BrCH2CHr);IR( neat): 2970-2920, 1410, 1375.

14-Methylpentadecan-3-one 2. A mixture of ethanol-water (9 : 1,12 mL), zinc dust (0.22g, 3.38 mmoles), Cui (0.20g, 1.05 mmoles), 1-penten-3-one (0.12g, 1.46 mmoles) in ethanol (2 mL) and 9-methyl-1-bromodecane 13 (5.16g, 26.04 mmoles) in ethanol (2 mL) at 0°C taken in a 30mL ultrasonic vessel was sonicated for 35 min. Usual work-up followed by silica gel column chromatography (8% ethyl acetate in hexane) furnished compound 2 (0.21g, 59.93%); 1H NMR (CCl4): 0.90 (d, 1=6Hz, 6H, -CH(CH3)2), 1.15 (t, 1=6Hz, 3H, CH3CH2CO-), 1.50-1.80 (m, 18H, saturated methylene protons), 2.00-2.50 (m, 5H, CH3CH2COCH2CHr, -CH(CH3h); IR(CCl4): 3080, 2975, 1750, 1375 , 740, 720 (Found : C,80.25; H,13.03. C16H320 requires C, 80.00; H,13.30%).

6-0xo-1-nonanol 3. A mixture of ethanol-water (9 :1,12 mL), zinc dust (0.50g, 7.73 mmoles), Cui (0.45g, 2.38 mmoles), 3-bromo-1-propanol 14 (0.70g, 5.04 mmoles) in ethanol (2 mL) and 1-hexen-3-one 15 (0.33g, 3.36 mmoles) in ethanol (2 mL) at 0°C taken in a 30mL ultrasonic vessel was sonicated for 30 min. Usual work-up and purification over silica gel column chromatography (10% ethyl acetate in hexane) yielded pure 3 (0.29g, 54.72%); 1H NMR (CDCb): 0.90 (t, 1=6Hz, 3H, -CH2CH3), 1.50-1 .80 (m, 8H, methylene protons), 2.10 (t, 1=6Hz, 4H, -CH2CH2COCH2CHr), 3.30-3.70 (m, 3H, -CH2CH20H, -OH exchangeable with 0 20); IR (CCI4):3450-3300, 2920, 1720, 1210, 1160 (Found : C,68.07; H,1l.53. C9H, 802 requires C,68.35; H,1l.39%).

1-Iodo-2-(Z)-octene 17. 2-(Z)-Octen-1-ol 16 (1.15g, 8.99 mmoles) was subjected to iodination using anhyd. Nal (2.69g, 17.98 mmoles), boron trifluoride etherate (2.55g, 17.98 mmoles) in acetonitrile17 (40 mL) at 0°C. Usual work-up provided compound 17 (l.50g,70.09%); 1H NMR (CC14): 1.10 (t, 1=6Hz, 3H,-CH2CH3), 1.40-1.70 (m, 6H, methyl ene protons), l.90-2.30(m, 2H,-CH2CH2CH=), 3.90 (d , 1=6Hz, 2H, =CHCH21), 5.70-6.00 (m,2H vinylic protons) ;IR (neat) : 2980, 1660,725.

Methyl 5-(Z)-undecenoate 18. A mixture of ethanol-water (9: I , 12mL), zinc dust (0.30g, 4.62rnmoles) ,Cul(0.27g, 1.42mmoles) and compound 17 ( 1.85g,7.76mmoles) in ethanol (5mL) at 0°C taken

in a 30mL ultrasonic vessel was sonicated for 40 min . Usual work-up followed by silica gel column chromatography gave compound 18 (0.20g,68 .09%); 1H NMR ( CC14 ): l.OO(t, 1=6Hz,3H, -CH2CH3), 1.20-1.50 (m, 8H, methylene protons), 1.80-2.30 (m, 6H, 2x-CH2CH2C=, -CH2CH2CO-), 3.70 (s,3H ,-OCH3), 5.40-5 .70 (m, 2H, vinylic protons); IR (CCl4): 1750,1640,735.

5-(Z)-Undecenoic acid 4. Compound 18 (0.32, 1.62 mmoles) was hydrolysed 19 using potassium hydroxide (0.12g, 2.14mmoles) in ethanol (15 mL) under reflux for 2.5hr. Usual work-up of the reaction mixture provided compound 4 in 68% yield (0.20g) ; 1H NMR (CDC13): 1.00 (t, 1=6Hz,3H, -CH2CH3), 1.20-1.50 (m,8H,methylene protons), 1.80-2.30 (m,6H, 2 x -CH2CH2CH=, -CH2CH2CO-), 5.50-5.80 (m, 2H, vinylic protons); IR (CC14): 3200-2850, 1640, 735 (Found: C,71.51;H,ll.05. C11H200 2 requires C,71.74;H,10.87%).

2-Tridecanone 5. A mixture of ethanol-water (9 :1,15mL), zinc dust (0.51g,7.85mmoles). Cui (0.45g,2.37 mmoles), 1-iodononane 19 (1.28g, 5.04mmoles) in ethanol (2mL) and 3-buten-2-one 20 (0.24g, 3.43 mmoles) at 0°C taken in a 30mL ultrasonic vessel was sonicated for 30min. The usual work-up followed by silica gel column chromatography (5% ethyl acetate in hexane) provided compound 5 (0.42g,61.84%); 1H NMR (CCL4): 0.90(bs,11H, methylene protons),l.l0-1.60 (m,10H,methylene and methyl protons), 2.15(s,3H,CH3CO-), 2.45(t, 1=6Hz,2H,-CH2CH2CO-); IR (CCl4): 2920,1720,1210 (Found: C,78.88;H,13 .26 . C 13H260 requires C,78.79;H, 13.13%).

Acknowledgement Financial assistance for the work from CSIR and

UGC, New Delhi is highly acknowledged.

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