Synthesis of the honey-bee attractant 13-hydroxy-2-oxotridecane

Article abstract of DOI:10.1023/A:1012351524532

13-Hydroxy-2-oxotridecane, which is isolated from extract of Evodia hupehensis Dode honey-bee eggs and actively attracts honey bees, is synthesized via ozonolysis of 1-methylcyclododecene and tetradec-13-en-2-one, the product from monoalkylation of the acetoacetic ester with 1-bromo-10-undecene followed by decarbethoxylation, with further reduction of the intermediate peroxides using NaBH(OAc)₃.

Full text of DOI:10.1023/A:1012351524532

Chemistry of Natural Compounds, Vol. 37, No. 2, 2001
SYNTHESIS OF THE HONEY-BEE ATTRACTANT
13-HYDROXY-2-OXOTRIDECANE
G. Yu. Ishmuratov,1 M. P. Yakovleva,1 R. Ya. Kharisov,1
O. V. Botsman,1 O. I. Izibairov,2 A. G. Mannapov,2
and G. A. Tolstikov1
UDC 542.943.5+547.451+632.936.2
13-Hydroxy-2-oxotridecane, which is isolated from extract of Evodia hupehensis Dode honey-bee eggs and
actively attracts honey bees, is synthesized via ozonolysis of 1-methylcyclododecene and tetradec-13-en-2-
one, the product from monoalkylation of the acetoacetic ester with 1-bromo-10-undecene followed by
decarbethoxylation, with further reduction of the intermediate peroxides using NaBH(OAc) .
3
Key words: bee attractant, acetoacetic ester, 1-bromo-10-undecene, 13-hydroxy-2-oxotridecane, bee, 1-
methylcyclododecene, ozonolysis, tetradec-13-en-2-one, sodium triacetoxyborohydride, synthesis.
13-Hydroxy-2-oxotridecane (1) is isolated from extract of Evodia hupehensis Dode honey-bee eggs and actively attracts
honey bees [1]. The synthesis of compound 1 via exhaustive ozonolysis of the double bonds in 2-methyl-1,13-tetradecadiene
(prepared via condensation of 10-undecenylbromide and methylallylchloride) followed by selective reduction by NaBH(OAc)
3
of the aldehyde function in the intermediate 12-oxotridecanal has been reported [2].
We developed new approaches to the synthesis of attractant 1. One of these is based on selective transformations of
the product from monoalkylation of the acetoacetic ester with 1-bromo-10-undecene (2) from undecylenic acid by the literature
method [3]. Decarbethoxylation of the unsaturated ketoester (3) under standard conditions [4] gives the key intermediate
tetradec-13-en-2-one [4), ozonolysis of which followed by reduction of the peroxide with NaBH(OAc) [5] avoids the preparation
3
of the unstable 12-oxotridecanal and increases the overall yield of compound 1 (calculated based on bromide 2) from 41 to 71%.
O
O
CO Et
2
LiI / DMF
OEt
Br
NaOEt- EtOH
2
3
O
1. O / AcOH-CH Cl
3
2
2
HO
2. NaBH(OAc)
4
O
O
O
3
1
1. O / AcOH-CH Cl
3
2
2
2. NaBH(OAc)
3
[6]
5
6
1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya
71, fax (3472) 35 60 66, kharis@anrb.ru; 2) Bashkir State Agrarian University, 450069, Ufa, ul. 50-let Oktyabrya, 34.
Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 165-166, March-April, 2001. Original article submitted March
23, 2001.
0009-3130/01/3702-0190$25.00 ©2001 Plenum Publishing Corporation
190

A shorter and effective synthesis of 1 uses ozonolysis of 1-methylcyclododecene (6), prepared from cyclododecanone
(5) according to the literature [6] and direct reduction of the peroxides using NaBH(OAc) . The yield was 98% based on starting
3
olefine 6.
EXPERIMENTAL
IR spectra were recorded on a UR-20 instrument as thin layers. NMR spectra were taken on a Bruker AM-300
spectrometer (working frequency 300.13 MHz for 1H and 75.47 MHz for 13C) in CDCl . The internal standard was chloroform
3
(impurity of protonated solvent in PMR, 7.27 ppm; in 13C NMR, the average CDCl signal at 77.00 ppm). Chromatography
3
was performed on a Chrom-5 instrument (column length, 1.2 m; stationary phase, SE-30 silicone (5%) on Chromaton N-AW-
DMCS, 0.16-0.20 mm), working temperature 50-300oC, He carrier gas. Analytical data corresponded to those calculated.
-3
Ethyl-2-acetyltridec-12-enoate (3). A solution of sodium ethylate [prepared from Na (0.85 g, 36.7·10 g-at) in
absolute EtOH (20 mL)] was treated under Ar at 20oC with acetoacetic ester (5.26 g, 40.4 mmole), heated to boiling, and treated
with bromide 2 (4.05 g, 17.4 mmole). The reaction mixture was boiled for 18 h (TLC monitoring), cooled, and filtered through
a Schott filter. The solid on the filter was washed with EtOH and evaporated. Yield of compound 3, 4.38 g (89%). IR spectrum
(KBr, , cm -1): 920, 1010 ( C–H), 1050, 1275 (C–O–C), 1645 (C C), 1715 (C O, ketone), 1750 (C O, ester), 3090 (CH CH ).
2
PMR spectrum (CDCl , , ppm, J/Hz): 1.30 (3H, t, J = 6.5, CH CH O), 1.20-1.40 (16H, m, H-3—H-10), 1.99 (2H, m, H-11),
3
3
2
2.18 (3H, s, H CCO), 3.33 (1H, t, J = 7.4, H-2), 4.15 (2H, q, J = 7.1, H CO), 4.85-5.00 (2H, m, H C ), 5.68-5.83 (1H, m, HC ).
3
2
2
13C NMR (CDCl ): 14.00 (q, H CCH O), 28.61 (q, H CCO), 27.28, 28.09, 28.81, 28.99, 29.06, 29.19, 29.34, 29.43
3
3
2
3
(t, C-3—C-10), 33.70 (t, C-11), 59.82 (d, C-2), 61.14 (t, CH O), 114.01 (t, C-13), 139.07 (d, C-12), 169.83 (s, C-1), 203.27
2
(s, H CCO).
3
Tetradec-13-en-2-one (4). A solution of ester 3 (2.65 g, 9.4 mmole) in absolute DMF (27 mL) at room temperature
was treated with LiI (3.27 g, 24.4 mmole), boiled until CO evolution ceased (~12 h), cooled, extracted with methyl-t-butylether
2
(200 mL), washed successively with saturated Na S O and NaCl solutions, dried over Na SO , and evaporated. Yield of enone
2 2
3
2
4
4, 1.60 g (81%). IR spectrum (KBr, , cm -1): 920, 1010 ( C–H), 1650 (C C), 1720 (C O), 3020, 3090 (CH CH ). PMR
2
spectrum (CDCl , , ppm, J/Hz): 1.22 (16H, br. s, H-4—H-11), 1.98 (2H, m, H-12), 2.08 (3H, s, H CCO), 2.37 (2H, t, J = 7.3,
3
3
H-3), 4.83-4.98 (2H, m, H C ), 5.68-5.84 (1H, m, HC ).
2
13C NMR (CDCl ): 25.20 (t, C-4), 28.73, 29.10, 29.16, 29.18, 29.21, 29.26, 29.32 (t, C-5—C-11), 29.65 (q, C-1), 33.66
3
(t, C-12), 43.63 (t, C-3), 113.95 (t, C-14), 139.03 (d, C-13), 209.04 (s, C-2).
13-Hydroxy-2-oxotridecane (1). a. An ozone—oxygen mixture (ozonator production, 40 mmole O /h) was bubbled
3
through a solution of olefine 4 (1.25 g, 14.4 mmole) and glacial AcOH (1.72 g, 28.7 mmole) in CH Cl (40 mL) that was stirred
2
2
at -4 to -2oC until 15 mmole of ozone was absorbed. The reaction mixture was purged with Ar, diluted with CH Cl (20 mL),
2
2
and treated with stirring (10oC) with a previously prepared suspension of NaBH(OAc) [prepared by treating a solution of glacial
3
AcOH (11.9 g, 198.0 mmole) in CH Cl (20 mL) with a suspension of NaBH (2.5 g, 66.0 mmole) in CH Cl (100 mL) followed
2
2
4
2
2
by stirring for 2 h]. The reaction mixture was heated to room temperature, stirred for 3 h, cooled to 10oC, and treated with
NaOH solution (4.5 g in 100 mL water). The organic layer was separated, washed successively with saturated NH Cl solution
4
and water, dried over Na SO , and evaporated. Yield of 1, 1.25 g (98%), mp 54.0-54.5oC [2].
2
4
IR and PMR spectra were identical to those reported in the literature [2]. 13C NMR spectrum (CDCl ): 23.68 (t, C-10),
3
25.63 (t, C-3), 28.98, 29.21, 29.26, 29.26, 29.34, 29.41 (t, C-4—C-9), 29.67 (q, C-1), 32.58 (t, C-2), 43.67 (t, C-12), 62.69 (t,
C-1), 209.56 (s, C-13).
b. Ozonolysis of cycloolefine 6 (1.00 g, 5.55 mmole) under the conditions described above gave 1 (1.06 g, 89%)
identical to that obtained from experiment a.
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