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Synthesis of Nopinone from β-Pinene by Oxidative System ofRuCl3-NalO4-Phase Transfer CatalystYoshlfuml Yuasa a & Haruki Tsuruta aa Central Research Laboratory , Takasago InternationalCorporation , 1-4-11 Nishiyawata, Hiratsuka City, Kanagawa,254, JapanPublished online: 09 Dec 2011.

To cite this article: Yoshlfuml Yuasa & Haruki Tsuruta (1998) Synthesis of Nopinone from β-Pinene by Oxidative System of RuCl3-NalO4-Phase Transfer Catalyst, Journal of Essential OilResearch, 10:1, 39-42, DOI: 10.1080/10412905.1998.9700835

To link to this article: http://dx.doi.org/10.1080/10412905.1998.9700835

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J. Essent. Oil Res., 10, 39-42 (Jan/Feb 1998)

RESEARCH REPORT

Synthesis of Nopinone from P-Pinene by Oxidative System of RuCI,-Na104-Phase Transfer Catalyst

Yoshifumi Yuasa* and Haruki Tsuruta Central R e s e a d Laboratory, Takasago International Copra t ion

1-4-11 Ntsbiyawata, Hiratsuka City, Kanagawa, 254, Japan

Abstract Nopinone was synthesized from ppinene by an oxidative system of a RuC1,-

Nal0,-phase transfer catalyst in 89% yield. Using this oxidative system, a-fencho- camphorone and camphenilone were also synthesized from a-fenchene and camphene, in 75% and 78% yield, respectively.

Key Word Index Nopinone, p-pinene, oxidation, ruthenium chloride, sodium periodate, phase

transfer catalyst.

Introduction Nopinone [I] is a useful bicyclic monoterpene as a raw material for fragrance or flavor such as

cryptone [nl, nootkatone [III] and a-fenchol [IVI (1-3) (Figure 1). The synthesis of nopinone [I] by oxidation methods from P-pinene [Vl using ozone (4-8) or KMnO, (9) has been reported. However, p-pinene ozonide produced by ozone is a dangerous intermediate (lo), and the KMnO, oxidation method results in a low yield of nopinone and byproducts such as nopinonic acid. On the other hand, there are many synthetic methods using the oxidative cleavage of alkenes with an oxidant and catalytic ruthenium metal (ll), but few reports on the oxidative cleavage of cyclic alkenes to produce cyclic ketones (12). We have been studying the safe and facile oxidation of B-pinene M to produce nopinone [I], and we now report a synthesis of D] by an oxidative system of a RuCl3-Na1O,-phase transfer catalyst (PTC) (Figure 2). Using this oxidative system, other bicyclo monoterpenes, a-fenchene M and camphene m], were also oxidized to yield the corresponding a-fenchocamphorone [ W I and camphenilone [m, in 75% and 78% yield, respectively (Figure 3).

Experlrnental All chemicals were reagent grade and were used as received from the supplier. The IR was a Jasco

IR-810 and the NMR was a Bruker AM-400: The 'H- and "C-spectra were determined at 400 MHz and 100 MHz, respectively, and were recorded in CDC!, with TMS as the internal standard. The chemical shifts were given in 6 (ppm). MS: Hitachi M-80A mass spectrometer at 70 eV. Optical rotations: Jasco DIP-4 digital polarimeter. GC: HP 5890 with an FID detecter, column: fused silica NB-l(O.25 mm x 30 m, film thickness 0.4 pn); carrier gas N2, 1.0 kg/anz; oven temperature 7O0-20O0C (pmgrammed at 4"C/min);

R&&: Febnrary 1997 'Address for correspondence Recsiued: Novstnber 1996

1041-2905/98/0001-~39$04.00/0-01998 Allured Publishing Corp.

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40

II Figure 1. Structures of nopinone, cryptone, nootkatone and a-fenchol

Table 1. Oxidation of P-pinene [v] by the RuCI,a-Oxidant-PTC System

Reaction Product [I] PTC Temp. Time Conv.c Yieldd

Run Oxidantb Solvent (3 mol %) ("C) (h) ("/.I ("w 1 8eq.H,02 Acetone BTEAC 60 4 100 34

3 6eq.NaCIO CI(CH,),CI BTEAC r.t. 5 45 18 2 4eq.H,02 Acetone BTEAC 60 3 53 24

4 4eq.HI0, Hexane BTEAC r.t. 40 100 66 5 4eq.Nal0, AcOEt BTEAC r.t. 10 100 82 6 3eq.Nal0, AcOEt BTEAC r.t. 10 100 83 7 2ea.NalO. AcOEt BTEAC r.t. 10 85 76

1 mol % of RuCI. was used; HIO, and NalO. were dissolved in water, respectively; Conversion of [I] was determined by GC;

Table 11. The effect of PTC in the oxidation of O-dnene IV1

Product [I] Runa PTC Conv. (%)b Yield (%)c

1 No addition 49 38 2 n-Bu,NBr 91 83 3 n-Bu,NI 100 89 4 n-Bu,NCIO, 86 72 5 BnEt,NCI 90 80

7 n-Bu,PBr 96 87 8 BnPh,PCI 71 51

6 (n-Octyl),MeNCI 91 74

a Reaction conditions: M 23 mmol; R~C1~0 .23 mmol (1 mol %); PTC 0.69 mmol (3 mol %); NalO,70 mmol; AcOEt/H,O; r.t., 6h Conversion of [I] was determined by GC; 'Isolated yield.

injection temperature 250°C; detector temperature 250°C. Column chromatography: Merck Kieselgel 60, Art. -Nr. 7734. Melting points: Yanagimoto micro melting apparatus, uncorrected values. Boiling points: uncorrected values.

Syntbesis of (+I-Nopinone[Z]:To 30.8 g of (-)-P-pinene [Vl t226.5 mmol, purchased from Yasuhara Chemical Co. Ltd., with a purity of 98% according to GC, -20.6" (neat)], 470 mg (2.27 mmol) of ruthenium chloride, and 2.5 g (6.8 mmol) of tetra-n-butylammonium iodide in 250 mL of AcOEt, 145.5 g (680 mmol) of sodium periodate in 1.3 L of water was added dropwise for 3 h under ice cooling. After stirring at room temperature for 3 h, 250 mL of AcOEt was added to the reaction mixture. The organic layer was separated, washed with 500 mL of saturated NaCl and 500 mL of 10% Na,SO,, dried with anhydrous MgSO, and concentrated in vacuo to give an oil. The oil residue was distilled under reduced pressure to give 27.8 g of [I] as a colorless oil (89% yield). b.p. 8OoC/10 mmHg, [lit.(6).50-51~C/2 mmHg].

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Na104. cat.RuC13,

Figure 2. Synthesis of nopinone from p-pinene by the RuC1,-Nal0,-PTC

system

V ' I

Figure 3. Syntheses of a-fenchocam- phrone and camphenilone by the

RuC1,-Nal0,-PTC system

u VI

Vlll

Na104, cat. RuCI3,

cat. n-Bu4NI

75%

*

Na104, cat. RuCI3,

cat. n-Bu4NI -

78%

@To VII

a IX

= +18.3' (neat), [lit.(6), [a], = +17.4"1. The purity was 99.3% as determined by GC. IR (film): v = 1710 cm-'(C=O). 'H-NMR 0.86 (3H, s, CH,), 1.33 (3H, s, CH3), 1.58 (lH, d, J = 10.2 Hz), 1.91-2.06 (2H, m), 2.21-2.36 (2H, m), 2.51-2.63 (3H, m). ',C-NMR 21.4 (CH2), 22.1 (CH3), 25.3 (CH,), 25.8 (CH,) 32.8 (CH,), 40.4 (CH), 41.2 (C), 57.9 (CH), 214.9 (CO). MS ( d t , %): 138 (10) [M+], 122(15), 109(26); 95(46), 83(100), 54(80, 41(82), 39(84).

Syntbesfs of (-)-a-Fenebocampbore MI]: To 6.25 g of (+)-a-fenchene MI 146 mmol, produced by Takasago Int. Corp., with a purity of 99% according to GC, = +36.3" (neat)], 95 mg (0.46 mmol) of ruthenium chloride and 0.51 g (1.38 mmol) of tetra-n-butylammonium iodide in 50 mL of AcOEt, 30.0 g (140 mmol) of sodium periodate in 330 mL of water was added dropwise for 2 h under ice cooling. After stirring at room temperature for 4 h, 100 mL of AcOEt was added to the reaction mixture. The organic layer was separated, washed with 100 mL of saturated NaCl and 100 mL of 10% Na,SO,, dried with anhydrous MgSO, and concentrated in vacuo to give a solid. The crude solid was sublimated under reduced pressure to give 4.6 g of MI1 as colorless crystals (75% yield). m.p. 101'- 102"C, [lit.(l3), lO8"Cl. [a]: = -65.1" (EtOH, c = 2.01, [lit.(13), [a], = -60'1. The purity was 97.7% as determined by GC. IR (chloroform): v = 1740 cm-' (C=O). 'H-NMR 1.05 (6H, s, CH,), 1.38-1.51 (2H, m), 1.79(1H,d,J= 18.2Hz), 1.99-2.08(4H,m),2.38-2.44(1H,m).13C-NMR20.8(CH3),-21.7(CH3),22.8(CH3, 27.7 (CH,), 43.5 (CHI, 44.2 (CH,), 45.5 (C), 58.4 (CHI, 218.6 (CO). MS (42, %): 138 (23) [M+l, 123(2), 110(6), 95(18), 81(34), 69(100>, 55(18), 4N39).

S'tbesfs of (-)-Canrpbenflone[To 3.2 g of (-)-camphene [VJII] [23.5 mmol, purchased from Aldrich Chemical Campany, Inc., with a purity of 85% according to GC, [a]: = 48' (EtOH, c = 4.0)1,49 mg (0.23 mmol) of ruthenium chloride and 0.26 g (0.71 mmol) of tetra-n-butylammonium iodide in 30 mL of AcOEt, 15.1 g (70.5 mmol) of sodium periodate in 130 mL of water was added dropwise for 1 h at ice cooling. After stirring at room temperature for 5 h, 50 mL of AcOEt was added to the reaction mixture. The organic layer was separated, washed with 100 mL of saturated NaCl and 100 mL of 10% Na,SO,, dried with anhydrous MgSO, and concentrated in vacuo to give a solid. The crude solid was purified

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42 YUMA AND TSURUTA

by silica gel column chromatography using n-hexane as a eluent to give 2.3 g of [IX] as colorless crystals (78% yield). m.p. 38"-39"C, [lit.(14), 39"Cl. [a]: = -60.2" (benzene, c = 2.0), [lit.(14), [a], = -60.8', (benzene)]. The purity was 97% as determined by GC. IR (chloroform): v = 1740 cm-'(C=O). 'H-NMR 1.02 (3H, s, CH3), 1.05 (3H, s, CH,), 1.42-1.49 (2H, m), 1.56-1.65 (lH, m), 1.75-1.88 (2H, m), 1.96-1.99 (lH, m), 2.23 (lH, br.s), 2.55-2.57 (lH, m). l3C-NMR 21.4 (CH3), 23.1 (CH,), 23.2 (CH,), 24.5 (CH2), 35.0 (CH2), 46.1 (CHI, 46.9 (C), 50.1 (CHI, 222.7 (CO). MS ( d z , %): 138 (39) [M'l, 110(5), 95(4), 69(100>, 55(9), 4160).

Results and Discussion We have primarily examined the oxidation of P-pinene [Vl by excess H202 with a catalytic amount

of benzyltriethyl ammonium chloride (BTEAC), as the most available oxidant and PTC, in the presence of catalytic RuCJ (This oxidation did not proceed in the absence of RuC1,). However, as shown in Table I, the yield of nopinone [I] was too low because of many nonvolatile byproducts and also unsatisfactory in the case of NaClO as an oxidant. Finally, the best yield was obtained by the use of 3 mole equivalent of NaIO, in AcOEt (83%).

Next we have been investigated the effect of PTC on the oxidation of P-pinene. All of the PTCs showed good yield in comparison with the value obtained in the absence of PTC as shown in Table 11. In particuarly, the yield was improved by tetra-n-butylammonium iodide in 89%.

Using this oxidative system, we performed a safe and facile synthesis of nopinone [I]. We also applied this oxidative system to other cyclic monoterpenes which have a vinylidene bond, a-fenchene [VII and camphene [WIIl, and thus obtained a-fenchocamphorone [W] (75%) and camphenilone [IXI (78%), respectively (Figure 3).

Acknowledgment

of (-)-p-pinene.

References

We are grateful to the reviewer for drawing our attention to more recent references concerning the ozonolysis

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