HK1078312B - Production of dihydronepetalactone by hydrogenation of nepetalactone - Google Patents

Description

Preparation of dihydronepetalactones by hydrogenation of nepetalactones

This application claims the benefit of U.S. provisional application No.60/369,470 filed on 3.4.2002, which is incorporated herein in its entirety as part of all of the subject matter herein.

Technical Field

The invention relates to a method for hydrogenating nepetalactones into dihydronepetalactones using a metal catalyst that is optionally supported on a carrier.

Background

Many plant species belonging to the family labiatae (Lamiaceae) produce essential oils (fragrance oils) useful as insect repellents and fragrance chemicals [ Hay, r.k.m and Svoboda, k.p. botanicals, "volatile oil crops: their biology, chemistry and production "(Botany," volume Oil crystals: the same biology, chemistry and production "); hay, r.k.m., Waterman, p.g. code; longman Group UK Co., Ltd (1993). Plants of the genus nepeta (nepeta) are included as an integral part of this family, and produce essential oils as a small commodity. This oil is very abundant in monoterpenoid compounds called Iridoids [ I novye, h., phytobiochemistry, irididoids method (irididoids. methods in Plant Biochemistry) 7: 99-143(1991) ], more specifically, to a compound obtained in The family Methylcyclopentanediol (Methylcyclopentanood) nepetalactone [ Clark, L.J., et al, Plant Journal, 11: 1387 to 1393(1997) and derivatives.

Four stereoisomers of nepetalactone are known to exist in nature and are readily available from different species in the plant genus nepeta. These chemicals have well-known stimulating effects on cats [ Tucker, a.o. and s.s.tucker. economic botanicals (economicbotanic), 42: 214 to 231(1988)), so that this oil-or more generally, hay of this plant, called cat nip (cat nip) -is used in cat toys. Leaves and oils of genus nepeta do not have a particularly attractive aroma. The use of such oils and grass is limited to the small market provided by domestic cat toys and accessories. A small share of the oils of the various genera of nepeta consists of dihydronepetalactones, which can be biosynthetically derived from the richer nepetalactones [ Regnier, f.e., et al, Phytochemistry (Phytochemistry) 6: 1281-1289 (1967); depooter, h.l. et al, flavor and Fragrance magazine (flavoured Fragrance Journal) 3: 155-; handjieva, n.v. and s.s.popov. journal of essential Oil research (j.essential Oil Res) 8: 639-643(1996)].

Iridoid monoterpenes have long been known to be effective repellents for a variety of insects [ Eisner, t. Science 146: 1318-1320 (1964); eisner, t. science 148: 966-968 (1965); coats, pesticide prospect (pesticide outlook) 12: 154 to 158 (2001); and Peterson, C.et al, American Chemical Society (Abstracts of Papers Chemical Society) (2001)222 (1-2): AGRO73 ]. However, few studies on the repellency of dihydronepetalactone have been conclusive [ Cavill, g.w.k. and d.v.clark, journal of insect physiology (j.insert Physiol) 13: 131 to 135 (1967); cavill, g.w.k. et al, tetrahedron, 38: 1931-1938 (1982); jefson, m, et al, journal of chemical Ecology (j.chemical Ecology) 9: 159 to 180 (1983). Recent studies have shown that dihydronepetalactones can exert a repellent effect on common pests of human society. Therefore, there is a need for dihydronepetalactone starting materials (or precursors) that can supply these compounds economically and in large quantities to enable commercial application of these molecules as insect repellents.

In addition, dihydronepetalactone compounds have been proposed as fragrance materials. In view of these considerations, there is also a need for dihydronepetalactone starting materials (or precursors) that are capable of supplying these compounds economically and in large quantities, in order to be able to use these molecules commercially as perfume materials.

A method of hydrogenating iridoid monoterpene lactones [ such as isonepetalactone, isodehydroformin, and isoactinidiolactone (isoactinoididalactone) using a platinum oxide (PtO2) catalyst has been reported [ Sakai, t. et al, japan chemical society of bulletin (fill. chem. soc. jan)53 (12): 3683-6(1980)]. Similarly, neonepetalactone and isonepetalactone are treated in Et₂In O using PtO₂Hydrogenation with Raney nickel in ethanol [ Sakai, T. et al, Koen Yoshishu-Koryo, Terepen oyobi Seiyu Kagaku ni Kansuru Toronkai, Vol.23 (1979) 45-48, publisher: hem, Soc, Japan, Tokyo, Japan]。

The preparation of dihydronepetalactones by hydrogenation of nepetalactones using a similar protocol is described in Regnier, r.e. Phytochemistry (Phytochemistry) 6: 1281 to 1289 (1967). Specifically, hydrogen and platinum oxide (PtO) are used₂) Processing nepetalactone to generate:

53% methyl 2-isopropyl-5-methylcyclopentanecarboxylate,

2.8% of alpha-dihydronepetalactone, and

35% delta-dihydronepetalactone.

Using a palladium catalyst (Pd/SrCO) supported on strontium carbonate₃) When it is generated

90% of alpha-dihydronepetalactone,

3% methyl 2-isopropyl-5-methylcyclopentane carboxylate and traces of delta-dihydronepetalactone.

However, both hydrogenation processes are limited, PtO₂Is a non-supported catalyst capable of forming a large number of ring-opened derivatives, and SrCO₃Is an expensive carrier.

There remains a need for an economical and efficient process for the preparation of dihydronepetalactones. The metals selected for use as catalysts in the process of the present invention provide the desired economics and production efficiencies, as well as a high degree of selectivity to dihydronepetalactone products.

Summary of The Invention

One embodiment of the present invention is a process for preparing dihydronepetalactone of formula (II) by hydrogenating nepetalactone of formula (I) in the presence of a catalytic metal other than nickel, platinum or palladium according to the following formula.

Another embodiment of the invention is a catalyst selected from the group consisting of nickel on a catalyst support, elemental platinum, platinum on a catalyst support, palladium unsupported on a catalyst support, and palladium supported on a non-SrCO₃A process for preparing dihydronepetalactone of formula (II) by hydrogenating nepetalactone of formula (I) in the presence of one or more catalytic metals constituting part of palladium on a catalyst support of (a).

Brief Description of Drawings

Figure 1 shows the chemical structure of a naturally occurring iridate (methylcyclopentadiene) nepetalactone.

Detailed Description

The term "nepetalactone" as used herein refers to a compound having the general structure as defined in formula (I).

Formula 1

Four stereoisomers of nepetalactone, as shown in figure 1, are known to exist in nature.

The term "dihydronepetalactone" or "mixture of dihydronepetalactones" as used herein refers to any mixture of dihydronepetalactone stereoisomers. The molar or mass composition of each of these isomers relative to the total dihydronepetalactone component is variable. Dihydronepetalactone is represented by formula 2:

formula 2

Where 4, 4a, 7 and 7a indicate 4 chiral centers of the molecule, the structure encompasses all possible stereoisomers of dihydronepetalactone.

The structure of dihydronepetalactone stereoisomers derivable from (7S) -nepetalactones is now shown below.

(1S, 5S, 9S, 6R) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

(1S, 9S, 5R, 6R) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

(1S, 5S, 9S, 6S) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

(1S, 9S, 6S, 5R) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

(9S, 5S, 1R, 6R) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

(9S, 1R, 5R, 6R) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

(9S, 6S, 1R, 5S) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

(9S, 6S, 1R, 5R) -5, 9-dimethyl-3-oxabicyclo [4.3.0]Nonan-2-ones

The term "catalyst" as used herein refers to a substance that affects the rate of chemical reaction (does not affect the equilibrium of the reaction) and that does not undergo a change in chemical composition as a result of the process.

The term "cocatalyst" as used herein is a compound added with the aim of enhancing the physical or chemical action of the catalyst. Chemical promoters generally increase the activity of the catalyst and may be incorporated into the catalyst at any stage of the chemical processing of the catalyst components. Chemical promoters generally enhance the physical or chemical action of the catalyst and can also be added to prevent undesirable side reactions. "Metal promoter" refers to a metal compound added to enhance the physical or chemical action of the catalyst.

Vitex lactone

Nepetalactone is a known material that can be conveniently obtained in relatively pure form from essential oils isolated by various means from plants of the genus nepeta (nepeta). Techniques for the separation of such oils are well known in the art and examples of oil extraction practices include, but are not limited to, steam distillation, organic solvent extraction, microwave assisted organic solvent extraction, supercritical fluid extraction, mechanical extraction, and cold absorption (primary cold extraction into fats followed by organic solvent extraction).

Essential oils isolated from different nepeta species are known to have different proportions of the naturally occurring individual nepetalactone stereoisomers [ Regnier, f.e., isophytochemistry 6: 1281-1289 (1967); depooter, h.l. et al, magazine of fragrances and perfumes 3: 155-159 (1988); hand jieva, n.v. and s.s.popov. journal of essential oil research 8: 6396-43(1996)]. Thus, hydrogenation of an oil containing a mixture of nepetalactones, obtained from any nepeta species, produces a mixture of dihydronepetalactone stereoisomers. Four chiral centers are present in the methylcyclopentadiene backbone of nepetalactone, at the 4, 4a, 7 and 7a carbons, as shown below:

thus, it is clear that after hydrogenation, a total of eight pairs of dihydronepetalactone enantiomers is possible. Among them, the naturally occurring stereoisomer described so far is (7S) -dihydronepetalactone.

Hydrogenation

Hydrogenation of nepetalactone is carried out in the presence of a suitable active metal hydrogenation catalyst. Generally, acceptable solvents, catalysts, equipment and procedures for hydrogenation are found in Augustine, synthetic chemist Heterogeneous Catalysis (heterogenous Catalysis for the synthetic chemist), Marcel Decker, new york, n.y. (1996).

A number of hydrogenation catalysts are effective, including (without limitation): containing as main components iridium, palladium, rhodium, nickel, ruthenium, platinum, rhenium, compounds thereof, combinations thereof and supported variants thereof.

The metal catalyst used in the process of the present invention may be used in the form of a catalyst supported on a carrier or unsupported. The supported catalyst is prepared by a process comprising: the active catalyst is deposited on the support by spraying, impregnation or physical mixing, and is then dried, calcined and, if desired, activated by methods such as reduction or oxidation. Materials often used as supports are porous solids having a high total surface area (both internal and external surface area) which can provide a high number of active sites per unit weight of catalyst. The catalyst carrier can improve the function of the catalyst; supported catalysts are generally preferred because active metal catalysts can be used more efficiently. The catalyst not supported on the catalyst support material is an unsupported catalyst.

The catalyst support can be any solid, inert material including, but not limited to, oxides such as silica, alumina, titania, calcium carbonate, barium sulfate, and carbon. The catalyst support can be in the form of powder, granules, pellets, and the like. Preferred support materials of the present invention are selected from the group consisting of carbon, alumina, silica-alumina, titania-alumina, titania-silica, barium, calcium, compounds thereof and groups thereofAnd (6) mixing. Suitable supports include carbon, SiO₂、CaCO₃、BaSO₄And Al₂O₃. However, the catalytic metals supported on the carrier may have the same carrier material or different carrier materials.

In one embodiment of the invention, a more preferred support is carbon. Further preferred carriers have a surface area ratio of 100 to 200²Those with large/g, in particular carbon. Even further preferred carriers are those having a surface area of at least 300m²Those per gram, in particular carbon.

Commercially available carbons that may be used in the present invention include those sold under the following trademarks:

Bameby & Sutcliffe^TM，Darco^TM，

Nuchar^TM，Columbia JXN^TM，Columbia LCK^TM，Calgon PCB^TM，

Calgon BPL^TM，Westvaco^TM，Norit^TMand Barnaby Cheny NB^TM. The carbon may also be a commercially available carbon, for example Calsicat C, Sibunit C or Calgon C (under the registered trade mark Centaur^®Commercially available).

Preferred catalytic metal and support system combinations include:

the nickel is supported on carbon and the nickel is supported on carbon,

nickel on Al₂O₃In the above-mentioned manner,

with nickel on CaCO₃In the above-mentioned manner,

nickel supported on BaSO₄In the above-mentioned manner,

nickel on SiO₂In the above-mentioned manner,

the platinum is supported on carbon in a manner such that,

platinum on Al₂O₃In the above-mentioned manner,

platinum on CaCO₃In the above-mentioned manner,

platinum carried in BaSO₄In the above-mentioned manner,

platinum carried on SiO₂In the above-mentioned manner,

the palladium is supported on carbon and the catalyst is,

palladium on Al₂O₃In the above-mentioned manner,

palladium on CaCO₃In the above-mentioned manner,

palladium on BaSO₄In the above-mentioned manner,

palladium on SiO₂In the above-mentioned manner,

the iridium is supported on carbon and the support is,

iridium supported on Al₂O₃In the above-mentioned manner,

iridium supported on SiO₂In the above-mentioned manner,

with iridium on CaCO₃In the above-mentioned manner,

iridium supported on BaSO₄In the above-mentioned manner,

the rhenium is supported on carbon in such a way that,

rhenium on Al₂O₃In the above-mentioned manner,

rhenium carried on SiO₂In the above-mentioned manner,

with rhenium on CaCO₃In the above-mentioned manner,

rhenium loaded in BaSO₄In the above-mentioned manner,

the rhodium is supported on carbon in a supported manner,

rhodium on Al₂O₃In the above-mentioned manner,

rhodium on SiO₂In the above-mentioned manner,

with rhodium on CaCO₃In the above-mentioned manner,

rhodium on BaSO₄In the above-mentioned manner,

the ruthenium is supported on carbon and the catalyst is a ruthenium-containing catalyst,

ruthenium onAl₂O₃In the above-mentioned manner,

with ruthenium on CaCO₃In the above-mentioned manner,

ruthenium on BaSO₄To a above, and

ruthenium on SiO₂The above.

As noted above, useful catalytic metals include the components iridium, palladium, rhodium, nickel, ruthenium, platinum, rhenium; useful carrier materials include carbon, alumina, silica-alumina, titania-alumina, titania-silica, barium, calcium, particularly carbon, SiO₂、CaCO₃、BaSO₄And Al₂O₃. The supported catalyst may be made from any combination of the above metals and support materials. However, the supported catalyst may also be made from various metals and/or combinations of various support materials selected from the aforementioned subclasses formed by omitting any one or more of the constituents of all groups set forth in the above list. As a result, the catalyst supported on the carrier, in this case, can be produced not only from one or more metals and/or support materials selected from any size of the subclasses that can be formed from all groups described in the above list, but also without the components of all groups omitted for forming the subclasses. In addition, a subclass formed by omitting different components from all groups in the above list may contain any number of components from all groups, such that those components from all groups that are excluded from forming the subclass are not present in the subclass. For example, in some cases it may be desirable to carry out the process in the absence of a catalyst formed from palladium on carbon.

Although the weight percent of catalyst on the support is not critical, it is understood that the higher the weight percent of metal, the faster the reaction. The preferred amount of metal in the supported catalyst ranges from about 0.1 wt% to about 20 wt% of the total supported catalyst (catalyst weight plus support weight). More preferably, the catalytic metal content ranges from about 1 wt% to about 10 wt% of the total supported catalyst. It is further preferred that the catalytic metal content range from about 3 wt% to about 7 wt% of the total supported catalyst.

Optionally, a metal promoter may be used with the catalytic metal in the process of the present invention. Suitable metal promoters include: 1) those of groups 1 and 2 of the periodic table; 2) tin, copper, gold, silver, and combinations thereof; and 3) a minor amount of a metal of group 8 of the periodic Table.

Temperature, solvent, catalyst, pressure and mixing rate are all parameters that affect hydrogenation. The relationship between these parameters can be adjusted to achieve the desired conversion, reaction rate and selectivity in the reaction of the process.

Within the scope of the present invention, the preferred temperature is from about 25 ℃ to 250 ℃, more preferably from about 50 ℃ to about 150 ℃, and most preferably from about 50 ℃ to 100 ℃. Preferably, the hydrogen pressure is from about 0.1 to about 20MPa, more preferably from about 0.3 to 10MPa, and most preferably from about 0.3 to 4 MPa. The reaction may be carried out neat or in the presence of a solvent. Useful solvents include those known in the hydrogenation art, for example, hydrocarbons, ethers, and alcohols. Most preferred are alcohols, especially lower alkanols such as methanol, ethanol, propanol, butanol and pentanol. When the reaction is carried out in accordance with a preferred embodiment, a selectivity of at least 70% is obtained, with a selectivity of at least 85% being typical. Selectivity is the weight percent of dihydronepetalactone conversion material, which is the portion of the starting material that precipitates during the hydrogenation reaction.

The process of the present invention may be carried out in any apparatus conventionally used for continuous processes, either batch, sequential batch (i.e., a series of batch reactors or in a continuous manner (see, e.g., h.s. fogler, basic Chemical reaction engineering, prence-Hall, inc., NJ, USA) the condensed water formed as a reaction product is removed by separation methods conventionally used for such separations.

After the hydrogenation reaction is complete, the resulting mixture of dihydronepetalactone isomer products can be separated by conventional means, for example, by distillation, by crystallization, or by preparative liquid chromatography to produce each of the highly pure dihydronepetalactone enantiomer pairs. Chiral chromatography can be used to separate enantiomers.

Examples

The present invention is further illustrated in detail by the following examples. These examples are given by way of illustration only, but are briefly describing a preferred embodiment of the present invention. From the above discussion and these examples, one skilled in the art can ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

The following abbreviations are used in the examples:

ESCAT is supplied by Engelhard corporation (E.Windsor, CT)

Catalyst series

Calsicat Carbon catalyst support from Engelhard

Sibunit Carbon catalyst support, available from Inst of Technical

Carbon(Omsk，Russia)

JM-A series carbon catalyst support, available from Johnson Matthey Inc

(W.Deptford，NJ)

Calgon Carbon catalyst support, available from Calgon company under the trade mark

Centaur®

DHNE dihydronepetalactone

NELA nepetalactone

GC gas chromatography

In addition, the pressure is expressed in units of psi and MPa, with 14.7psi equaling 0.101325MPa (both equaling latm).

Catalyst synthesis

Commercially available carriers such as carbon, alumina or silica (available from Engelhard corporation (e.windsor, CT)) are impregnated with incipient wetness with a metal salt. The precursors used were:

IrCl₃·3H₂O，

PdCl₂(Alfa Aesar，Wardhill，MA)，

RhCl₃·xH₂O(Alfa Aesar)，

RuCl₃·xH₂o (Aldrich Chemical Co., Milwaukee, Wis.),

AuCl₃·3H₂O(Alfa Aesar)，

NiCl₂·6H₂O(Alfa Aesar)，

H₂PtCl₆(Johnson Matthey corporation, W.Deptford, NJ),

and

Re₂O₇(Alfa Aesar).

drying the obtained sample, and carrying out H reaction at the temperature of 300-450 DEG C₂The reduction was carried out for 2 hours.

The carbons used are commercially available as Calsicat Carbon, Sibunit Carbon or Calgon Carbon. Calsicat Carbon is a public name by EngelhardS-96-140 lots supplied by department (Beachwood, OH). Sibunit Carbon is Sibunit-2 supplied by Institute of technical Carbon (5th Kordnaya, Omsk64418, Russia). Calgon Carbon is a PCB Carbon (under the registered trademark Centaur) supplied by Calgon Inc. (Pittsburgh, Pa.)^®Commercially available).

Experiments 1 to 46

This example describes a series of experiments to examine the ability of various catalysts to selectively convert nepetalactone to dihydronepetalactone via hydrogenation. The only items that varied in each experiment were the type of catalyst and support, but the following parameters were kept constant (unless specifically noted below):

time: the reaction time is 2 hours,

temperature: 50 deg.C

H₂Pressure: 700 psi; and

raw materials: 33% nepetalactone in ethanol.

These "standard" parameters were modified as follows:

experiments 11, 16, 20 and 22

Time: 4 hours;

experiment 17

Time: 3 hours;

H₂pressure: 1000 psi; and

raw materials: 50% nepetalactone in ethanol.

A33% or 50% solution of nepetalactone in ethanol, as indicated in the table below, the amount of catalyst and the support were charged to a 2ml pressure reactor. The reactor was sealed and charged with 2.75MPa of H₂And heating to a reaction temperature of 50 ℃. The pressure was maintained at the desired level during the reaction. The reaction was stopped after 2 hours and cooled. An internal standard (methoxyethyl ether) was added to the reaction product mixture.

The resulting reaction product mixture was analyzed by gas chromatography. HP-6890 GC used a Chrompack column (CP-WAX 58, 25 M.times.25 MM) and a flame ion detector. The temperature program was started at 50 ℃ and then heated to 80 ℃ at 5 ℃/min and then to 270 ℃ at 10 ℃/min. The column flow rate was 1.5cc/min He. The syringe and detector temperatures were 280 ℃ and 350 ℃, respectively. GC analysis enabled the determination of dihydronepetalactone selectivity [ DHNE Sel (%) ], Acid selectivity [ Acid Sel (%) ] and nepetalactone conversion [ NELA Con (%) ]. DHNE selectivity is the weight percent of dihydronepetalactone conversion feed, which is the portion of the starting material (by weight) that precipitates in the hydrogenation reaction. Acid selectivity is defined as the weight percent of conversion feed of the ring-opened product methyl 2-isopropyl-5-methylcyclopentanecarboxylate.

The following table (table 1) lists the catalysts, product selectivity, and reactant conversion for each experiment. The data presented show that the effect of each specific catalyst (variable support) is presented in batches.

TABLE 1

Hydrogenation of nepetalactone

Experimental number	Catalyst and process for preparing same	DHNE selectivity (%)	Acid selectivity (%)	NELA conversion (%)
					1	5％Ir/Al2O3	70.2	23.2	53.9
2	5％Ir/Calgon C	72.5	21.5	34.9
					3	5％Ir/Calsicat C	45.2	16.2	46.9
4	5％Ir/Sibunit C	72.8	25.3	49.3
					5	5％Ir/SiO2	77.9	19.5	95.3
6	5％Ni/Al2O3	12.1	0.0	6.2
					7	5％Ni/Calgon C	8.6	0.0	7.8
8	5％Ni/Calsicat C	10.8	0.0	5.8
					9	5％Ni/Sibunit C	74.6	0.0	0.7
10	5％Ni/SiO2	37.9	0.0	2.0
					11	5％Pd/Al2O3，JM-A22117-5	91.2	0.0	89.1
12	5％Pd/Al2O3，JM-A22117-5	83.8	0.0	99.9
					13	5％Pd/Al2O3，JM-A302099-5	81.7	0.0	99.9
14	5％Pd/Al2O3	78.7	17.0	99.5
					15	5％Pd/BaSO4，JM-A22222-5	92.1	0.0	98.8
16	5％Pd/BaSO4，JM-A22222-5	70.3	0.0	68.8
					17	5％Pd/C，JM-A503023-5	88.8	0.0	100.0
18	5％Pd/C，JM-A503023-5	80.0	13.8	100.0
					19	5％Pd/C，ESCAT-142	78.9	16.4	100.0
20	5％Pd/C，ESCAT-142	25.4	0.0	21.5
					21	5％Pd/CaCO3，JM-A21139-5	78.3	0.0	99.8
22	5％Pd/CaCO3，JM-A21139-5	71.2	0.0	65.7
					23	5％Pd/Calgon C	54.3	15.9	72.6
24	5％Pd/Calsicat C	73.9	13.2	94.7
					25	5％Pd/Sibunit C	60.7	18.0	69.9
26	5％Pd/SiO2	72.2	16.0	100.0
					27	5％Pt/Al2O3	13.7	54.0	100.0
28	5％Pt/Calgon C	26.1	68.0	66.9
					29	5％Pt/Calsicat C	15.4	54.6	79.9
30	5％Pt/Sibunit C	21.1	72.1	78.4
					31	5％Pt/SiO2	13.9	46.5	91.3
32	5％Re/Al2O3	61.8	0.0	0.4
					33	5％Re/Calgon C	12.8	0.0	1.8
34	5％Re/Calsicat C	15.5	3.9	33.6
					35	5％Re/Sibunit C	19.1	5.0	22.3
36	5％Re/SiO2	24.3	6.2	24.9
					37	5％Rh/Al2O3	82.2	15.6	99.9
38	5％Rh/Calgon C	80.3	12.1	99.1
					39	5％Rh/Calsicat C	68.6	12.2	98.4
40	5％Rh/Sibunit C	81.2	15.9	99.0
					41	5％Rh/SiO2	83.4	14.5	99.9

Experimental number	Catalyst and process for preparing same	DHNE selectivity (%)	Acid selectivity (%)	NELA conversion (%)
					42	5％Ru/Al2O3	67.0	11.2	91.5
43	5％Ru/Calgon C	36.6	7.6	73.1
					44	5％Ru/Calsicat C	41.0	6.8	69.6
45	5％Ru/Sibunit C	71.5	15.5	75.1
					46	5％Ru/SiO2	82.3	13.0	97.8

Preferred combinations of catalytic metals and support systems include:

Ir/C (Sibunit C, Calsicat C, and Calgon C),

Ir/Al₂O₃，

Ir/SiO₂，

Pd/C (Sibunit C, Calsicat C, Calgon C, JM-Aseries, and ESCAT-142),

Pd/Al₂O₃，

Pd/BaSO₄，

Pd/CaCO₃，

Pd/SiO₂，

Rh/C (Sibunit C, Calsicat C, and Calgon C),

Rh/Al₂O₃，

Rh/SiO₂，

Ru/C (Sibunit C, Calsicat C, and Calgon C),

Ru/Al₂O₃and are and

Ru/SiO₂.

for most experiments with these preferred combinations of catalytic metals and support systems, the yield of dihydronepetalactone was at least 70% selective. Experiment 15 used Pd/BaSO₄The yield of dihydronepetalactone is the highest (92.1%), and the conversion rate of nepetalactone is 98.8%.

Therefore, it was confirmed that various catalysts in which a group 8 metal was supported on various carriers were active for hydrogenation of nepetalactone, and high yields could be obtained over 2 to 4 hours. The present process results in a significant reduction in scale-up costs compared to hydrogenation processes previously reported in the literature for the preparation of dihydronepetalactones.

Claims (13)

1. A process for preparing dihydronepetalactone of formula (II), comprising: hydrogenation of nepetalactone of formula (I) in the presence of a supported metal catalyst according to the following formula:

wherein the catalytic metal is selected from the group consisting of nickel, platinum, palladium, iridium, rhenium, rhodium, ruthenium, and combinations thereof; and the carrier is selected from the group consisting of carbon, alumina, silica-alumina, titania-alumina, titania-silica, barium sulfate, calcium carbonate, and combinations thereof.

2. The process of claim 1 wherein the catalytic metal is present in the catalyst in an amount of from 0.1% to 20%.

3. The process of claim 1, carried out in the presence of a metal promoter.

4. The method of claim 3, wherein the metal promoter is selected from the group consisting of tin, copper, gold, silver, and combinations thereof.

5. The process of claim 1, which is carried out at a temperature of from 25 ℃ to 250 ℃ and a pressure of from 0.1MPa to 20 MPa.

6. The process of claim 1, wherein the process is carried out at a temperature of 50 ℃ to 150 ℃ and a pressure of 0.3MPa to 4 MPa.

7. The method of claim 1, wherein the catalytic metal and support are selected from the group consisting of

The nickel is supported on carbon and the nickel is supported on carbon,

nickel on Al₂O₃On the upper part

With nickel on CaCO₃In the above-mentioned manner,

nickel supported on BaSO₄In the above-mentioned manner,

nickel on SiO₂To a above, and

combinations thereof.

8. The method of claim 1, wherein the catalytic metal and support are selected from the group consisting of

The platinum is supported on carbon in a manner such that,

platinum on Al₂O₃In the above-mentioned manner,

platinum on CaCO₃In the above-mentioned manner,

platinum carried in BaSO₄In the above-mentioned manner,

platinum carried on SiO₂To a above, and

combinations thereof.

9. The method of claim 1, wherein the catalytic metal and support are selected from the group consisting of

The palladium is supported on carbon and the catalyst is,

palladium on Al₂O₃In the above-mentioned manner,

palladium on CaCO₃In the above-mentioned manner,

palladium on BaSO₄In the above-mentioned manner,

palladium on SiO₂To a above, and

combinations thereof.

10. The method of claim 1, wherein the catalytic metal and support are selected from the group consisting of

The iridium is supported on carbon and the support is,

iridium supported on Al₂O₃In the above-mentioned manner,

iridium supported on SiO₂In the above-mentioned manner,

with iridium on CaCO₃In the above-mentioned manner,

iridium supported on BaSO₄To a above, and

combinations thereof.

11. The method of claim 1, wherein the catalytic metal and support are selected from the group consisting of

The rhenium is supported on carbon in such a way that,

rhenium on Al₂O₃In the above-mentioned manner,

rhenium carried on SiO₂In the above-mentioned manner,

with rhenium on CaCO₃In the above-mentioned manner,

rhenium loaded in BaSO₄To a above, and

combinations thereof.

12. The method of claim 1, wherein the catalytic metal and support are selected from the group consisting of

The rhodium is supported on carbon in a supported manner,

rhodium on Al₂O₃In the above-mentioned manner,

rhodium on SiO₂In the above-mentioned manner,

with rhodium on CaCO₃In the above-mentioned manner,

rhodium on BaSO₄To a above, and

combinations thereof.

13. The method of claim 1, wherein the catalytic metal and support are selected from the group consisting of

The ruthenium is supported on carbon and the catalyst is a ruthenium-containing catalyst,

ruthenium on Al₂O₃In the above-mentioned manner,

with ruthenium on CaCO₃In the above-mentioned manner,

ruthenium on BaSO₄In the above-mentioned manner,

ruthenium on SiO₂To a above, and

combinations thereof.