Halogenated acetaldehyde acetal compounds and methods of making and methods of making (2-cyclopentenyl) acetate and acetic compounds therefrom

Abstract

The present invention relates to a process for the preparation of a (2-cyclopentenyl)acetic acid ester compound (2): wherein R represents a linear or branched alkyl group having 1 to 4 carbon atoms, Y represents a halogen atom, and X1 to X7 independently of one another represent a hydrogen atom or a methyl group, with the proviso that one to three of X1 to X7 represent a methyl group and the others represent a hydrogen atom, which comprises: subjecting a haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1): wherein R is as defined above, X1 to X7 are as selected in general formula (2) respectively, and Y represents a halogen atom, to a dehydrohalogenation in the presence of a base, followed by a rearrangement to form compound (2); the present invention also relates to a process for the preparation of a (2-cyclopentenyl)acetic acid compound (3): wherein X1 to X7 are as selected in general formula (1) respectively, which comprises: hydrolyzing compound (2) to form compound (3); the present invention also relates to a novel compound (1).

Description

Technical Field

[0001] This invention relates to a novel compound, a haloacetal alkyl 2-cyclopentenyl acetal, and a method for preparing the same. The invention also relates to a method for preparing (2-cyclopentenyl)acetic acid ester compounds from the same compound, and a method for preparing (2-cyclopentenyl)acetic acid compounds from the same compound. Background Technology

[0002] Mealybugs are pests belonging to the family Mealycidae in the order Hemiptera. They suck the sap from many agricultural plants (such as grapes, apples, pears, persimmons, pineapples, bananas, coffee, citrus fruits, and flowering plants), thus damaging these crops. Furthermore, mealybugs secrete honeydew, which contains sugar, leading to fungal diseases. These damages and diseases reduce the yield and quality of these agricultural plants, posing a serious problem.

[0003] Insecticides are commonly used to control mealybugs. However, mealybugs live in narrow spaces behind leaves and / or plant bark, and are covered in a waxy substance. Therefore, insecticides have difficulty coming into contact with the pests' bodies, resulting in insufficient effectiveness.

[0004] Given the adverse environmental and human health effects of pesticides, there is a growing need to develop new, highly safe, and eco-friendly control methods, such as using insect sex pheromones to disrupt mating and / or mass trapping. Developing such new control methods requires the industrial and inexpensive production of large quantities of sex pheromones.

[0005] Regarding the sex pheromones of mealybugs, the chemical structures of sex pheromones secreted by approximately 20 agricultural pests have been identified. Some of these sex pheromones are known to have characteristic structures in which the cyclopentane or cyclopentene ring is substituted with an alkyl group, and a 2-acyloxyethyl group or a formylmethyl group is attached to the ring.

[0006] Specifically, the sex pheromone of the long-tailed mealybug (Pseudococcus longispinus) has been reported to be an optically active (-)-2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (Non-Patent Literature 1 listed below). The sex pheromone of the sexually reproduced pineapple mealybug (Dysmicoccus brevipes) has been reported to be an optically active (1S,2S)-(-)-(1,2-dimethyl-3-methylenecyclopentyl)acetaldehyde (Non-Patent Literatures 2 and 3 listed below).

[0007] It has been reported that the enantiomers or diastereomers (i.e., various stereoisomers) of this optically active sex pheromone have no adverse effect on the attraction activity of natural pheromones (Non-Patent Literature 1 and 3). Therefore, in order to establish a technology for controlling pests using sex pheromones, considering the inexpensive supply of pheromone substances and economical control methods, it is considered effective to find a method for preparing a mixture of stereoisomers containing natural pheromones.

[0008] Methods for preparing mixtures of stereoisomers of these pheromones are reported below. For example, a mixture containing stereoisomers of (-)-2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (a sex pheromone substance of the long-tailed mealybug) is prepared as follows: 3,4,4-trimethyl-2-cyclopenten-1-ol is acetylated, the reaction product is reacted with a base and then with tert-butyldimethylchlorosilane, and the reaction product is subjected to an Ireland-Claisen rearrangement to form (1,5,5-trimethyl-2-cyclopentenyl)acetic acid as an intermediate, and then the functional group of the intermediate is converted into the target functional group (Non-Patent Literature 4 listed below).

[0009] A mixture of stereoisomers containing (1S,2S)-(-)-(1,2-dimethyl-3-methylenecyclopentyl)acetaldehyde (the sex pheromone of the pineapple mealybug) was prepared as follows: 2,3-dimethyl-2-cyclopenten-1-ol was acetylated, the reaction product was reacted with a base and then with trimethylchlorosilane, and the reaction product was subjected to the Eland-Claisen rearrangement to form (1,2-dimethyl-2-cyclopentenyl)acetic acid as an intermediate. The skeleton of the intermediate was converted to the skeleton of the target compound, and then the functional groups in the resulting compound were converted to the target functional groups to obtain a mixture of enantiomers and / or diastereomers (Non-Patent Literature 5 listed below).

[0010] Similar to the aforementioned Eland-Claisen rearrangement, the Johnson-Claisen rearrangement is referred to as the Claisen-type rearrangement of allyl alcohols (such as 2-cyclopenten-1-ol compounds), in which 2-cyclopenten-1-ol compounds react with trialkyl orthoacetate in the presence of a weakly acidic catalyst (such as propionic acid) to form (2-cyclopentenyl)acetate compounds (Non-Patent Literature 6 listed below).

[0011] List of Literature

[0012] [Non-patent literature]

[0013] [Non-patent literature 1] R. Ramesh et al., J. Org. Chem., 2013, 78, 6281-6284.

[0014] [Non-Patent Literature 2] J. Tabata et al., JRSoc. Interface, 14 (2017), a copy of which can be downloaded from the following website: URL https: / / royalsocietypublishing.org / doi / 10.1098 / rsif.2017.0027.

[0015] [Non-Patent Literature 3] K. Mori et al., Tetrahedron, 73(2017)6530-6541.

[0016] [Non-patent literature 4] JGMillar et al., Synlett, 15(2010)2319-2321.

[0017] [Non-Patent Literature 5] K. Mori et al., Tetrahedron, 72(2016)6578-6588.

[0018] [Non-Patent Literature 6] W.S. Johnson et al., J. Am. Chem, Soc., 92 (1970) 741-743.

[0019] The problem to be solved by this invention

[0020] As mentioned above, (2-cyclopentenyl)acetic acid compounds are a useful synthetic intermediate in all the literature for the preparation of the envisioned sex pheromones of mealybugs. It is necessary to establish a method for the industrial and inexpensive preparation of (2-cyclopentenyl)acetic acid ester compounds and (2-cyclopentenyl)acetic acid compounds.

[0021] However, the preparation methods using the Elland-Claisen rearrangement reaction described in Non-Patent Literature 4 and Non-Patent Literature 5 have the disadvantages of using flammable organolithium compounds and lithium amines; the reaction must be carried out at extremely low temperatures down to -78°C; and the use of trialkylsilane chlorides, which are relatively expensive in industry.

[0022] In the method for preparing (2-cyclopentenyl)acetic acid esters via the Johnson-Clayson rearrangement reaction described in Non-Patent Literature 6 (wherein the 2-cyclopenten-1-ol compound reacts with a trialkyl orthoacetate in the presence of a weakly acidic catalyst), the dehydration reaction of the starting material 2-cyclopenten-1-ol compound occurs preferentially, leading to problematic low yields (see Non-Patent Literature 4 and Comparative Examples 1 and 2 described in this specification). Therefore, the prior art has failed to industrialize and economically produce (2-cyclopentenyl)acetic acid ester compounds and (2-cyclopentenyl)acetic acid compounds in large quantities. Summary of the Invention

[0023] The present invention was made under these circumstances with the aim of overcoming the aforementioned problems of the prior art and providing a novel starting material compound for the preparation of (2-cyclopentenyl)acetic acid ester compounds and (2-cyclopentenyl)acetic acid compounds, which are intermediates for the preparation of mealybug pheromones.

[0024] The present invention also aims to overcome the above-mentioned problems of the prior art and to provide an industrial and economical method for preparing (2-cyclopentenyl)acetic acid ester compounds and an industrial and economical method for preparing (2-cyclopentenyl)acetic acid compounds, both of which are intermediates for preparing mealybug pheromones.

[0025] Through in-depth research, the inventors now provide a haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (a novel compound) and have discovered that by subjecting the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound to a dehydrogenation halogenation reaction in the presence of a base followed by a rearrangement reaction, (2-cyclopentenyl) acetate compounds can be prepared within an industrially readily applicable reaction temperature range without the use of flammable and industrially expensive starting materials.

[0026] The inventors also discovered that the (2-cyclopentenyl)acetic acid compounds prepared by hydrolysis can be used to prepare (2-cyclopentenyl)acetic acid compounds efficiently and industrially, thus completing this invention.

[0027] According to one aspect of the present invention, the present invention provides a method for preparing (2-cyclopentenyl)acetic acid ester compounds of the following general formula (2):

[0028]

[0029] Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and X1 to X7 independently represent hydrogen atoms or methyl groups, provided that one to three of X1 to X7 represent methyl groups and the rest represent hydrogen atoms.

[0030] The method includes:

[0031] Haloacetal alkyl 2-cyclopentenyl acetals of the following general formula (1):

[0032]

[0033] Where R is defined as above, X1 to X7 are selected as in general formula (2), and Y represents a halogen atom.

[0034] The dehydrohalogenation reaction is carried out in the presence of a base, followed by a rearrangement reaction to form (2-cyclopentenyl)acetic acid ester compound (2).

[0035] According to another aspect of the present invention, the present invention provides a method for preparing (2-cyclopentenyl)acetic acid compounds of the following general formula (3):

[0036]

[0037] Where X1 to X7 are selected as in general formula (1),

[0038] The method includes:

[0039] The aforementioned method for preparing (2-cyclopentenyl)acetic acid compound (2); and

[0040] Hydrolyze (2-cyclopentenyl)acetic acid ester compound (2) to form (2-cyclopentenyl)acetic acid compound (3).

[0041] According to another aspect of the present invention, the present invention provides a method for preparing alkyl 2-cyclopentenyl acetal compounds of the following general formula (1):

[0042]

[0043] Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, X1 to X7 independently represent hydrogen atoms or methyl groups, provided that one to three of X1 to X7 represent methyl groups and the rest represent hydrogen atoms, and Y represents a halogen atom.

[0044] The method includes:

[0045] Halogenating alkyl vinyl ether compounds of the following general formula (4) with a halogenating agent to form halides;

[0046]

[0047] Where R is as defined above, and

[0048] The halide is subjected to a substitution reaction with a 2-cyclopenten-1-ol compound of the following general formula (5):

[0049]

[0050] Where X1 to X7 are selected as in general formula (1),

[0051] To form a haloacetal alkyl 2-cyclopentenyl acetal compound (1).

[0052] According to another aspect of the present invention, the present invention provides a method for preparing (2-cyclopentenyl)acetic acid ester compounds of the following general formula (2):

[0053]

[0054] Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and X1 to X7 are selected as in general formula (1),

[0055] The method includes:

[0056] The aforementioned method for preparing haloacetaldehyde alkyl 2-cyclopentenyl acetal compounds (1); and

[0057] The alkyl 2-cyclopentenyl acetal compound (1) of haloacetaldehyde was subjected to dehydrohalogenation in the presence of a base, followed by a rearrangement reaction to form (2-cyclopentenyl) acetate compound (2).

[0058] According to another aspect of the present invention, the present invention provides a method for preparing (2-cyclopentenyl)acetic acid compounds of the following general formula (3):

[0059]

[0060] Where X1 to X7 are selected as in general formula (1),

[0061] The method includes:

[0062] The aforementioned method for preparing (2-cyclopentenyl)acetic acid compound (2); and

[0063] Hydrolyze (2-cyclopentenyl)acetic acid ester compound (2) to form (2-cyclopentenyl)acetic acid compound (3).

[0064] According to another aspect of the present invention, the present invention provides a haloacetal alkyl 2-cyclopentenyl acetal compound of the following general formula (1):

[0065]

[0066] Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, X1 to X7 represent hydrogen atoms or methyl groups independently of each other, provided that one to three of X1 to X7 represent methyl groups and the rest represent hydrogen atoms, and Y represents a halogen atom.

[0067] According to the present invention, a novel compound (1) is provided: a haloacetaldehyde alkyl 2-cyclopentenyl acetal.

[0068] According to the present invention, (2-cyclopentenyl)acetal compound (1) can be used as a starting material to prepare (2-cyclopentenyl)acetate compound (2) within an industrially applicable reaction temperature range without the use of flammable and industrially expensive starting materials. This is an effective and useful intermediate for the preparation of mealybug pheromones.

[0069] According to the present invention, (2-cyclopentenyl)acetic acid compound (3) can also be prepared industrially and economically by hydrolyzing the (2-cyclopentenyl)acetic acid ester compound (2) thus prepared.

[0070] The novel compound haloacetal alkyl 2-cyclopentenyl acetal (1) can also be used as an intermediate in the preparation of prostaglandin analogs. Detailed Implementation

[0071] The embodiments of the present invention will now be described in detail. It should be noted that the present invention is not limited to, nor is it restricted by, the embodiments described herein.

[0072] A. The following describes a novel compound of general formula (1), a haloacetal alkyl 2-cyclopentenyl acetal.

[0073]

[0074] In general formula (1), R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms. Examples of alkyl groups include straight-chain alkyl groups such as methyl, ethyl, n-propyl, and n-butyl groups; and branched alkyl groups such as isopropyl and isobutyl groups. Methyl, ethyl, and n-propyl groups are preferred from the perspective of reactivity and / or yield.

[0075] In general formula (1), X1 to X7 represent hydrogen atoms or methyl groups independently of each other, provided that one to three of X1 to X7 represent methyl groups and the rest represent hydrogen atoms.

[0076] When one of X1 to X7 is a methyl group, any one of X1, X2, X3, X4, X5, X6, and X7 is a methyl group. For example, in Examples 1-7 described below, X2 is a methyl group, and the rest represent hydrogen atoms.

[0077] In the case where two of X1 to X7 represent methyl groups, when X1 is a methyl group, any one of X2, X3, X4, X5, X6, and X7 is a methyl group; when X2 is a methyl group, any one of X1, X3, X4, X5, X6, and X7 is a methyl group; when X3 is a methyl group, any one of X1, X2, X4, X5, X6, and X7 is a methyl group; when X4 is a methyl group, any one of X1, X2, X3, X5, X6, and X7 is a methyl group; when X5 is a methyl group, any one of X1, X2, X3, X4, X6, and X7 is a methyl group; when X6 is a methyl group, any one of X1, X2, X3, X4, X5, and X7 is a methyl group; and when X7 is a methyl group, any one of X1, X2, X3, X4, X5, and X6 is a methyl group. For example, in Examples 1-5 described below, X1 and X2 represent methyl groups, and the remainder represent hydrogen atoms; in Examples 1-6 described below, X5 and X6 represent methyl groups, and the remainder represent hydrogen atoms.

[0078] In the case where three of X1 to X7 represent methyl groups, when X1 and X2 represent methyl groups, any one of X3, X4, X5, X6, and X7 is a methyl group; when X1 and X3 represent methyl groups, any one of X2, X4, X5, X6, and X7 is a methyl group; when X1 and X4 represent methyl groups, any one of X2, X3, X5, X6, and X7 is a methyl group; when X1 and X5 represent methyl groups, any one of X2, X3, X4, X6, and X7 is a methyl group; when X1 and X6 represent methyl groups, any one of X2, X3, X4, X5, and X7 is a methyl group; when X1 and X7 represent methyl groups, any one of X2, X3, X4, X5, and X6 is a methyl group; all other combinations besides the above three methyl groups are also possible. For example, in Examples 1-1, 1-2, 1-3 and 1-4, X2, X3 and X4 represent methyl groups, and the rest represent hydrogen atoms.

[0079] In another embodiment, X7 of X1 to X7 is preferably a hydrogen atom.

[0080] In another embodiment, in particular, X1 and X7 of X1 to X7 preferably represent hydrogen atoms. More preferably, X1, X5, X6 and X7 represent hydrogen atoms, and X2, X3 and X4 represent methyl groups (see Examples 1-1, 1-2, 1-3 and 1-4 below).

[0081] In another embodiment, in particular, X4 and X7 of X1 to X7 preferably represent hydrogen atoms. Preferably, X3, X4, X5, X6, and X7 represent hydrogen atoms, and X1 and X2 represent methyl groups (see Examples 1-5 below). Alternatively, X1, X3, X4, X5, X6, and X7 preferably represent hydrogen atoms, and X2 represents a methyl group (see Examples 1-7 below).

[0082] In general formula (1), Y represents a halogen atom. Examples of halogen atoms include chlorine, bromine, and iodine atoms. From the perspective of reactivity and / or yield, bromine or iodine atoms are preferred.

[0083] Examples of alkyl 2-cyclopentenyl acetal compounds of haloacetaldehyde (1) include the following compounds:

[0084] Chloroacetaldehyde straight-chain alkyl-2-cyclopentenyl acetals, such as chloroacetaldehyde methyl 3-methyl-2-cyclopentenyl acetal, chloroacetaldehyde ethyl 3-methyl-2-cyclopentenyl acetal, chloroacetaldehyde 3-methyl-2-cyclopentenyl n-propyl acetal, chloroacetaldehyde n-butyl 3-methyl-2-cyclopentenyl acetal, chloroacetaldehyde methyl 5-methyl-2-cyclopentenyl acetal, chloroacetaldehyde ethyl 5-methyl-2-cyclopentenyl acetal, chloroacetaldehyde 5-methyl-2-cyclopentenyl n-propyl acetal, and chloroacetaldehyde n-butyl 5-methyl-2-cyclopentenyl acetal;

[0085] Bromoacetaldehyde straight-chain alkyl-2-cyclopentenyl acetals, such as bromoacetaldehyde methyl 3-methyl-2-cyclopentenyl acetal, bromoacetaldehyde ethyl 3-methyl-2-cyclopentenyl acetal, bromoacetaldehyde 3-methyl-2-cyclopentenyl n-propyl acetal, bromoacetaldehyde n-butyl 3-methyl-2-cyclopentenyl acetal, bromoacetaldehyde methyl 5-methyl-2-cyclopentenyl acetal, bromoacetaldehyde ethyl 5-methyl-2-cyclopentenyl acetal, bromoacetaldehyde 5-methyl-2-cyclopentenyl n-propyl acetal, and bromoacetaldehyde n-butyl 5-methyl-2-cyclopentenyl acetal;

[0086] Iodoacetaldehyde straight-chain alkyl-2-cyclopentenyl acetals, such as iodoacetaldehyde methyl 3-methyl-2-cyclopentenyl acetal, iodoacetaldehyde ethyl 3-methyl-2-cyclopentenyl acetal, iodoacetaldehyde 3-methyl-2-cyclopentenyl n-propyl acetal, iodoacetaldehyde n-butyl 3-methyl-2-cyclopentenyl acetal, iodoacetaldehyde methyl 5-methyl-2-cyclopentenyl acetal, iodoacetaldehyde ethyl 5-methyl-2-cyclopentenyl acetal, iodoacetaldehyde 5-methyl-2-cyclopentenyl n-propyl acetal, and iodoacetaldehyde n-butyl 5-methyl-2-cyclopentenyl acetal;

[0087] Chloroacetaldehyde branched alkyl monomethyl-2-cyclopentenyl acetals, such as chloroacetaldehyde isopropyl 3-methyl-2-cyclopentenyl acetal, chloroacetaldehyde isobutyl 3-methyl-2-cyclopentenyl acetal, chloroacetaldehyde isopropyl 5-methyl-2-cyclopentenyl acetal, and chloroacetaldehyde isobutyl 5-methyl-2-cyclopentenyl acetal;

[0088] Bromoacetaldehyde branched alkyl monomethyl-2-cyclopentenyl acetals, such as bromoacetaldehyde isopropyl 3-methyl-2-cyclopentenyl acetal, bromoacetaldehyde isobutyl 3-methyl-2-cyclopentenyl acetal, bromoacetaldehyde isopropyl 5-methyl-2-cyclopentenyl acetal, and bromoacetaldehyde isobutyl 5-methyl-2-cyclopentenyl acetal;

[0089] Iodoacetaldehyde branched alkyl monomethyl-2-cyclopentenyl acetals, such as iodoacetaldehyde isopropyl 3-methyl-2-cyclopentenyl acetal, iodoacetaldehyde isobutyl 3-methyl-2-cyclopentenyl acetal, iodoacetaldehyde isopropyl 5-methyl-2-cyclopentenyl acetal, and iodoacetaldehyde isobutyl 5-methyl-2-cyclopentenyl acetal;

[0090] Chloroacetaldehyde straight-chain alkyl dimethyl-2-cyclopentenyl acetals, such as chloroacetaldehyde 2,3-dimethyl-2-cyclopentenyl methyl acetal, chloroacetaldehyde 2,3-dimethyl-2-cyclopentenyl ethyl acetal, chloroacetaldehyde 2,3-dimethyl-2-cyclopentenyl n-propyl acetal, chloroacetaldehyde n-butyl 2,3-dimethyl-2-cyclopentenyl acetal, chloroacetaldehyde 5,5-dimethyl-2-cyclopentenyl methyl acetal, chloroacetaldehyde 5,5-dimethyl-2-cyclopentenyl ethyl acetal, chloroacetaldehyde 5,5-dimethyl-2-cyclopentenyl n-propyl acetal, and chloroacetaldehyde n-butyl 5,5-dimethyl-2-cyclopentenyl acetal;

[0091] Bromoacetaldehyde straight-chain alkyl dimethyl-2-cyclopentenyl acetals, such as bromoacetaldehyde 2,3-dimethyl-2-cyclopentenyl methyl acetal, bromoacetaldehyde 2,3-dimethyl-2-cyclopentenyl ethyl acetal, bromoacetaldehyde 2,3-dimethyl-2-cyclopentenyl n-propyl acetal, bromoacetaldehyde n-butyl 2,3-dimethyl-2-cyclopentenyl acetal, bromoacetaldehyde 5,5-dimethyl-2-cyclopentenyl methyl acetal, bromoacetaldehyde 5,5-dimethyl-2-cyclopentenyl ethyl acetal, bromoacetaldehyde 5,5-dimethyl-2-cyclopentenyl n-propyl acetal, and bromoacetaldehyde n-butyl 5,5-dimethyl-2-cyclopentenyl acetal;

[0092] Iodoacetaldehyde straight-chain alkyl dimethyl-2-cyclopentenyl acetals, such as iodoacetaldehyde 2,3-dimethyl-2-cyclopentenyl methyl acetal, iodoacetaldehyde 2,3-dimethyl-2-cyclopentenyl ethyl acetal, iodoacetaldehyde 2,3-dimethyl-2-cyclopentenyl n-propyl acetal, iodoacetaldehyde n-butyl 2,3-dimethyl-2-cyclopentenyl acetal, iodoacetaldehyde 5,5-dimethyl-2-cyclopentenyl methyl acetal, iodoacetaldehyde 5,5-dimethyl-2-cyclopentenyl ethyl acetal, iodoacetaldehyde 5,5-dimethyl-2-cyclopentenyl n-propyl acetal, and iodoacetaldehyde n-butyl 5,5-dimethyl-2-cyclopentenyl acetal;

[0093] Chloroacetaldehyde branched alkyl dimethyl-2-cyclopentenyl acetals, such as chloroacetaldehyde 2,3-dimethyl-2-cyclopentenyl isopropyl acetal, chloroacetaldehyde 2,3-dimethyl-2-cyclopentenyl isobutyl acetal, chloroacetaldehyde 5,5-dimethyl-2-cyclopentenyl isopropyl acetal and chloroacetaldehyde 5,5-dimethyl-2-cyclopentenyl isobutyl acetal;

[0094] Bromoacetaldehyde branched alkyl dimethyl-2-cyclopentenyl acetals, such as bromoacetaldehyde 2,3-dimethyl-2-cyclopentenyl isopropyl acetal, bromoacetaldehyde 2,3-dimethyl-2-cyclopentenyl isobutyl acetal, bromoacetaldehyde 5,5-dimethyl-2-cyclopentenyl isopropyl acetal and bromoacetaldehyde 5,5-dimethyl-2-cyclopentenyl isobutyl acetal;

[0095] Iodoacetaldehyde branched alkyl dimethyl-2-cyclopentenyl acetals, such as iodoacetaldehyde 2,3-dimethyl-2-cyclopentenyl isopropyl acetal, iodoacetaldehyde 2,3-dimethyl-2-cyclopentenyl isobutyl acetal, iodoacetaldehyde 5,5-dimethyl-2-cyclopentenyl isopropyl acetal and iodoacetaldehyde 5,5-dimethyl-2-cyclopentenyl isobutyl acetal;

[0096] Chloroacetaldehyde straight-chain alkyl trimethyl-2-cyclopentenyl acetals, such as chloroacetaldehyde methyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde n-propyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde methyl 2,3,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde ethyl 2,3,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde n-propyl 2,3,4-trimethyl-2-cyclopentenyl acetal, and chloroacetaldehyde n-butyl 2,3,4-trimethyl-2-cyclopentenyl acetal;

[0097] Bromoacetaldehyde straight-chain alkyl trimethyl-2-cyclopentenyl acetals, such as bromoacetaldehyde methyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde n-propyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde methyl 2,3,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde ethyl 2,3,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde n-propyl 2,3,4-trimethyl-2-cyclopentenyl acetal, and bromoacetaldehyde n-butyl 2,3,4-trimethyl-2-cyclopentenyl acetal;

[0098] Iodoacetaldehyde straight-chain alkyl trimethyl-2-cyclopentenyl acetals, such as iodoacetaldehyde methyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde n-propyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde methyl 2,3,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde ethyl 2,3,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde n-propyl 2,3,4-trimethyl-2-cyclopentenyl acetal, and iodoacetaldehyde n-butyl 2,3,4-trimethyl-2-cyclopentenyl acetal;

[0099] Chloroacetaldehyde branched alkyl trimethyl-2-cyclopentenyl acetals, such as chloroacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde isobutyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde isopropyl 2,3,4-trimethyl-2-cyclopentenyl acetal and chloroacetaldehyde isobutyl 2,3,4-trimethyl-2-cyclopentenyl acetal;

[0100] Bromoacetaldehyde branched alkyl trimethyl-2-cyclopentenyl acetals, such as bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde isobutyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde isopropyl 2,3,4-trimethyl-2-cyclopentenyl acetal, and bromoacetaldehyde isobutyl 2,3,4-trimethyl-2-cyclopentenyl acetal; and

[0101] Iodoacetaldehyde branched alkyl trimethyl-2-cyclopentenyl acetals, such as iodoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde isobutyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde isopropyl 2,3,4-trimethyl-2-cyclopentenyl acetal, and iodoacetaldehyde isobutyl 2,3,4-trimethyl-2-cyclopentenyl acetal.

[0102] In addition, the haloacetal alkyl 2-cyclopentenyl acetal compound (1) can be its enantiomers, diastereomers, and mixtures of the same or different amounts of such stereoisomers.

[0103] Next, the method for preparing the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) will be described below.

[0104] The alkyl 2-cyclopentenyl acetal compound (1) can be prepared, for example, by halogenating an alkyl vinyl ether compound of the following general formula (4) with a halogenating agent to form a halide, and then subjecting the halide obtained therefrom to a substitution reaction with a 2-cyclopenten-1-ol compound of the following general formula (5), as shown in the following reaction formula (see Examples 1-1 to 1-7 below).

[0105]

[0106] The method for preparing haloacetal alkyl 2-cyclopentenyl acetals (1) will be described in further detail below.

[0107] The starting material, alkyl vinyl ether compound (4), will be described below.

[0108] R in general formula (4) is defined as in general formula (1).

[0109] Examples of alkyl vinyl ether compounds (4) include straight-chain alkyl vinyl ethers such as methyl vinyl ether, ethyl vinyl ether, n-propyl vinyl ether and n-butyl vinyl ether; and branched-chain alkyl vinyl ethers such as isopropyl vinyl ether and isobutyl vinyl ether.

[0110] Alkyl vinyl ether compounds (4) can be purchased on the market or prepared at home.

[0111] Halogenation of alkyl vinyl ether compounds (4) can be carried out using halogenating agents, and can be carried out by heating or cooling if necessary.

[0112] Examples of halogenating agents used in halogenation include chlorinating agents such as chlorine, thioyl chloride, N-chlorosuccinimide, dichloroiodobenzene, tetrabutyliodotetrachloride, titanium tetrachloride (IV), and copper chloride (II); brominating agents such as bromine, N-bromosuccinimide, N-bromoacetamide, 1,3-dibromo-5,5-dimethylhydantoin, tetrabutyltribromide, phenyltrimethyltribromide, dibromoiodobenzene, copper bromide (II), cuprous bromide (I), magnesium bromide (II), and aluminum bromide; iodizing agents such as iodine, N-iodosuccinimide, and 1,3-diiodo-5,5-dimethylhydantoin; and chloroiodizing agents such as iodine monochloride and potassium tetrachloroiodate. Brominating agents and iodizing agents are preferred. From the perspective of reactivity and / or yield, bromine and N-bromosuccinimide in the brominating agent and iodine and N-iodosuccinimide in the iodizing agent are preferred.

[0113] The amount of halogenating agent used in halogenation varies depending on the structure and / or reactivity of the alkyl vinyl ether compound (4) and / or the halogenating agent. From the perspective of yield and / or the generation of impurities as byproducts, the amount is preferably 0.2 mol to 5.0 mol, more preferably 0.5 mol to 2.0 mol, relative to each mol of alkyl vinyl ether compound (4).

[0114] The solvent used in halogenation can be any solvent that does not adversely affect the halogenation process. Examples of solvents used in halogenation include halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; ether solvents such as diethyl ether, n-butyl ether, tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; hydrocarbon solvents such as hexane and heptane; and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and hexamethylphosphoric triamine. From a reactivity perspective, halogen-based solvents, ether solvents, and aprotic polar solvents are preferred.

[0115] If necessary, the solvent may be used alone or in combination thereof, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the alkyl vinyl ether compound (4) and / or the halogenating agent.

[0116] While taking into account the type and / or reactivity of the alkyl vinyl ether compound (4) and / or the halogenating agent, the amount of solvent used in halogenation may optionally be determined, for example, from the perspective of yield and / or the generation of impurities as byproducts, the amount of solvent is preferably 50 g to 10,000 g, more preferably 500 g to 8,000 g, relative to each mol of the alkyl vinyl ether compound (4).

[0117] While taking into account the reactivity of the alkyl vinyl ether compound (4) and / or the formation of halogenating agents, the reaction temperature of halogenation may optionally be determined, for example, preferably from -60°C to 150°C, more preferably from -20°C to 50°C, from the perspective of reactivity and / or the formation of halogenating agents.

[0118] Preferably, the halogenation reaction time is optimized based on the reactivity of the alkyl vinyl ether compound (4) and / or the halogenating agent by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the alkyl vinyl ether compound (4) and / or the halogenating agent. For example, from the perspective of yield and / or impurity formation, the halogenation reaction time is preferably 0.5 hours to 168 hours, more preferably 0.5 hours to 24 hours, and even more preferably 0.5 hours to 6 hours.

[0119] Halides prepared by halogenating alkyl vinyl ether compounds (4) with a halogenating agent are considered to be alkyl 1,2-dihaloethyl ethers having the following general formula (7). The halides may be isolated and / or purified after halogenation and then used in subsequent steps, or used as is in the reaction mixture in subsequent steps without isolation and / or purification after halogenation.

[0120]

[0121] In general formula (7), R is defined as in general formula (4), and Y represents halogen atoms independently of each other. Examples of halogen atoms include chlorine, bromine, and iodine atoms. From the perspective of yield and / or reactivity, bromine or iodine atoms are preferred. Y can be the same or different from each other independently. For example, when the halogenating agent is a chloroiodizing agent (such as iodine monochloride or potassium tetrachloroiodate), Y can be different from each other independently.

[0122] Next, the 2-cyclopenten-1-ol compound (5) will be described below.

[0123] X1 to X7 in general formula (5) are as defined in general formula (1). When the haloacetal alkyl 2-cyclopentenyl acetal compound (1) is prepared from 2-cyclopenten-1-ol compound (5), each of X1 to X7 in general formula (1) is a hydrogen atom or methyl group as defined in general formula (5).

[0124] Examples of 2-cyclopenten-1-ol compounds (5) include monomethyl-2-cyclopenten-1-ol, such as 3-methyl-2-cyclopenten-1-ol and 5-methyl-2-cyclopenten-1-ol; dimethyl-2-cyclopenten-1-ol, such as 2,3-dimethyl-2-cyclopenten-1-ol and 5,5-dimethyl-2-cyclopenten-1-ol; and trimethyl-2-cyclopenten-1-ol, such as 3,4,4-trimethyl-2-cyclopenten-1-ol and 2,3,4-trimethyl-2-cyclopenten-1-ol.

[0125] 2-Cyclopenten-1-ol compound (5) can be purchased on the market or prepared at home.

[0126] In the substitution reaction, the halogen atom (i.e., secondary Y) in the halide is replaced by 2-cyclopenten-1-ol compound (5) to form haloacetal alkyl 2-cyclopentenyl acetal compound (1).

[0127] From the perspective of yield and / or byproduct formation and / or economy, the amount of 2-cyclopenten-1-ol compound (5) used is preferably 0.2 mol to 5.0 mol, more preferably 0.5 mol to 2.0 mol, relative to each mol of alkyl vinyl ether compound (4).

[0128] If desired, the substitution reaction can be carried out by heating or cooling. Considering the reactivity of the 2-cyclopenten-1-ol compound (5) and the halide and / or the formation of impurities as byproducts, the substitution reaction can be carried out in the presence of a base.

[0129] Examples of bases include amines such as triethylamine, diisopropylethylamine, pyridine, N,N-dimethylaminopyridine, and N,N-dimethylaniline; organometallic compounds such as n-butyllithium, methyllithium, and phenyllithium; metal amines such as diisopropylaminolithium, hexamethyldisilaminolithium, hexamethyldisilaminosodium, and dicyclohexylaminolithium; metal hydroxides such as sodium hydroxide and potassium hydroxide; and metal carbonates such as potassium carbonate, sodium carbonate, and sodium bicarbonate.

[0130] If necessary, the base may be used alone or in combination with it, and may be optionally determined while taking into account the reactivity and / or impurity formation of the 2-cyclopenten-1-ol compound (5) and / or halides.

[0131] The amount of base used may be optionally determined while taking into account the reactivity and / or impurity formation of the 2-cyclopenten-1-ol compound (5) and / or halides. For example, from the perspective of reactivity and / or economy, the amount is preferably 0.5 mol to 5.0 mol, more preferably 0.8 mol to 2.0 mol, relative to each mol of the 2-cyclopenten-1-ol compound (5).

[0132] The solvent used in a substitution reaction can be any solvent that does not adversely affect the substitution reaction. Examples of solvents used in substitution reactions include halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; hydrocarbon solvents such as hexane, heptane, benzene, and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; nitrile solvents such as acetonitrile; ketone solvents such as acetone, methyl ethyl ketone, and diisobutyl ketone; ester solvents such as ethyl acetate and butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and hexamethylphosphoric triamine. From the perspective of reactivity and / or yield, halogen-based solvents, ether solvents, and aprotic polar solvents are preferred.

[0133] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the 2-cyclopenten-1-ol compound (5) and / or the halide.

[0134] The solvent used in the substitution reaction can be the same solvent that was used in the halogenation as before. Any solvent of the same type as that used in the halogenation or any solvent different from that used in the halogenation can be added to the substitution reaction system to increase reactivity and / or adjust the concentration.

[0135] The amount of solvent used in the substitution reaction may be optionally determined while taking into account the reactivity and / or impurity formation of the 2-cyclopenten-1-ol compound (5) and / or halides. For example, from the perspective of reactivity and / or the formation of impurities as byproducts, the amount is preferably 50 g to 10,000 g, more preferably 500 g to 8,000 g, relative to each mol of the 2-cyclopenten-1-ol compound (5).

[0136] While taking into account the reactivity and / or impurity formation of the 2-cyclopenten-1-ol compound (5) and / or halides, the reaction temperature of the substitution reaction may optionally be determined, for example, preferably -60°C to 150°C, more preferably -20°C to 50°C, from the perspective of reactivity and / or impurity formation.

[0137] Preferably, the reaction time of the substitution reaction is optimized based on the reactivity of the 2-cyclopenten-1-ol compound (5) and / or the halide by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the 2-cyclopenten-1-ol compound (5) and / or the halide. For example, from the perspective of yield and / or impurity formation, the reaction time of the substitution reaction is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 6 hours.

[0138] The haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) formed in the substitution reaction can be appropriately separated and / or purified by any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. Vacuum distillation is preferred from an industrial economic point of view. When the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) formed in the substitution reaction has sufficient purity, the crude product containing the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) can be used as is in subsequent steps without purification.

[0139] B. Next, a method for preparing (2-cyclopentenyl)acetic acid ester compounds of the following general formula (2) will be described below.

[0140] (2-Cyclopentenyl)acetate compound (2) was prepared as follows: haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) was subjected to dehydrohalogenation (-HY) in the presence of a base, followed by a rearrangement reaction as shown in the following reaction formula (see Examples 2-1 to 2-9 below).

[0141]

[0142] The starting material, a haloacetal alkyl 2-cyclopentenyl acetal compound (1), is as described above. R in general formula (1) is as defined above, and from a reactivity perspective, a straight-chain alkyl group having 1 to 4 carbon atoms is preferred. From a reactivity and / or usability perspective, a straight-chain alkyl group having 1 to 3 carbon atoms, i.e., a methyl group, an ethyl group, and a n-propyl group, is more preferred.

[0143] Next, the (2-cyclopentenyl)acetic acid compound (2) formed in the rearrangement reaction will be described below.

[0144] R and X1 to X7 in general formula (2) are as defined in general formula (1). When the (2-cyclopentenyl)acetate compound (2) is prepared from the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1), each of X1 to X7 in general formula (2) is a hydrogen atom or a methyl group as defined in general formula (1).

[0145] Examples of (2-cyclopentenyl)acetic acid ester compounds (2) include straight-chain alkyl (monomethyl-2-cyclopentenyl)acetic acid esters, such as methyl (1-methyl-2-cyclopentenyl)acetate, ethyl (1-methyl-2-cyclopentenyl)acetate, n-propyl (1-methyl-2-cyclopentenyl)acetate, n-butyl (1-methyl-2-cyclopentenyl)acetate, methyl (4-methyl-2-cyclopentenyl)acetate, ethyl (4-methyl-2-cyclopentenyl)acetate, n-propyl (4-methyl-2-cyclopentenyl)acetate, and n-butyl (4-methyl-2-cyclopentenyl)acetate; branched-chain alkyl (monomethyl-2-cyclopentenyl)acetic acid esters, such as isopropyl (1-methyl-2-cyclopentenyl)acetate. Esters, (1-methyl-2-cyclopentenyl)isobutyl acetate, (4-methyl-2-cyclopentenyl)isopropyl acetate and (4-methyl-2-cyclopentenyl)isobutyl acetate; linear alkyl (dimethyl-2-cyclopentenyl) acetate esters, such as (1,2-dimethyl-2-cyclopentenyl)methyl acetate, (1,2-dimethyl-2-cyclopentenyl)ethyl acetate, (1,2-dimethyl-2-cyclopentenyl)n-propyl acetate, (1,2-dimethyl-2-cyclopentenyl)n-butyl acetate, (4,4-dimethyl-2-cyclopentenyl)methyl acetate, (4,4-dimethyl-2-cyclopentenyl)ethyl acetate, (4,4-dimethyl-2-cyclopentenyl)n-propyl acetate and (4,4-Dimethyl-2-cyclopentenyl)acetic acid n-butyl ester; branched alkyl (dimethyl-2-cyclopentenyl)acetic acid esters, such as (1,2-dimethyl-2-cyclopentenyl)acetic acid isopropyl ester, (1,2-dimethyl-2-cyclopentenyl)acetic acid isobutyl ester, (4,4-dimethyl-2-cyclopentenyl)acetic acid isopropyl ester and (4,4-dimethyl-2-cyclopentenyl)acetic acid isobutyl ester; straight-chain alkyl (trimethyl-2-cyclopentenyl)acetic acid esters, such as (1,5,5-trimethyl-2-cyclopentenyl)acetic acid methyl ester, (1,5,5-trimethyl-2-cyclopentenyl)acetic acid ethyl ester, (1,5,5-trimethyl-2-cyclopentenyl)acetic acid n-propyl ester, (1,5,5- (1,2,5-Trimethyl-2-cyclopentenyl)butyrate, (1,2,5-trimethyl-2-cyclopentenyl)methyl acetate, (1,2,5-trimethyl-2-cyclopentenyl)ethyl acetate, (1,2,5-trimethyl-2-cyclopentenyl)propyl acetate and (1,2,5-trimethyl-2-cyclopentenyl)butyrate; and branched alkyl (trimethyl-2-cyclopentenyl) acetate esters, such as (1,5,5-trimethyl-2-cyclopentenyl)isopropyl acetate, (1,5,5-trimethyl-2-cyclopentenyl)isobutyl acetate, (1,2,5-trimethyl-2-cyclopentenyl)isopropyl acetate and (1,2,5-trimethyl-2-cyclopentenyl)isobutyl acetate.

[0146] When the (2-cyclopentenyl)acetic acid compound (2) of general formula (2) has one or more asymmetric carbon atoms, the (2-cyclopentenyl)acetic acid compound (2) includes its enantiomers, diastereomers and mixtures of the same or different amounts of such stereoisomers.

[0147] Dehydrohalogenation reactions can be carried out in the presence of a base, and if necessary, by heating or cooling.

[0148] Examples of bases used in dehydrohalogenation reactions include metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, potassium methoxide, potassium ethoxide, and potassium tert-butoxide; metal hydroxides such as sodium hydroxide, lithium hydroxide, and potassium hydroxide; organometallic reagents such as methyllithium, ethyllithium, n-butyllithium, and methylmagnesium chloride; metal amines such as diisopropylaminolithium, hexamethyldisilaminolithium, hexamethyldisilaminosodium, and dicyclohexylaminolithium; and organonitrogen compounds such as triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, pyrrolidine, piperidine, trimethylpyridine, dimethylpyridine, morpholine, piperazine, 1,8-diazaheterocyclic [5.4.0]undec-7-ene, and 1,5-diazaheterocyclic [4.3.0]non-5-ene. Metal alkoxides are preferred from the perspective of reactivity and / or impurity formation.

[0149] If necessary, the base may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the haloacetal alkyl 2-cyclopentenyl acetal compound (1).

[0150] The amount of base used may vary depending on the structure and / or reactivity of the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1). For example, from the perspective of yield and / or impurity formation, the amount is preferably 0.2 mol to 5.0 mol, more preferably 0.5 mol to 2.0 mol, relative to each mol of haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1).

[0151] The solvent used in a dehydrohalogenation reaction can be any solvent that does not adversely affect the dehydrohalogenation reaction. Examples of solvents used in dehydrohalogenation reactions include alcohol solvents such as methanol, ethanol, isopropanol, and tert-butanol; ether solvents such as diethyl ether, n-butyl ether, tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; hydrocarbon solvents such as hexane, heptane, benzene, toluene, and xylene; aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolinone, dimethyl sulfoxide, and hexamethylphosphoric triamine; and nitrile solvents such as acetonitrile. From a reactivity perspective, ether solvents and aprotic polar solvents are preferred.

[0152] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the alkyl 2-cyclopentenyl acetal compound (1).

[0153] The amount of solvent used may be optionally determined while taking into account the reactivity and / or solubility of the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1), for example, preferably 30 g to 10,000 g, more preferably 100 g to 5,000 g, relative to each mol of the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1), from the perspective of reactivity and / or economy.

[0154] While taking into account the reactivity and / or impurity formation of the alkyl 2-cyclopentenyl acetal compound (1), the reaction temperature of the dehydrohalogenation reaction may optionally be determined, for example, from the perspective of reactivity and / or impurity formation, preferably from -60°C to 150°C, more preferably from -20°C to 80°C.

[0155] Preferably, the reaction time of the dehydrohalogenation reaction is optimized based on the reactivity of the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) as the substrate. For example, from the perspective of yield and / or impurity formation, the reaction time of the dehydrohalogenation reaction is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 12 hours.

[0156] During the dehydrohalogenation reaction, the alkyl 2-cyclopentenyl ketal compound of the following general formula (6) is considered to be formed in the reaction system as a product of the dehydrohalogenation reaction.

[0157]

[0158] R and X1 to X7 in general formula (6) are as defined in general formula (1). When the alkyl 2-cyclopentenyl ketone acetal compound (6) is prepared from the haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1), each of X1 to X7 in general formula (6) is a hydrogen atom or a methyl group as defined in general formula (1).

[0159] The products of dehydrohalogenation reactions can be separated and / or purified using any purification method commonly used in organic synthesis (such as vacuum distillation and / or various chromatographic methods) and then used in subsequent rearrangement reactions. When the products of dehydrohalogenation reactions are difficult to separate and / or purify due to their properties, the products are preferably used as is in subsequent rearrangement reactions.

[0160] Next, in the rearrangement reaction, (2-cyclopentenyl)acetate compound (2) is prepared from the product of the dehydrohalogenation reaction via the [3,3]-σ migration rearrangement, as shown in the following reaction formula. When X2 in (2-cyclopentenyl)acetate compound (2) is a methyl group, the carbon atom attached to the alkoxycarbonyl methyl group becomes a quaternary group, resulting in greater steric hindrance of (2-cyclopentenyl)acetate compound (2) and making it difficult to prepare (2-cyclopentenyl)acetate compound (2) using common anionic species. Therefore, the preparation method using the [3,3]-σ migration rearrangement is considered to be effective among the methods for preparing (2-cyclopentenyl)acetate compound (2).

[0161]

[0162] The rearrangement reaction can be carried out in a solvent or not, and can be carried out by heating or cooling if necessary.

[0163] The solvent used in a rearrangement reaction can be any solvent that does not adversely affect the rearrangement reaction. Examples of solvents used in rearrangement reactions include alcohol solvents such as methanol, ethanol, isopropanol, and tert-butanol; ether solvents such as diethyl ether, n-butyl ether, di-tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; hydrocarbon solvents such as hexane, heptane, benzene, toluene, and xylene; aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolinone, dimethyl sulfoxide, and hexamethylphosphoric triamine; and nitrile solvents such as acetonitrile. From a reactivity perspective, ether solvents and aprotic polar solvents are preferred.

[0164] If necessary, the solvent may be used alone or in combination, and may be optionally determined while taking into account the type and / or reactivity of the dehydrohalogenation reaction products.

[0165] When the products of the dehydrohalogenation reaction are used in a subsequent rearrangement reaction without separation and / or purification, the solvent used in the rearrangement reaction can be the same as the solvent used in the dehydrohalogenation reaction. Any additional solvent can be used in the rearrangement reaction system to adjust the reaction temperature and / or concentration.

[0166] The amount of solvent used in the rearrangement reaction can be optionally determined while taking into account the reactivity and / or solubility of the dehydrohalogenation reaction product (the substrate of the rearrangement reaction). For example, from the perspective of reactivity and / or economy, the amount of solvent used relative to each mol of haloacetaldehyde alkyl 2-cyclopentenyl acetal compound (1) or the product of the dehydrohalogenation reaction is preferably greater than 0 g to 10,000 g, more preferably 50 g to 3,000 g.

[0167] While taking into account the reactivity of the dehydrohalogenation reaction products and / or the formation of impurities, the reaction temperature of the rearrangement reaction can be optionally determined, for example, preferably from -60°C to 250°C, more preferably from 0°C to 150°C, from the perspective of reactivity and / or impurity formation.

[0168] Preferably, the reaction time of the rearrangement reaction is optimized based on the reactivity of the dehydrohalogenation reaction products by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the dehydrohalogenation reaction products. For example, from the perspective of yield and / or impurity formation, the reaction time of the rearrangement reaction is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 6 hours.

[0169] The (2-cyclopentenyl)acetate compound (2) formed in the rearrangement reaction can be appropriately separated and / or purified by any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. Vacuum distillation is preferred from an industrial economic point of view. When the (2-cyclopentenyl)acetate compound (2) formed in the rearrangement reaction has sufficient purity, the crude product containing the (2-cyclopentenyl)acetate compound (2) can be used as is in subsequent steps without purification.

[0170] C. The following describes a method for preparing (2-cyclopentenyl)acetic acid compounds of the following general formula (3).

[0171] (2-Cyclopentenyl)acetic acid compound (3) is prepared by hydrolyzing the (2-cyclopentenyl)acetic acid ester compound (2) obtained in part B, as shown in the following reaction formula (see Examples 3-1 to 3-5 below).

[0172]

[0173] The starting material (2-cyclopentenyl) acetate compound (2) is as described above.

[0174] Next, the (2-cyclopentenyl)acetic acid compound (3) that will be formed in the hydrolysis reaction will be described below.

[0175] X1 to X7 in general formula (3) are as defined in general formula (1). When (2-cyclopentenyl)acetic acid compound (3) is prepared from (2-cyclopentenyl)acetic acid ester compound (2), each of X1 to X7 in general formula (3) is a hydrogen atom or methyl group as defined in general formula (2).

[0176] Examples of (2-cyclopentenyl)acetic acid compounds (3) include (monomethyl-2-cyclopentenyl)acetic acid, such as (1-methyl-2-cyclopentenyl)acetic acid and (4-methyl-2-cyclopentenyl)acetic acid; (dimethyl-2-cyclopentenyl)acetic acid, such as (1,2-dimethyl-2-cyclopentenyl)acetic acid and (4,4-dimethyl-2-cyclopentenyl)acetic acid; and (trimethyl-2-cyclopentenyl)acetic acid, such as (1,5,5-trimethyl-2-cyclopentenyl)acetic acid and (1,2,5-trimethyl-2-cyclopentenyl)acetic acid.

[0177] When (2-cyclopentenyl)acetic acid compound (3) has one or more asymmetric carbons, (2-cyclopentenyl)acetic acid compound (3) can be its enantiomers, diastereomers, and mixtures of the same or different amounts of such stereoisomers.

[0178] Hydrolysis can be any known hydrolysis reaction, and can be carried out by heating or cooling if necessary.

[0179] For example, hydrolysis can be carried out under alkaline conditions in the presence of a base, under acidic conditions in the presence of an acid, or under neutral conditions in the presence of a salt or a silane halide.

[0180] Examples of bases used for hydrolysis under alkaline conditions include hydroxide salts such as sodium hydroxide, lithium hydroxide, potassium hydroxide, and barium hydroxide; carbonates or bicarbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate; and alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, potassium methoxide, potassium ethoxide, and potassium tert-butoxide.

[0181] If necessary, the base may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the (2-cyclopentenyl)acetic acid compound (2).

[0182] Examples of acids used for hydrolysis under acidic conditions include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and nitric acid; organic acids such as acetic acid, formic acid, oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; and Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, boron trifluoride, boron trichloride, boron tribromide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium methoxide (IV), titanium ethoxide (IV), and titanium isopropoxide (IV).

[0183] If necessary, the acid may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the (2-cyclopentenyl)acetic acid compound (2).

[0184] Examples of salts or silane halides used for hydrolysis under neutral conditions include salts such as lithium iodide, lithium bromide, sodium cyanide, potassium cyanide, lithium methanethiol, and sodium benzenethiolate; and silane halides such as trimethyliodosilane and trimethylbromosilane.

[0185] If necessary, the salt or halosilane may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the (2-cyclopentenyl)acetic acid ester compound (2).

[0186] From the perspective of yield and / or impurity formation, the hydrolysis reaction is preferably carried out under alkaline conditions, and more preferably in the presence of hydroxide salts, carbonates or bicarbonates.

[0187] The amount of base, acid, salt or halosilane used in the hydrolysis reaction can be set arbitrarily from a very low catalytic amount to a large excess, depending on the reactivity of the (2-cyclopentenyl)acetic acid compound (2). For example, from the perspective of reaction time and / or yield, it is preferably 0.1 mol to 50.0 mol, more preferably 0.5 mol to 10.0 mol, relative to each mol of (2-cyclopentenyl)acetic acid compound (2).

[0188] The solvent used in the hydrolysis reaction can be any solvent that does not adversely affect the hydrolysis reaction. Examples of solvents used in hydrolysis reactions include water; alcohol solvents, such as methanol, ethanol, isopropanol, and tert-butanol; ether solvents, such as diethyl ether, n-butyl ether, tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; hydrocarbon solvents, such as hexane, heptane, benzene, toluene, and xylene; aprotic polar solvents, such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolinone, dimethyl sulfoxide, and hexamethylphosphoric triamine; and nitrile solvents, such as acetonitrile. From a reactivity perspective, alcohol solvents and ether solvents are preferred.

[0189] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity of the (2-cyclopentenyl)acetic acid compound (2).

[0190] The amount of solvent used may be optionally determined while taking into account the reactivity and / or solubility of the (2-cyclopentenyl)acetic acid compound (2), for example, preferably 30 g to 20,000 g, more preferably 50 g to 8,000 g, relative to each mol of the (2-cyclopentenyl)acetic acid compound (2), from the perspective of reactivity and / or economy.

[0191] While taking into account the reactivity and / or impurity formation of (2-cyclopentenyl)acetic acid compound (2), the reaction temperature of the hydrolysis reaction may optionally be determined, for example, preferably from -60°C to 250°C, more preferably from 0°C to 100°C, from the perspective of reactivity and / or impurity formation.

[0192] Preferably, the reaction time of the hydrolysis reaction is optimized based on the reactivity of the (2-cyclopentenyl)acetate compound (2) by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the (2-cyclopentenyl)acetate compound (2) as the substrate. For example, considering the yield and / or impurity formation, the reaction time of the water reaction is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 12 hours.

[0193] The (2-cyclopentenyl)acetic acid compound (3) formed in the hydrolysis reaction can be treated by dissolving it under alkaline conditions to form a carboxylate in the aqueous layer, extracting the aqueous layer containing the carboxylate, separating the organic layer, acidifying the resulting aqueous layer and re-extracting the aqueous layer with an organic solvent.

[0194] The (2-cyclopentenyl)acetic acid compound (3) formed in the hydrolysis reaction can be separated and / or purified by any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. From an industrial economic point of view, vacuum distillation is preferred. When the target compound (2-cyclopentenyl)acetic acid compound (3) has sufficient purity, the crude product containing (2-cyclopentenyl)acetic acid compound (3) can be used directly in subsequent steps without purification.

[0195] Therefore, by subjecting the alkyl 2-cyclopentenyl acetal compound (1) to dehydrohalogenation in the presence of a base and then to rearrangement, (2-cyclopentenyl)acetic acid compounds (2) and (2-cyclopentenyl)acetic acid compounds (3) can be prepared in an industrially readily applicable reaction temperature range without the use of flammable and industrially expensive starting materials.

[0196] Example

[0197] The present invention will be described with reference to the following embodiments and comparative examples. It should be understood that the present invention is not limited to or not construed as being limited by these embodiments.

[0198] Unless otherwise specified, the term "purity" as used herein refers to the percentage of area determined by gas chromatography (hereinafter also referred to as "GC"). The term "product ratio" refers to the relative ratio of the percentage of area determined by GC.

[0199] The term "yield" is calculated as a percentage of the area determined by GC.

[0200] The yield was calculated using the following equation, taking into account the purity (%GC) of the starting materials and the product.

[0201] Yield (%) = {[(mass of product × % GC) / molecular weight of product] ÷ [(mass of starting material × % GC) / molecular weight of starting material]} × 100

[0202] GC conditions are as follows:

[0203] GC conditions used to determine “purity” and “product ratio”: GC: GC-2010 capillary gas chromatograph (Shimadzu Corporation); column: DB-5, 0.25μm×0.25mmφ×30m; carrier gas: He (1.55mL / min); detector: FID; column temperature: 60℃, hold for 3 minutes, increase at 10℃ / min, up to 230℃.

[0204] As used in this article, H represents a hydrogen atom, Me represents a methyl group, and Et represents an ethyl group. n Bu represents the n-butyl group. i Pr represents the isopropyl group, and Br represents the bromine atom. In the following reaction formulas, the descriptions of X1 to X7 of compound (1) are omitted.

[0205] Example 1

[0206] The following Examples 1-1 to 1-7 describe a method for preparing alkyl 2-cyclopentenyl acetal compounds (1) of haloacetaldehyde, as shown in the following reaction formula.

[0207]

[0208] Example 1-1

[0209] Preparation of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br)

[0210]

[0211] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, bromine (Br2) (26.36 g: 0.165 mol) and dichloromethane (CH2Cl2) (750.0 g) were added to the reactor, and the liquid temperature was lowered to -5°C to 0°C. Ethyl vinyl ether (4:R=Et) (12.98 g: 0.180 mol) was added dropwise over 90 minutes while maintaining the liquid temperature at -5°C to 0°C. After the addition was complete, the reaction mixture was stirred at the liquid temperature at -5°C to 0°C for 30 minutes. After stirring was complete, diisopropylethylamine was added over 10 minutes while maintaining the liquid temperature at -5°C to 0°C. i Pr)2NEt)(23.27g:0.180mol). After the addition was complete, 3,4,4-trimethyl-2-cyclopenten-1-ol (5:X1,X5,X6,X7=H;X2,X3,X4=Me) (18.93g:0.150mol, purity 94.9%) was added dropwise over 1 hour at a liquid temperature of -10°C to 5°C. After the addition was complete, the reaction mixture was stirred at a liquid temperature of -5°C to 0°C for 1 hour, and then stirred at a liquid temperature of 20°C to 25°C for 3 hours.

[0212] After stirring, a 3.5 wt% sodium bicarbonate aqueous solution (500.0 g) was added to the reaction mixture to quench the reaction. After quenching, the reaction mixture was separated into an organic phase and an aqueous phase. The resulting organic phase was washed successively with water (300.0 g) and a 10.0 wt% sodium chloride aqueous solution (300.0 g). The solvent was removed from the washed organic phase under reduced pressure, and the crude product was then purified by vacuum distillation to obtain bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et;X1,X5,X6,X7=H;X2,X3,X4=Me;Y=Br) (36.84 g: 0.133 mol, yield 88.6%, purity 91.8%).

[0213] The following are the various spectral data of the bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et;X1,X5,X6,X7=H;X2,X3,X4=Me;Y=Br) prepared therefrom.

[0214] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ1.00(1.5H,s),1.00(1.5H,s),1.10(1.5H,s),1.11(1.5H,s),1.22(1.5H,t,J=6.9 Hz), 1.23 (1.5H, t, J = 7.1Hz), 1.66 (1.5H, t, J = 1.6Hz), 1.66 (1.5H, t, J = 1.5Hz), 1.75 (0.5H, q, J = 4.4Hz), 1. 77(0.5H,q,4.4Hz),2.02(0.5H,q,J=5.7Hz),2.05(0.5H,q,J=5.7Hz),3.32-3.37(m,2H),3.53-3.62(1H,m) ,3.63-3.73(1H,m),4.62-4.68(1H,m),4.71(0.5H,t,J=2.9Hz),4.73(0.5H,t,J=3.1Hz),5.35(1H,br)ppm. 13 C-NMR (126MHz, CDCl3): δ12.29,15.13,15.22,27.31,27.35,27.73,27.82,32.29,32.42,45.09,45. 16,47.12,47.99,61.34,61.89,79.95,80.02,100.53,101.00,123.24,123.58,153.88,153.93ppm.

[0215] Mass spectrometry EI (70eV): m / z 152,151,125,123,93,91,83,81,79,77,72,57,43,29.

[0216] Infrared absorption spectrum (D-ATR): ν (cm) -1 )583,683,829,892,1032,1055,1115,1190,1223,1338,1361,1376,1437,1465,1653,2866,2929,2956,3046.

[0217] Examples 1-2

[0218] Preparation of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br)

[0219]

[0220] Repeat the steps of Example 1-1, except that triethylamine (NEt3) (18.21 g: 0.180 mol) is used instead of diisopropylethylamine. i Using Pr)2NEt) as a base, the resulting product is bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me; Y=Br) (30.60 g: 0.110 mol, yield 73.3%, purity 89.2%).

[0221] The spectral data of the bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me; Y=Br) prepared therefrom are the same as those determined in Examples 1-1.

[0222] Examples 1-3

[0223] Preparation of bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R= i Pr; X1, X5, X6, X7=H; X2, X3, X4=Me; Y=Br)

[0224]

[0225] Repeat the steps of Example 1-1, except that isopropyl vinyl ether (4:R= i Pr (15.50 g: 0.180 mol) was used to replace ethyl vinyl ether (4: R = Et), thus yielding bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et). i Pr; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br)(41.19 g: 0.141 mol, yield 94.3%, purity 87.8%).

[0226] The following is the bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) prepared from this. i Various spectral data for Pr; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br).

[0227] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ0.97(1.5H,s),0.97(1.5H,s),1.05(1.5H,s),1.05(1.5H,s) ,1.10(3H,d,J=6.0Hz),1.12(3H,dd,J=6.3,3.0Hz),1.62-1.65(4H,m),1.97(0.5H,dd, J=13.2,7.0Hz),2.02(0.5H,dd,J=13.2,7.0Hz),3.35-3.41(2H,m),3.82-3.86(1H,m) ,4.62(1H,m),4.69(0.5H,t,J=5.1Hz),4.71(0.5H,t,J=5.1),5.35(1H,d,22.8Hz)ppm. 13 C-NMR (126MHz, CDCl3): δ11.97,12.02,22.14,22.35,23.02,23.06,26.97,27.57,27.58,34.00,34.04,44 .51,44.59,46.96,47.69,68.39,68.51,78.23,78.24,98.62,98.78,123.96,124.25,152.10,152.13ppm.

[0228] Mass spectrometry EI (70eV): m / z 168,167,151,125,110,109,93,91,77,58,43,27.

[0229] Infrared absorption spectrum (D-ATR): ν (cm) -1 )681,829,1026,1124,1171,1202,1337,1380,1421,1437,1466,2867,2929,2969,3045.

[0230] Examples 1-4

[0231] Preparation of bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R= n Bu; X1, X5, X6, X7=H; X2, X3, X4=Me; Y=Br)

[0232]

[0233] Repeat the steps of Example 1-1, except that n-butyl vinyl ether (4:R= nBu (18.03 g: 0.180 mol) replaces ethyl vinyl ether (4: R = Et), thus yielding bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = n Bu; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br)(34.62 g: 0.113 mol, yield 75.6%, purity 84.0%).

[0234] The following is the bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) prepared from this process. n Various spectral data for (Bu; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br).

[0235] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.88(3H,t,J=7.5Hz),0.97(3H,s),1.05(3H,s),1.34(2 H,sextd,J=7.5,2.4Hz),1.46-1.51(2H,m),1.63-1.66(4H,m),1.98(0.5H,q,J=6. 6Hz),2.01(0.5H,q,J=6.6Hz),3.39-3.47(3H,m),3.50-3.57(1H,m),4.60-4.62(1 H, m), 4.67 (1H, q, J = 5.6Hz), 5.33 (0.5H, t, J = 1.5Hz), 5.37 (0.5H, t, J = 1.5Hz) ppm. 13 C-NMR (126MHz, CDCl3): δ11.97,12.02,13.69,18.78,26.95,27.56,31.29,31.31,33.25,33.29,44.51 ,44.59,46.87,47.55,65.03,65.45,79.11,79.21,99.94,100.23,123.82,124.22,152.20,152.31ppm.

[0236] Mass spectrometry EI (70eV): m / z 181,179,151,125,109,93,91,77,57,41.

[0237] Infrared absorption spectrum (D-ATR): ν (cm) -1 )684,829,1036,1114,1187,1224,1338,1360,1377,1435,1465,1653,2869,2933,2957,3047.

[0238] Examples 1-5

[0239] Preparation of bromoacetaldehyde 2,3-dimethyl-2-cyclopentenylethyl acetal (1: R = Et; X3, X4, X5, X6, X7 = H; X1, X2 = Me; Y = Br)

[0240]

[0241] The steps of Example 1-1 were repeated, except that 2,3-dimethyl-2-cyclopenten-1-ol (5:X3,X4,X5,X6,X7=H;X1,X2=Me) (16.83 g: 0.150 mol, purity 93.6%) was used instead of 3,4,4-trimethyl-2-cyclopenten-1-ol (5:X1,X5,X6,X7=H;X2,X3,X4=Me) as the reaction substrate. Therefore, bromoacetaldehyde 2,3-dimethyl-2-cyclopentenylethyl acetal (1:R=Et;X3,X4,X5,X6,X7=H;X1,X2=Me;Y=Br) (33.79 g: 0.128 mol, yield 85.3%, purity 87.8%) was obtained.

[0242] The following are the various spectral data of bromoacetaldehyde 2,3-dimethyl-2-cyclopentenylethyl acetal (1:R=Et;X3,X4,X5,X6,X7=H;X1,X2=Me;Y=Br) prepared therefrom.

[0243] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.12(1.5H,t,J=7.2Hz),1.14(1.5H,t,J=6.9Hz),1.60-1.62(6H,m),1.63-1.70(1H,m),2.03-2.15(2H,m),2.3 0(1H,br),3.41-3.49(2H,m),3.51-3.65(2H,m),4.47(0.5H,br),4.55(0.5H,br),4.68(0.5H,t,J=5.4Hz),4.70(0.5H,t,J=5.4Hz)ppm. 13 C-NMR (126MHz, CDCl3): δ11.30,11.31,13.95,15.15,15.23,28.91,29.87,33.36,33.46,35 .07,35.18,60.78,61.32,85.30,86.78,99.53,101.37,130.83,131.33,135.27,135.81ppm.

[0244] Mass spectrometry EI (70eV): m / z 152,149,137,123,121,111,95,94,79,72,55,42,29.

[0245] Infrared absorption spectrum (D-ATR): ν (cm) -1 )683,1031,1056,1113,1185,1336,1381,1422,1442,2849,2913,2974.

[0246] Examples 1-6

[0247] Preparation of bromoacetaldehyde 5,5-dimethyl-2-cyclopentenylethyl acetal (1: R = Et; X1, X2, X3, X4, X7 = H; X5, X6 = Me; Y = Br)

[0248]

[0249] Repeat the steps of Example 1-1, except that 5,5-dimethyl-2-cyclopenten-1-ol (5:X1, X2, X3, X4, X7 = H; X5, X6 = Me) (16.83 g: 0.150 mol, purity 82.3%) is used instead of 3,4,4-trimethyl-2-cyclopenten-1-ol (5:X1, X5, X6, X7 = H);

[0250] Using X2, X3, X4 = Me as the reaction substrate, the resulting product was bromoacetaldehyde 5,5-dimethyl-2-cyclopentenylethyl acetal (1: R = Et; X1, X2, X3, X4, X7 = H; X5, X6 = Me; Y = Br) (36.28 g: 0.138 mol, yield 91.9%, purity 80.8%).

[0251] The following are the various spectral data of bromoacetaldehyde 5,5-dimethyl-2-cyclopentenylethyl acetal (1:R=Et;X1,X2,X3,X4,X7=H;X5,X6=Me;Y=Br) prepared therefrom.

[0252] Nuclear magnetic resonance spectroscopy: 1H-NMR (600MHz, CDCl3): δ1.07 (1.5H, s), 1.08 (1.5H, s), 1.24 (1.5H, t, J = 5.1Hz), 1.25 (1.5H, t,J=7.2Hz),2.04-2.06(0.5H,m),2.07-2.09(0.5H,m),2.23(0.5H,quin,J=2.4Hz),2.26(0. 5H,quin,J=1.8Hz),3.33-3.40(2H,m),3.56-3.74(2H,m),4.17(1H,d,J=12.6Hz),4.74-4.77 (1H,m),5.72(0.5H,dd,J=6.3,4.2Hz),5.75(0.5H,dd,J=5.8,3.9Hz),5.89-5.92(1H,m)ppm. 13 C-NMR (150MHz, CDCl3): δ15.36,23.24,23.33,28.71,29.02,32.11,32.49,41.96,42.16,46. 78,46.82,61.18,62.01,88.54,90.52,101.02,102.44,130.12,131.02,134.37,134.85ppm.

[0253] Mass spectrometry EI (70eV): m / z 153,151,125,123,81,79,55,41.

[0254] Infrared absorption spectrum (D-ATR): ν (cm) -1 )684,1031,1056,1125,1190,1346,1364,1422,1444,1467,2870,2901,2929,2958,2975.

[0255] Examples 1-7

[0256] Preparation of bromoacetaldehyde ethyl 3-methyl-2-cyclopentenyl acetal (1: R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me; Y = Br)

[0257]

[0258] Repeat the steps of Example 1-1, except that 3-methyl-2-cyclopenten-1-ol (5:X1, X3, X4, X5, X6, X7=H; X2=Me) (14.72g: 0.150mol, purity 93.6%) is used instead of 3,4,4-trimethyl-2-cyclopenten-1-ol (5:X1, X5, X6, X7=H);

[0259] Using X2, X3, X4 = Me as the reaction substrate, the resulting product is bromoacetaldehyde ethyl 3-methyl-2-cyclopentenyl acetal (1: R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me; Y = Br) (27.28 g: 0.110 mol, yield 73.3%, purity 89.9%).

[0260] The following are the various spectral data of the bromoacetaldehyde ethyl 3-methyl-2-cyclopentenyl acetal (1: R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me; Y = Br) prepared therefrom.

[0261] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.12(1.5H,t,6.9Hz),1.12(1.5H,t,7.2Hz),1.70-1.77(4H,m),2.70-2.13(1H,br m),2.13-2.22(1H,m),2.28-2.45(1H,br m),3.39-3.46(2H,m),3.48-3.53(1H,m),3.56-3.63(1H,m),4.68(0.5H,t,J=4.8Hz),4.69(0.5H,t,J=4.8Hz),4.72(1H,br m),5.42(0.5H,br t,J=1.8Hz),5.46(0.5H,br (t,J=1.8Hz)ppm. 13 C-NMR (126MHz, CDCl3): δ15.13,15.16,16.51,16.55,30.88,31.36,33.39,34.55 ,34.71,61.05,82.41,82.52,99.87,100.14125.28,125.63,145.13,145.18ppm.

[0262] Mass spectrometry EI (70eV): m / z 153, 151, 125, 123, 81.

[0263] Infrared absorption spectrum (D-ATR): ν (cm) -1 )681,826,996,1029,1111,1154,1190,1342,1378,1444,1658,2913,2932,2974.

[0264] Example 2

[0265] Examples 2-1 to 2-9 below describe a method for preparing (2-cyclopentenyl)acetic acid compound (2), as shown in the following reaction formula:

[0266]

[0267] Example 2-1

[0268] Preparation of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0269]

[0270] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me; Y=Br) (27.72 g: 0.100 mol, purity 92.0%) and N,N-dimethylformamide (DMF) (280.0 g) obtained according to Example 1-1 were added to the reactor, and the mixture was then cooled to a liquid temperature of 0°C to 5°C. Potassium tert-butoxide (t-BuOK) (12.34 g: 0.110 mol) was added over 30 minutes to the mixture, which was maintained at a liquid temperature of 0°C to 5°C. After the addition was complete, the reaction was maintained at a liquid temperature of 20°C to 25°C for 4 hours.

[0271] After the reaction, the reaction mixture was heated to 100°C and stirred for 5 hours. After stirring, the reaction mixture was cooled to 0°C to 5°C, and water (250.0 g) was added to the reactor to quench the reaction. Diethyl ether (300.0 g) was further added to the reactor to extract and separate the mixture into an organic layer and an aqueous layer. The organic layer was washed with a 10% by weight aqueous solution of sodium chloride (300.0 g). The solvent was removed from the washed organic layer under reduced pressure, and the crude product was then purified by silica gel column chromatography to obtain ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) (9.76 g: 0.050 mol, yield 49.7%, purity 82.2%).

[0272] The following are the various spectral data of the (1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et;X1,X5,X6,X7=H;X2,X3,X4=Me) prepared therefrom.

[0273] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ0.92(3H,s),0.96(3H,s),0.96(3H,s),1.25(3H,t,J=7.3Hz), 2.09(1H,dt,J=15.7,2.1Hz), 2.16(1H,dt,J=16.1, 2.2Hz), 2.18(1H,d,J=13.4Hz), 2.31(1H,d,J=13.4Hz), 4.11(2H,q,J=7.1Hz), 5.62(1H,dt,J=5.7,2.4Hz), 5.77(1H,dt,J=5.7,1.9Hz)ppm. 13 C-NMR (126MHz, CDCl3): δ14.27,19.79,23.95,24.47,40.78,44.04,46.64,49.81,59.97,127.77,138.79,173.07ppm.

[0274] Mass spectrometry EI (70 eV): m / z 196 (M) + ),181,167,150,135,122,109,108,107,93,91,81,79,77,67,55,41,28.

[0275] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,742,956,1034,1131,1187,1213,1294,1336,1367,1448,1463,1734,2843,2872,2968,2052.

[0276] Example 2-2

[0277] Preparation of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0278] The steps of Example 2-1 were repeated, except that after completing the reaction of Example 2-1, the reaction mixture was heated to 140°C instead of 100°C and stirred for 8 hours instead of 5 hours, thus obtaining ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2:R=Et;X1,X5,X6,X7=H;X2,X3,X4=Me) (9.38g:0.048mol, yield 47.8%, purity 80.0%).

[0279] The spectral data of the (1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) prepared therefrom are the same as those determined in Example 2-1.

[0280] Example 2-3

[0281] Preparation of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0282]

[0283] The steps of Example 2-1 were repeated, except that sodium tert-butoxide (t-BuONa) (10.57 g: 0.110 mol) was used instead of potassium tert-butoxide (t-BuOK) used as the base in Example 2-1. Thus, ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) was obtained (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) (8.62 g: 0.044 mol, yield 43.9%, purity 83.7%).

[0284] The spectral data of the (1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) prepared therefrom are the same as those determined in Example 2-1.

[0285] Examples 2-4

[0286] Preparation of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0287]

[0288] The steps of Example 2-1 were repeated, except that diethylene glycol dimethyl ether (Diglyme) (280.0) was used instead of N,N-dimethylformamide (DMF) used as a solvent in Example 2-1. Thus, (1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) (9.50 g: 0.048 mol, yield 48.4%, purity 84.0%).

[0289] The spectral data of the (1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) prepared therefrom are the same as those determined in Example 2-1.

[0290] Examples 2-5

[0291] Preparation of (1,5,5-trimethyl-2-cyclopentenyl)isopropyl acetate (2:R= i Pr; X1, X5, X6, X7=H; X2, X3, X4=Me)

[0292]

[0293] Repeat the steps of Example 2-1, except that bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) obtained according to Examples 1-3 is used. i Pr; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br)(29.12 g: 0.100 mol, purity 95.0%) was used instead of the bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br) used as the reaction substrate in Example 2-1, and vacuum distillation was used instead of silica gel chromatography for purification, thus obtaining (1,5,5-trimethyl-2-cyclopentenyl) isopropyl acetate (2: R = i Pr; X1, X5, X6, X7 = H; X2, X3, X4 = Me)(6.37 g: 0.030 mol, yield 30.3%, purity 84.5%).

[0294] The following is the isopropyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=) prepared from this process. i Various spectral data of Pr; X1, X5, X6, X7 = H; X2, X3, X4 = Me).

[0295] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.93(3H,s),0.97(6H,s),1.24(6H,d,6.0Hz),2.09(1H,dt,J=16.0,1.8Hz),2.15-2.19( 2H,m),2.29(1H,d,13.2Hz),5.01(1H,sep,J=6.6Hz),5.63(1H,dt,J=5.7,2.4Hz),5.79(1H,dt,J=6.0,1.8Hz)ppm. 13C-NMR (126MHz, CDCl3): δ19.98,22.03,22.05,24.05,24.72,41.22,44.22,46.79,50.03,67.43,127.86,139.00,172.80ppm.

[0296] Mass spectrometry EI (70 eV): m / z 210 (M + ),167,153,135,121,109,108,107,93,91,81,67,55,43,27.

[0297] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,741,964,1108,1182,1215,1278,1293,1319,1374,1386,1450,1468,1687,1730,2874,2935,2974,3053.

[0298] Examples 2-6

[0299] Preparation of (1,5,5-trimethyl-2-cyclopentenyl)butyrate (2:R= n Bu; X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0300]

[0301] Repeat the steps of Example 2-1, except that bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) obtained in Examples 1-4 is used. n Bu; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br)(30.53 g: 0.100 mol, purity 84.0%) was used instead of the bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br) used as the reaction substrate in Example 2-1, and the crude product was purified by vacuum distillation instead of silica gel chromatography used in Example 2-1, thus obtaining (1,5,5-trimethyl-2-cyclopentenyl) acetate n-butyl ester (2: R = n Bu; X1, X5, X6, X7 = H; X2, X3, X4 = Me)(4.98 g: 0.022 mol, yield 22.2%, purity 64.5%).

[0302] The following is the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid n-butyl ester (2:R=) prepared from this process. nVarious spectral data for (Bu; X1, X5, X6, X7 = H; X2, X3, X4 = Me).

[0303] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.93-0.95(6H,m),0.97(6H,s),1.35-1.42(3H,m),1.61(3H,quin,J=7.4Hz),2.05(1H,d,J=15.6H z), 2.16-2.21 (2H, m), 2.32 (1H, d, J = 13.2Hz), 4.06 (2H, t, J = 6.6Hz), 5.64 (1H, dt, J = 5.7, 2.6Hz), 5.78 (1H, d, J = 6.0Hz) ppm. 13 C-NMR (126MHz, CDCl3): δ13.85,19.37,20.00,24.11,24.65,30.85,41.00,44.21,46.81,49.98,64.17,127.96,138.96,173.41ppm.

[0304] Mass spectrometry EI (70 eV): m / z 224 (M + ),209,167,153,135,122,109,108,107,93,81,67,55,41,29.

[0305] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,965,1023,1072,1131,1186,1212,1277,1293,1341,1365,1373,1468,1734,2873,2934,2960,3053.

[0306] Examples 2-7

[0307] Preparation of (1,2-dimethyl-2-cyclopentenyl)ethyl acetate (2: R = Et; X3, X4, X5, X6, X7 = H; X1, X2 = Me)

[0308]

[0309] Repeat the steps of Example 2-1, except that bromoacetaldehyde 2,3-dimethyl-2-cyclopentenylethyl acetal (1:R = Et; X3, X4, X5, X6, X7 = H; X1, X2 = Me; Y = Br) (26.32 g: 0.100 mol, purity 87.9%) obtained according to Examples 1-5 is used instead of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R = Et; X3, X4, X5, X6, X7 = H; X1, X2 = Me; Y = Br) used as the reaction substrate in Example 2-1. =Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br), and the crude product obtained was purified by vacuum distillation instead of silica gel chromatography used in Example 2-1, thus obtaining (1,2-dimethyl-2-cyclopentenyl)ethyl acetate (2:R = Et; X3, X4, X5, X6, X7 = H; X1, X2 = Me) (15.13 g: 0.083 mol, yield 83.0%, purity 97.3%).

[0310] The following are the various spectral data of the (1,2-dimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et;X3,X4,X5,X6,X7=H;X1,X2=Me) prepared therefrom.

[0311] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.09 (3H, s), 1.24 (3H, t, J = 7.2Hz), 1.63 (3H, q, J = 1.6Hz), 1.67-1.72 (1H, m), 2.1- 2.15(1H,m),2.17-2.21(2H,m),2.21(1H,d,J=13.2Hz),2.33(1H,d,J=13.2),4.05-4.14(2H,m),5.29(1H,br s,J=1.2Hz)ppm. 13 C-NMR (126MHz, CDCl3): δ12.49,14.40,25.08,29.32,37.12,43.59,48.59,60.12,124.71,145.56,172.53ppm.

[0312] Mass spectrometry EI (70 eV): m / z 182 (M + ),136,94,92,78,77,67,55,53,41,39,29.

[0313] Infrared absorption spectrum (D-ATR): ν (cm) -1 )799,1036,1096,1129,1171,1216,1284,1315,1367,1446,1733,2852,2934,2961,3039.

[0314] Examples 2-8

[0315] Preparation of (4,4-dimethyl-2-cyclopentenyl)ethyl acetate (2: R = Et; X1, X2, X3, X4, X7 = H; X5, X6 = Me)

[0316]

[0317] Repeat the steps of Example 2-1, except that bromoacetaldehyde 5,5-dimethyl-2-cyclopentenylethyl acetal (1:R = Et; X1, X2, X3, X4, X7 = H; X5, X6 = Me; Y = Br) (26.32 g: 0.100 mol, purity 97.7%) obtained according to Examples 1-6 is used instead of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R = Et; X1, X2, X3, X4, X7 = H; X5, X6 = Me; Y = Br) used as the reaction substrate in Example 2-1. =Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br), and the crude product obtained was purified by vacuum distillation instead of silica gel chromatography used in Example 2-1, thus obtaining (4,4-dimethyl-2-cyclopentenyl)ethyl acetate (2:R = Et; X1, X2, X3, X4, X7 = H; X5, X6 = Me) (14.91 g: 0.082 mol, yield 81.8%, purity 81.0%).

[0318] The following are the various spectral data of the (4,4-dimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et;X1, X2, X3, X4, X7=H;X5, X6=Me) prepared therefrom.

[0319] Nuclear magnetic resonance spectroscopy: 1 H-NMR (600MHz, CDCl3): δ1.03(3H,s),1.09(3H,s),1.25-1.29(4H,m),1.96(1H,dd,J=12.6,7.8Hz),2.29(1H,dd,J=15.0,8.4Hz) ,2.40(1H,dd,J=12.0.6.3Hz), 3.16(1H,quin,J=7.5Hz), 4.14(2H,q,J=3.8Hz), 5.48(1H,d,J=5.4Hz), 5.54(1H,d,J=5.5Hz)ppm. 13 C-NMR (150MHz, CDCl3): δ14.43, 28.49, 29.98, 41.24, 41.83, 45.37, 45.79, 60.34, 130.84, 142.45, 173.07ppm.

[0320] Mass spectrometry EI (70 eV): m / z 182 (M + ),167,153,137,121,107,95,93,79,77,67,55,41,28.

[0321] Infrared absorption spectrum (D-ATR): ν (cm) -1 )757,1031,1167,1259,1371,1465,17372864,2955,3041.

[0322] Examples 2-9

[0323] Preparation of (1-methyl-2-cyclopentenyl)ethyl acetate (2: R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me)

[0324]

[0325] Repeat the steps of Example 2-1, except that bromoacetaldehyde ethyl 3-methyl-2-cyclopentenyl acetal (1:R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me; Y = Br) (24.92 g: 0.100 mol, purity 89.9%) obtained in Examples 1-7 is used instead of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me; Y = Br) used as the reaction substrate in Example 2-1. Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me; Y = Br), and the crude product obtained was purified by vacuum distillation instead of silica gel chromatography used in Example 2-1, thus obtaining ethyl acetate (1-methyl-2-cyclopentenyl) (2: R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me) (12.21 g: 0.073 mol, yield 72.6%, purity 97.6%).

[0326] The following are the various spectral data of the (1-methyl-2-cyclopentenyl)ethyl acetate (2: R = Et; X1, X3, X4, X5, X6, X7 = H; X2 = Me) prepared therefrom.

[0327] Nuclear magnetic resonance spectroscopy: 1 H-NMR (600MHz, CDCl3): δ1.14(3H,s),1.25(3H,t,J=6.9Hz), 1.67(1H,dq,J=8.0,6.0Hz), 1.93(1H,dq,J=8.4,6.6Hz),2.32-2.37(m,4H),4.11(2H,q,J=5.4),5.62-5.66(2H,m)ppm. 13C-NMR (150MHz, CDCl3): δ14.44, 26.45, 31.56, 37.15, 45.86, 47.51, 60.11, 129.47, 139.19, 172.38ppm.

[0328] Mass spectrometry EI (70 eV): m / z 168 (M + ),139,122,107,94,81,67,53,41,39,29.

[0329] Infrared absorption spectrum (D-ATR): ν (cm) -1 )739,1035,1120,1290,1317,1340,1367,1454,1733,2852,2868,2957,3051.

[0330] Example 3

[0331] Examples 3-1 to 3-5 below describe a method for preparing (2-cyclopentenyl)acetic acid compound (3), as shown in the following reaction formula.

[0332]

[0333] Example 3-1

[0334] Preparation of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3: X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0335]

[0336] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2:R=Et;X1, X5, X6, X7=H;X2, X3, X4=Me) (19.63 g: 0.100 mol, purity 82.2%), methanol (CH3OH) (70.0 g), and tetrahydrofuran (THF) (150.0 g) obtained according to Example 2-1 were added to the reactor, and the mixture was heated to a liquid temperature of 50°C. A 5% by weight aqueous solution of sodium hydroxide (NaOH aq) (380.0 g: 0.475 mol) at a liquid temperature of 50°C to 55°C was added to the mixture over 2 hours. After the addition was complete, the mixture was stirred at a liquid temperature of 55°C to 60°C for 10 hours.

[0337] After stirring, the reaction mixture was cooled to a liquid temperature of 25°C to 30°C, extracted with n-hexane (100.0 g), and the phases were separated into an organic phase and an aqueous phase. 20% hydrochloric acid (157.0 g) was added dropwise to the aqueous phase at a liquid temperature of 0°C to 10°C to make the mixture acidic. The mixture was then extracted with n-hexane (100.0 g), and the phases were separated into an organic phase and an aqueous phase. The resulting organic phase was washed twice with a 15% sodium chloride aqueous solution (500.0 g). The solvent was removed from the washed organic phase under reduced pressure to obtain (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3: X1, X5, X6, X7 = H; X2, X3, X4 = Me) (16.76 g: 0.099 mol, yield 99.6%, purity 93.2%).

[0338] The (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3:X1,X5,X6,X7=H;X2,X3,X4=Me) prepared in this way has sufficient purity and can be used without purification.

[0339] The following are the various spectral data of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3: X1, X5, X6, X7 = H; X2, X3, X4 = Me) prepared therefrom.

[0340] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.94(3H,s),0.97(3H,s),1.02(3H,s),2.12(1H,dt,J=16.1,2.0Hz), 2.18(1H,dt,J=16.1,2.3Hz), 2.23(1H,d,J=13.8Hz), 2.36(1H,d,J=13.8Hz), 5.66(1H,dt,J=6.1,2.4Hz), 5.80(1H,dt,J=6.1,1.9Hz), 11.53(1H,br)ppm. 13 C-NMR (126MHz, CDCl3): δ19.65, 24.02, 24.37, 40.37, 44.13, 46.58, 49.70, 128.14, 138.44, 179.96ppm.

[0341] Mass spectrometry EI (70 eV): m / z 168 (M + ),153,135,109,93,91,79,67,55,41,27.

[0342] Infrared absorption spectrum (D-ATR): ν (cm) -1)661,716,741,954,1137,1199,1235,1295,1374,1386,1409,1449,1706,2844,2966,3053.

[0343] Example 3-2

[0344] Preparation of 1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3: X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0345]

[0346] The steps of Example 3-1 were repeated, except that the crude (1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et;X1,X5,X6,X7=H;X2,X3,X4=Me) (9.81g:0.050mol, purity 41.8%) obtained according to Example 2-1 was used as the reaction substrate, and thus (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3:X1,X5,X6,X7=H;X2,X3,X4=Me) (8.09g:0.048mol, yield 96.2%, purity 96.1%) was obtained.

[0347] The (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3:X1,X5,X6,X7=H;X2,X3,X4=Me) prepared in this way has sufficient purity and can be used without purification.

[0348] The spectral data of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3: X1, X5, X6, X7 = H; X2, X3, X4 = Me) prepared therefrom are the same as those determined in Example 3-1.

[0349] The results of Examples 3-2 show that even though the ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me) has a low purity, the purity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (3: X1, X5, X6, X7 = H; X2, X3, X4 = Me) prepared therefrom can be increased by alkaline extraction (using an aqueous solution of sodium hydroxide used in hydrolysis to transfer impurities to the aqueous phase).

[0350] Example 3-3

[0351] Preparation of (1,2-dimethyl-2-cyclopentenyl)acetic acid (3: X3, X4, X5, X6, X7 = H; X1, X2 = Me)

[0352]

[0353] The steps of Example 3-1 were repeated, except that ethyl acetate (1,2-dimethyl-2-cyclopentenyl) (2:R=Et; X3, X4, X5, X6, X7=H; X1, X2=Me) (18.23 g: 0.100 mol, purity 89.6%) obtained according to Examples 2-7 was used instead of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) used as the reaction substrate in Example 3-1. Therefore, (1,2-dimethyl-2-cyclopentenyl)acetic acid (3:X3, X4, X5, X6, X7=H; X1, X2=Me) (15.34 g: 0.099 mol, yield 99.5%, purity 98.6%) was obtained.

[0354] The (1,2-dimethyl-2-cyclopentenyl)acetic acid (3: X3, X4, X5, X6, X7 = H; X1, X2 = Me) prepared in this way has sufficient purity and can be used without purification.

[0355] The following are the various spectral data of (1,2-dimethyl-2-cyclopentenyl)acetic acid (3: X3, X4, X5, X6, X7 = H; X1, X2 = Me) prepared therefrom.

[0356] Nuclear magnetic resonance spectroscopy: 1 H-NMR (600MHz, CDCl3): δ1.13 (3H, s), 1.63 (3H, q, J = 1.8Hz), 1.71-1.75 (1H, m), 2.11-2. 16(1H,m),2.20-2.23(2H,m),2.30(1H,d,J=13.2Hz),2.39(1H,d,J=13.8Hz),5.32(1H,br d,J=1.2Hz),10.01(1H,br s)ppm. 13 C-NMR (150MHz, CDCl3): δ12.46, 24.87, 29.32, 37.11, 43.32, 48.46, 124.99, 145.34, 178.88ppm.

[0357] Mass spectrometry EI (70 eV): m / z 154 (M) + ),139,121,94,92,79,67,55,41,39,27.

[0358] Infrared absorption spectrum (ATR): ν (cm) -1)475,664,823,938,1021,1098,1130,1190,1236,1288,1312,1379,1408,1442,1705,2854,2934,2961,3039.

[0359] Examples 3-4

[0360] Preparation of (4,4-dimethyl-2-cyclopentenyl)acetic acid (3: X1, X2, X3, X4, X7 = H; X5, X6 = Me)

[0361]

[0362] The steps of Example 3-1 were repeated, except that ethyl acetate (4,4-dimethyl-2-cyclopentenyl) (2:R=Et; X1, X2, X3, X4, X7=H; X5, X6=Me) (18.23 g: 0.100 mol, purity 82.1%) obtained according to Examples 2-8 was used instead of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) used as the reaction substrate in Example 3-1. Therefore, (4,4-dimethyl-2-cyclopentenyl)acetic acid (3:R=Et; X1, X2, X3, X4, X7=H; X5, X6=Me) (15.05 g: 0.098 mol, yield 97.6%, purity 94.5%) was obtained.

[0363] The (4,4-dimethyl-2-cyclopentenyl)acetic acid (3: X1, X2, X3, X4, X7 = H; X5, X6 = Me) prepared in this way has sufficient purity and can be used without purification.

[0364] The following are the various spectral data of (4,4-dimethyl-2-cyclopentenyl)acetic acid (3:R=Et;X1, X2, X3, X4, X7=H;X5, X6=Me) prepared therefrom.

[0365] Nuclear magnetic resonance spectroscopy: 1H-NMR (600MHz, CDCl3): δ1.04(3H,s),1.10(3H,s),1.30(1H,dd,J=12.6,7.2Hz),2.03(1H,dd,J=12.6,7.8Hz),2.35(1H,dd,J=15.3,8.1 Hz), 2.47(1H,dd,J=15.6,7.2Hz), 3.17(1H,quin,J=7.4Hz), 5.50(1H,dd,J=6.0,1.8Hz), 5.57(1H,dd,J=5.7,2.1Hz), 9.40(1H,brs)ppm. 13 C-NMR (126MHz, CDCl3): δ28.46, 29.95, 40.87, 41.52, 45.42, 45.77, 130.49, 142.77, 179.20ppm.

[0366] Mass spectrometry EI (70 eV): m / z 154 (M) + ),139,121,95,94,79,77,67,55,41,39,27.

[0367] Infrared absorption spectrum (ATR): ν (cm) -1 )675,756,936,1044,1212,1281,1361,1409,1709,2865,2954,3041.

[0368] Examples 3-5

[0369] Preparation of (1-methyl-2-cyclopentenyl)acetic acid (3: X1, X3, X4, X5, X6, X7 = H; X2 = Me)

[0370]

[0371] The steps of Example 3-1 were repeated, except that ethyl acetate (1-methyl-2-cyclopentenyl) (2:R=Et; X1, X3, X4, X5, X6, X7=H; X2=Me) (16.82 g: 0.100 mol, purity 86.9%) obtained according to Examples 2-9 was used instead of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) used as the reaction substrate in Example 3-1. Therefore, (1-methyl-2-cyclopentenyl)acetic acid (3:X1, X3, X4, X5, X6, X7=H; X2=Me) (13.30 g: 0.095 mol, yield 94.9%, purity 98.0%) was obtained.

[0372] The (1-methyl-2-cyclopentenyl)acetic acid (3: X1, X3, X4, X5, X6, X7 = H; X2 = Me) prepared in this way has sufficient purity and can be used without purification.

[0373] The following are the various spectral data of (1-methyl-2-cyclopentenyl)acetic acid (3: X1, X3, X4, X5, X6, X7 = H; X2 = Me) prepared therefrom.

[0374] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.17(3H,s),1.67-1.73(1H,m),1.91-1.96(1H,m),2.34-2.43(4H,m),5.64-5.68(2H,m),11.56(1H,brs)ppm. 13 C-NMR (126MHz, CDCl3): δ26.12, 31.37, 37.10, 45.48, 47.17, 129.64, 138.74, 178.94ppm.

[0375] Mass spectrometry EI (70 eV): m / z 140 (M) + ),122,107,81,80,79,53,41,39.

[0376] Infrared absorption spectrum (ATR): ν (cm) -1 )692,737,924,1100,1127,1246,1289,1315,1353,1375,1409,1706,2868,2957,3051.

[0377] Comparative example

[0378] Comparative Examples 1 and 2 below describe the method described in Non-Patent Document 6 for preparing ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) from 3,4,4-trimethyl-2-cyclopentenyl-1-ol (5: X1, X5, X6, X7 = H; X2, X3, X4 = Me) using the Johnson-Claysen rearrangement reaction, and the method described in Non-Patent Document 6 for preparing ethyl acetate (1,2-dimethyl-2-cyclopentenyl) from 2,3-dimethyl-2-cyclopentenyl-1-ol (5: X3, X4, X5, X6, X7 = H; X1, X2 = Me) using the Johnson-Claysen rearrangement reaction (described in Non-Patent Document 6), and the method described in Non-Patent Document 6 for preparing ethyl acetate (1,2-dimethyl-2-cyclopentenyl) from 2,3-dimethyl-2-cyclopentenyl-1-ol (5: X3, X4, X5, X6, X7 = H; X1, X2 = Me).

[0379] Comparative Example 1

[0380] Preparation of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) (2: R = Et; X1, X5, X6, X7 = H; X2, X3, X4 = Me)

[0381]

[0382] The air in the reactor, equipped with a stirrer, condenser, distillation column, and thermometer, was purged with nitrogen. Then, 3,4,4-trimethyl-2-cyclopenten-1-ol (5:X1, X5, X6, X7 = H; X2, X3, X4 = Me) (12.62 g: 0.100 mol, purity 94.9%), triethyl orthoacetate (CH3C(OEt)3) (81.12 g: 0.500 mol), and propionic acid (C2H5COOH) (0.74 g: 0.010 mol) were added to the reactor. The mixture was then stirred at a liquid temperature of 140°C to 145°C for 38 hours, while refluxed ethanol was distilled off from the top of the distillation column. After stirring, the reaction mixture was cooled to a liquid temperature of 20°C to 25°C. Excess triethyl orthoacetate was removed from the reaction mixture under reduced pressure, and the crude product was then purified by silica gel column chromatography to obtain (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et;X1,X5,X6,X7=H;X2,X3,X4=Me) (5.95 g: 0.030 mol, yield 30.3%).

[0383] The ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) prepared therefrom (2:R=Et; X1, X5, X6, X7=H; X2, X3, X4=Me) 1 The H-NMR (nuclear magnetic resonance) and mass spectrometry data are the same as those determined in Example 2-1.

[0384] The yield of ethyl acetate (1,5,5-trimethyl-2-cyclopentenyl) obtained in Comparative Example 1 was 30.3%, which was lower than the yields of 49.7% in Example 2-1, 47.8% in Example 2-2, 43.9% in Example 2-3, and 48.4% in Example 2-4.

[0385] Comparative Example 2

[0386] Preparation of (1,2-dimethyl-2-cyclopentenyl)ethyl acetate (2: R = Et; X3, X4, X5, X6, X7 = H; X1, X2 = Me)

[0387]

[0388] The steps of Comparative Example 1 were repeated, except that 2,3-dimethyl-2-cyclopenten-1-ol (5:X3,X4,X5,X6,X7=H;X1,X2=Me) (11.22 g: 0.100 mol, purity 93.6%) was used instead of 3,4,4-trimethyl-2-cyclopenten-1-ol (5:X1,X5,X6,X7=H;X2,X3,X4=Me) as the reaction substrate in Comparative Example 1. Thus, (1,2-dimethyl-2-cyclopentenyl)ethyl acetate (2:R=Et;X3,X4,X5,X6,X7=H;X1,X2=Me) (7.49 g: 0.041 mol, yield 41.1%) was obtained.

[0389] The ethyl acetate (1,2-dimethyl-2-cyclopentenyl) prepared therefrom (2:R=Et; X3, X4, X5, X6, X7=H; X1, X2=Me) 1 The H-NMR (nuclear magnetic resonance) and mass spectrometry data are the same as those determined in Examples 2-7.

[0390] The yield of ethyl acetate (1,2-dimethyl-2-cyclopentenyl) obtained in Comparative Example 2 (2: R = Et; X3, X4, X5, X6, X7 = H; X1, X2 = Me) was 41.1%, which was lower than the yield of 83.0% in Examples 2-7.

Claims

1. A method for preparing (2-cyclopentenyl)acetic acid ester compounds of the following general formula (2): (2) Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and X1 to X7 independently represent hydrogen atoms or methyl groups, provided that one to three of X1 to X7 represent methyl groups and the rest represent hydrogen atoms. The method includes: Haloacetal alkyl 2-cyclopentenyl acetals of the following general formula (1): (1) Where R is defined as above, X1 to X7 are selected as in general formula (2), and Y represents a halogen atom. The dehydrohalogenation reaction is carried out in the presence of a base, followed by a rearrangement reaction to form (2-cyclopentenyl)acetic acid ester compound (2).

2. A method for preparing (2-cyclopentenyl)acetic acid compounds of the following general formula (3): (3) Where X1 to X7 are selected as in general formula (1), The method includes: The method for preparing (2-cyclopentenyl) acetate compound (2) according to claim 1; and The (2-cyclopentenyl)acetic acid compound (2) is hydrolyzed to form the (2-cyclopentenyl)acetic acid compound (3).

3. A method for preparing (2-cyclopentenyl)acetic acid ester compounds of the following general formula (2): (2) Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and X1 to X7 independently represent hydrogen atoms or methyl groups, provided that one to three of X1 to X7 represent methyl groups and the rest represent hydrogen atoms. The method includes: Halogenating alkyl vinyl ether compounds of the following general formula (4) with a halogenating agent to form halides; (4) Where R is as defined above, and The halide is subjected to a substitution reaction with a 2-cyclopenten-1-ol compound of the following general formula (5): (5) Where X1 to X7 are selected as in general formula (2), To form alkyl 2-cyclopentenyl acetals of the following general formula (1): (1) Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, X1 to X7 are selected from general formula (2), and Y represents a halogen atom; and The haloacetal alkyl 2-cyclopentenyl acetal compound (1) is subjected to dehydrohalogenation in the presence of a base, followed by a rearrangement reaction to form (2-cyclopentenyl) acetate compound (2).

4. A method for preparing (2-cyclopentenyl)acetic acid compounds of the following general formula (3): (3) Where X1 to X7 are selected as in general formula (1), The method includes: The method for preparing (2-cyclopentenyl) acetate compound (2) according to claim 3; and The (2-cyclopentenyl)acetic acid compound (2) is hydrolyzed to form the (2-cyclopentenyl)acetic acid compound (3).

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