JP2001139504A - Deuterium-labeled styrene trimer and method for determination of styrene trimer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a deuterium-labeled styrene trimer and a high-accuracy determination process using the same. SOLUTION: This invention provides a deuterium-labeled styrene trimers represented by the formulas (I), (II) and (III) [where R1 and R2 are each H, or D(deuterium); R3 is phenyl group or a phenyl group of which all of the hydrogen atoms on the benzene rings are substituted by deuterium atoms; C6D5 means that the all of the hydrogen atoms on a phenyl ring are substituted with D; the compounds of formula (II) include four kinds of stereoisomers; the compounds of formula (III) include two kinds of stereoisomers]. Thus, these isomers can be separated from each other and purified and the high-exact determination of styrene trimer can be achieved by utilizing these isomers.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for quantitatively analyzing styrene oligomers present in a polystyrene product requiring a complicated pretreatment, wherein a loss in the pretreatment is corrected.
The present invention relates to a deuterium-labeled styrene trimer useful for quantifying an appropriate amount of a styrene oligomer and a method for producing the same, and a high-precision analysis method for a styrene trimer to which the surrogate compound is added as an internal standard for analysis.

[0002]

2. Description of the Related Art Since the topic of environmental hormones has become a topic, analysis of styrene oligomers present in polystyrene products has been widely conducted, and it has been revealed that there are several types of styrene oligomers that are considered to be present. afterwards,
The focus of the world has shifted to how much styrene oligomers are transferred into foods in actual meal forms. However, in the meal form, unless the fats and oils component contained in the meal is removed, the analysis becomes extremely difficult due to the influence of impurities, so that several steps of pretreatment must be performed.

[0003] In the quantitative analysis of a compound requiring a complicated pretreatment, when performing an analysis using a GC-MS or LC-MS method, a Good Laboratory Practice (GLP) is used.
tice), a reagent labeled with [ ¹³ C ₁₂ ] or [ ² H ₁ ] (deuterium atom) as a surrogate compound or an internal standard substance was added to confirm the extraction efficiency, and pretreatment was performed based on the addition recovery rate. A method for compensating for the loss at the stage is recommended.

[0004] Polystyrene is a polymer obtained by polymerizing styrene, and is widely used for food containers and the like. A small amount of styrene oligomer is present in polystyrene, and its content varies depending on the method or type of polystyrene.

Kawamura et al. Identified styrene oligomers contained in general-purpose polystyrene, which is a styrene homopolymer, and determined or estimated the structures of several styrene dimers and styrene trimers [Food Sanitation] Academic Journal, Vol. 39, No. 2, p. 110 (1998)]. Kawamura et al. Established a method for the analysis of styrene dimers and trimers in instant noodles in polystyrene containers [Food Hygiene Magazine, Vol. 39, No. 5, p. 310 (1998)], and found that styrene oligomers in polystyrene were present. Report that some of them migrate into foods (Food Hygiene Magazine, Vol. 39, No. 6, page 390 (1998)).

[0006] In the transfer test to food, complicated pre-treatment is required, and during the pre-treatment, a part of the styrene oligomer to be originally detected is lost, and it is possible to quantify the styrene oligomer less than the true value. There is. Kawamura et al. Conducted a spike recovery experiment and found that the spike recovery rate was 77.5 to 77.5.
Although it is stated that it does not affect the actual analysis because it is as high as 111.7%, it is hard to say that an appropriate quantitative result has been obtained because there is a maximum variation of about 20% in this recovery experiment. . Further, when a solution containing a styrene trimer is dried or concentrated, there is a concern that the styrene trimer may volatilize together with the solution.

Therefore, as described above, styrene trimer
Analysis by GC-MS or LC-MS method
When conducting Good Laboratory Practices (G
LP; Good Laboratory Practi
ce) as recommended by
Rogate compounds and internal standards [¹³C₁₂] Or [ ^Two
H₁] (Deuterium atom), and add the reagent.
The loss in the pretreatment stage from the spike recovery rate
A way was sought.

[0008] A problem in performing the analysis using a surrogate compound is that when the fragment peak of the surrogate compound overlaps with the monitor ion of the measured compound, the peak intensity of the monitor ion of the measured compound is added by the intensity of the fragment peak. And a peak much larger than the actual value is detected. Therefore, in order to use a fragment peak having a higher ionic strength as a monitor ion peak of a measured compound in order to raise the calibration limit, it is necessary to design deuterium substitution in consideration of the fragment in the mass spectrum of each compound.

The linear styrene trimers 2,4
When the mass spectrum of 6-triphenyl-1-hexene is analyzed, the parent peak 312 is detected, but is much smaller than the reference peak 91. The fragment peak of 91 indicates that of an alkyl-substituted phenyl group, and in order to use this reference peak as a monitor ion of 2,4,6-triphenyl-1-hexene, it was bonded to the benzene ring. All hydrogen atoms need to be replaced with deuterium atoms.

Further, 1-phenyl-4- (1-phenylethyl) tetralin or 1-phenyl-4- (2-phenylene) which is a styrene trimer having a tetralin ring in the molecule is used.
With respect to (phenylethyl) tetralin, the substituent bonded to the 4-position of the tetralin ring is very likely to be eliminated, so that the parent peak 312 is not detected at all in 1-phenyl-4- (1-phenylethyl) tetralin, Also, 1-
Only a very small amount of phenyl-4- (2-phenylethyl) tetralin is detected, and as a remarkable ion peak, 9
1, 129 and 207. The fragment of 129 is derived from a tetralin ring, and the fragment of 207 is a fragment obtained by removing the substituent bonded to the 4-position of the tetralin ring from each compound. Therefore, in order to use 129 and 207 as monitor ions of these compounds, it is necessary that at least the hydrogen atom of the benzene ring or tetralin ring at the 1-position is substituted with a deuterium atom. Further, in order to use 91 as a monitor ion, all hydrogen atoms bonded to the benzene ring must be replaced with deuterium atoms.

[0011] As the surrogate compound corresponding to 2,4,6-phenyl-1-hexene, 2,4,6-triphenyl-1-hexene -d ₅ is produced by Wako Pure Chemical Industries, Ltd. and HayashiJunyaku industrial It is commercially available from Co., Ltd. and has the following structure A, B or C.

[0012]

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[In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on the benzene ring have been substituted with deuterium atoms. ]

However, in any of the three benzene rings, the hydrogen atom on any one of the three benzene rings is replaced with a deuterium atom. As a group, in addition to 96 of deuterated benzyl, 91 of non-deuterated benzyl may also be detected.
Since this peak overlaps with 91, which is the reference peak of 4,6-triphenyl-1-hexene, this 91 peak cannot be used as a measurement ion, and it is difficult to quantify it accurately.

On the other hand, for 1-phenyl-4- (1-phenylethyl) tetralin and 1-phenyl-4- (2-phenylethyl) tetralin, there are no reports on the corresponding surrogate compounds. In addition, there is no report of high-precision analysis of styrene trimer using these surrogate compounds.

[0016]

SUMMARY OF THE INVENTION An object of the present invention is to provide a polyvalent deuterated product in which a deuterium atom is introduced into a fragment peak having a high peak intensity so as not to lower the limit of quantification. A surrogate compound in which all hydrogen atoms bonded to three benzene rings of 2,4,6-triphenyl-1-hexene, which is a linear styrene trimer, are substituted with deuterium atoms, and tetralin 5 or 6 of at least the tetralin ring of 1-phenyl-4- (1-phenylethyl) tetralin or 1-phenyl-4- (2-phenylethyl) tetralin, which is a styrene trimer having a ring in the molecule.
Provided is a surrogate compound in which hydrogen atoms bonded to the 7- and 8-positions and all hydrogen atoms bonded to the benzene ring in the 1-position are substituted with deuterium atoms, and a high-precision analysis method for styrene trimers using the surrogate compounds. I will provide a.

[0017]

Means for Solving the Problems The present invention provides the following items 1-1.
5 is provided.

Item 1. General formula (I)

[0019]

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A compound represented by the formula: [Wherein, R ¹ and R ^{2 each} represent a hydrogen atom or a deuterium atom; C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ]

Item 2. General formula (II-1)

[0022]

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A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ]

Item 3. General formula (II-2)

[0025]

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A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ]

Item 4. General formula (II-3)

[0028]

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A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ]

Item 5. General formula (II-4)

[0031]

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A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ]

Item 6. General formula (III-1)

[0034]

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A compound represented by the formula: [Wherein, R ³ represents a phenyl group or a phenyl group in which all hydrogen atoms on a benzene ring have been replaced by deuterium atoms; C ₆ D ₅ has all hydrogen atoms on the benzene ring replaced by deuterium atoms] Indicates a phenyl group. ]

Item 7. General formula (III-2)

[0037]

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A compound represented by the formula: [Wherein, R ³ represents a phenyl group or a phenyl group in which all hydrogen atoms on a benzene ring have been replaced by deuterium atoms; C ₆ D ₅ has all hydrogen atoms on the benzene ring replaced by deuterium atoms] Indicates a phenyl group. ]

Item 8. A process for producing a compound represented by the general formula (I), characterized by a carbon-addition reaction to the compound represented by the general formula (IV).

[0040]

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[In the formula, R ¹ and R ^{2 each} represent a hydrogen atom or a deuterium atom; C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ]

Item 9. A method for producing a compound represented by the general formula (II), comprising reducing the compound represented by the general formula (V).

[0043]

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[In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on the benzene ring have been replaced with deuterium atoms. ]

Item 10. A method for producing a compound represented by the general formula (III), comprising reducing the compound represented by the general formula (VI).

[0046]

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[Wherein, R ³ represents a phenyl group or a phenyl group in which all hydrogen atoms on a benzene ring are substituted with deuterium atoms; C ₆ D ₅ represents all hydrogen atoms on a benzene ring are deuterium atoms. Indicate a substituted phenyl group. ]

Item 11. Items 2 to 5 wherein the stereoisomers of the compound of the general formula (II) obtained in Item 9 are separated.
A method for producing a compound according to any one of the above.

Item 12. General formula (III) obtained in item 10
Item 6 is a step of separating stereoisomers of the compound of
Or a method for producing the compound according to 7.

Item 13. Item 8. An internal standard for analysis comprising the compound according to any one of Items 1 to 7.

Item 14. Item 14. A method for quantifying a styrene trimer, comprising the step of adding the internal standard substance for analysis according to Item 13 to a styrene trimer quantitative test solution.

Item 15. A method for quantifying the amount of styrene trimer eluted into food packed in a polystyrene container,
The styrene trimer quantitative test solution is a homogenized liquid food or hot food or water which is poured into hot water or water into a polystyrene container filled with food or eaten into hot water or water. Item 15. The method for quantifying a styrene trimer according to Item 14, which is a solution containing a liquid.

[0053]

BEST MODE FOR CARRYING OUT THE INVENTION The compound represented by the general formula (I) in the present invention can be produced according to the following <Reaction Scheme 1>. <Reaction process formula 1>

[0054]

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[Wherein R ¹ and R ^{2 each} represent a hydrogen atom or a deuterium atom; C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been replaced by deuterium atoms;
Represents a trimethylsilyl group. ]

(Step A) First, 1 mol of the compound represented by the formula (2) is added to 1 mol of the compound represented by the formula (1) in the presence of a Lewis acid at -78 ° C. to the reflux temperature of the solvent. And 10
The compound represented by the formula (3) can be obtained by reacting for minutes to 24 hours.

The compound represented by the formula (1) used in this reaction can be obtained by the method described in Japanese Patent Application No. 11-127517. The compound represented by the formula (2) is commercially available acetophenone-2 ′, 3 ′, 4 ′, 5 ′, 6′-d
_It can be obtained by a reaction between ₅ and chlorotrimethylsilane under basic conditions. Here, the base includes lithium diisopropylamide and the like.

The Lewis acid in this reaction includes titanium (IV) chloride, tin (IV) chloride, boron trifluoride etherate and the like.

This reaction is usually carried out in a solvent, such as dichloromethane, chloroform, diethyl ether,
Tetrahydrofuran and the like.

(Step B) Next, 1 mole of the compound represented by the formula (3) is reacted with 1 to 10 moles of a dehydrating reagent at a temperature from room temperature to a reflux temperature of the solvent for 1 to 5 hours to obtain a compound of the formula (4) )
Can be obtained.

The compound represented by the formula (4) obtained in this reaction refers to all α, β-unsaturated ketones, β, γ-unsaturated ketones and their respective cis and trans geometric isomers. Further, these can be separated and purified by using silica gel chromatography, high performance liquid chromatography and the like.

In the present reaction, examples of the dehydrating reagent include methanesulfonyl chloride, p-toluenesulfonyl chloride, trifluoroacetic anhydride, thionyl chloride and the like.

This reaction can be carried out without solvent or in a solvent such as chloroform, dichloromethane, N, N-dimethylformamide, pyridine and the like.

(Step C) Next, the compound represented by the formula (4) is subjected to a catalytic hydrogenation reaction in the presence of a catalyst at room temperature for 10 minutes to
By performing the reaction for 10 hours, the compound represented by the formula (IV) can be obtained.

The catalyst in this reaction includes palladium-activated carbon and the like. This reaction is usually performed in a solvent, and examples of the solvent include n-hexane, ethyl acetate, methanol, ethanol, and acetic acid.

(Step D) Finally, 1 mol of the compound represented by the formula (IV) is reacted with 1 to 10 mol of the Wittig reagent at a temperature of 0 ° C. to reflux of the solvent for 10 minutes to 10 hours. The compound of the present invention represented by (I) can be obtained.

The Wittig reagent in this reaction is PP
h ₃ ＣＨCH ₂ and the like, and can be obtained by reacting methyltriphenylphosphonium bromide and the like with a base such as n-butyllithium in a solvent such as diethyl ether and tetrahydrofuran.

This reaction is usually carried out in a solvent, and examples of the solvent include diethyl ether and tetrahydrofuran.

The compound represented by the formula (IV) can also be produced according to the following <reaction process formula 2>. <Reaction process formula 2>

[0070]

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[Wherein R ¹ and R ^{2 each} represent a hydrogen atom or a deuterium atom; C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on the benzene ring have been replaced by deuterium atoms. ]

(Step E) 1 mol of the Grignard reagent represented by the formula (6) is reacted with 1 mol of the deuterated chalcone (5) at a temperature of 0 ° C. to reflux of the solvent for 10 minutes to 24 hours. Thereby, the compound represented by the formula (IV) can be obtained.

This reaction is usually performed in a solvent, and examples of the solvent include ether solvents such as diethyl ether and tetrahydrofuran.

The deuterated chalcone used in this reaction can be obtained by the method described in Japanese Patent Application No. 11-127517. The Grignard reagent can be obtained by reacting deuterated phenethyl halide with magnesium. The deuterated phenethyl halide can be obtained, for example, by the following <
It can be synthesized according to the reaction scheme 3>. <Reaction process formula 3>

[0075]

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[Wherein, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on the benzene ring have been replaced with deuterium atoms. ]

(Step F) By reacting 1 to 2 mol of chloroacetyl chloride with benzene-d ₆ (7) in the presence of aluminum chloride at room temperature to a temperature at which the solvent is refluxed for 30 minutes to 24 hours, ) Can be obtained.

This reaction is carried out without solvent or with dichloromethane,
It can be performed in a solvent such as chloroform or carbon disulfide.

(Step G) 1 mol of the compound represented by the formula (8) is reacted with 2 to 10 mol of triethylsilane in trifluoroacetic acid at a temperature from room temperature to a reflux temperature of the solvent for 1 to 48 hours. The compound represented by (9) can be obtained.

The compound represented by the general formula (II) in the present invention can be produced according to the following <Reaction Scheme 4>. <Reaction process formula 4>

[0081]

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[Wherein, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on the benzene ring have been substituted with deuterium atoms. ]

(Step H) First, benzonitrile (10)
One mole of Grignard reagent (C ₆ D ₅ CD ₂ MgB
r) 1 to 10 moles at 0 ° C to the reflux temperature of the solvent
After reacting for 0 minutes to 24 hours, the compound represented by the formula (11) can be obtained by performing a substitution reaction of a deuterium atom → a hydrogen atom in an alcohol solvent under basic conditions.

As the benzonitrile used in this reaction, commercially available products and the like can be used. Further, Grignard reagent may be used those obtained by reaction with benzyl bromide -d ₇ and magnesium brominated commercially or toluene -d _8.

This reaction is usually carried out in a solvent, and examples of the solvent include ether solvents such as diethyl ether and tetrahydrofuran.

The base in the substitution reaction from a deuterium atom to a hydrogen atom includes sodium methoxide, potassium t-butoxide and the like, and the alcohol-based solvent refers to, for example, methanol, ethanol and butanol.

(Step I) Compound 1 represented by Formula (11)
The compound represented by the formula (13) can be obtained by reacting 1 to 10 mol of the compound represented by the formula (12) with the mol under basic conditions at 0 ° C. to room temperature for 1 to 24 hours.

As the compound represented by the formula (12) used in this reaction, a compound produced according to the following <reaction process formula 5> can be used.

The base mentioned here includes sodium hydride and the like. This reaction is usually performed in a solvent, and examples of the solvent include N, N-dimethylformamide, dimethyl sulfoxide and the like.

(Step J) Next, the compound of the formula (13) is reacted under an acidic condition at 80 ° C. to a reflux temperature of the solvent for 1 to 60 hours.
The compound represented by the formula (14) can be obtained by reacting for a time.

The compound represented by the formula (14) refers to all stereoisomers, and these can be separated and purified by using silica gel chromatography or the like.

In this reaction, examples of the acid include p-toluenesulfonic acid and the like, and the presence of silica gel or the like can further promote the reaction.

This reaction can be carried out without a solvent or in a solvent such as benzene, toluene, xylene or mesitylene.

(Step K) Subsequently, 1 to 10 moles of a reagent for generating a methyl anion in 1 mole of the compound represented by the formula (14) are added at 0 ° C. to a reflux temperature of the solvent for 1 to 24 hours.
The compound represented by the formula (15) can be obtained by reacting for a time.

The compound represented by the formula (15) refers to all stereoisomers, and these can be separated and purified by using silica gel chromatography, high performance liquid chromatography and the like. is there.

In the present reaction, examples of the compound capable of generating a methyl anion include Grignard reagents such as methylmagnesium bromide and organometallic compounds such as methyllithium.

This reaction is usually carried out in a solvent, and examples of the solvent include ether solvents such as diethyl ether and tetrahydrofuran.

(Step L) Next, 1 mole of the compound represented by the formula (15) is reacted with 1 to 10 moles of a dehydrating reagent at a temperature from room temperature to a reflux temperature of the solvent for 1 to 5 hours to obtain a compound of the formula (V) ) Can be obtained.

The compound represented by the formula (V) obtained in this reaction includes those in which the dehydration reaction has proceeded to the exomethylene type, those in the tetrasubstituted form, It refers to each positional isomer of isomerization and all of these stereoisomers. These can be separated and purified by using silica gel chromatography, high performance liquid chromatography and the like.

In the present reaction, examples of the dehydrating reagent include methanesulfonyl chloride, p-toluenesulfonyl chloride, trifluoroacetic anhydride, thionyl chloride and the like.

This reaction can be carried out without solvent or in a solvent such as chloroform, dichloromethane, N, N-dimethylformamide, pyridine and the like.

(Step M) Finally, the compound represented by the formula (II) represented by the formula (II) is obtained by subjecting the compound represented by the formula (V) to a catalytic hydrogenation reaction in the presence of a catalyst at room temperature for 10 minutes to 10 hours. A compound can be obtained.

The compound of the present invention represented by the formula (II) is 1S
^* - phenyl -4S ^* - (1R ^* - phenylethyl) tetralin -d _10, 1S ^* - phenyl -4R ^* - (1S ^* - phenylethyl) tetralin -d _10, 1S ^* - phenyl -
4S ^* - (1S ^* - phenylethyl) tetralin -d _10,
1S ^* -phenyl-4R ^* -(1R ^* -phenylethyl)
Refers to all things -d _10, they can be separated and purified by using high performance liquid chromatography.

The catalyst in the present reaction includes palladium-activated carbon and the like. This reaction is usually performed in a solvent, and examples of the solvent include n-hexane, ethyl acetate, methanol, ethanol, and acetic acid.

The compound represented by the formula (12) in the above <Reaction Scheme 4> can be produced according to the following <Reaction Scheme 5>. <Reaction process formula 5>

[0106]

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[Wherein R ⁴ represents lower alkyl such as methyl, ethyl, propyl, etc .; C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on the benzene ring have been replaced by deuterium atoms. ]

(Step N) First, benzaldehyde-d ₆
(16) Horner-Emmons reagent 1 to 1 mol
10 minutes from 0 ° C. to the reflux temperature of the solvent for 5 minutes to 24 hours.
The compound represented by the formula (17) can be obtained by reacting for a time.

The Horner-Emmons reagent can be obtained by reacting a trialkyl phosphonoacetate with sodium hydride. Here, alkyl refers to lower alkyl such as methyl, ethyl and propyl.

This reaction is usually performed in a solvent, and examples of the solvent include benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, n-hexane, diethyl ether, tetrahydrofuran, and N, N-dimethylformamide.

The benzaldehyde-d used in this reaction
_{For 6} , a commercially available product can be used.

(Step O) Subsequently, 1 mol of the compound represented by the formula (17) is reacted with 1 to 1.5 mol of a reducing reagent at -78 ° C. to room temperature for 10 minutes to 24 hours to obtain the compound represented by the formula (1).
The compound represented by 8) can be obtained.

The reducing reagent mentioned here includes diisobutylaluminum hydride and the like.

This reaction is usually performed in a solvent, and examples of the solvent include benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, n-hexane, diethyl ether, tetrahydrofuran and the like.

(Step P) Finally, 1 to 10 mol of a brominating agent is added to 1 mol of the compound represented by the formula (18) in the presence of 1 to 2 mol of triphenylphosphine at 0 ° C. to room temperature for 5 min. 1
By reacting for 0 hour, the compound represented by the formula (12) can be obtained.

The brominating agent mentioned here includes N-bromosuccinimide, carbon tetrabromide and the like.

This reaction is usually performed in a solvent, and examples of the solvent include dichloromethane, chloroform and the like.

The present inventors clarified the relative configuration of the present compound by comparing the physical properties of the compound of the present invention with the compound described in Japanese Patent Application No. 10-371350. The relationship between the structure and the retention time of gas chromatography and high performance liquid chromatography of the present compound under the following analysis conditions is as follows ^: 1S ^* -phenyl-4S ^* -
(1R ^* - phenylethyl) tetralin -d _10, 1S ^* -
Phenyl -4R ^* - (1S ^* - phenylethyl) tetralin -d _10, 1S ^* - phenyl -4S ^* - (1S ^* - phenylethyl) tetralin -d _10, 1S ^* - phenyl -4R ^*
- (1R ^* - phenylethyl) tetralin -d _10.

Analytical conditions (gas chromatography) Column: DB-WAX (0.25 mmid × 30)
m, df = 0.25 μm) Column temperature: 160 ° C. → 8 ° C./min. → 240 ° C (3
0 min. Inlet temperature: 240 ° C Detector temperature: 240 ° C Carrier gas: He (1.35 mL / min.) Analysis conditions (high-performance liquid chromatography) Column: TSKgel ODS-80TSQA (4.6)
mm × 250 mm) Column temperature: 50 ° C. Mobile phase: 85% methanol, 15% water Flow rate: 1.5 mL / min. Detection wavelength: 254 nm

The compound represented by the general formula (III) in the present invention can be produced according to the following <Reaction Scheme 6>. <Reaction process formula 6>

[0121]

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[Wherein, R ³ represents a phenyl group or a phenyl group in which all hydrogen atoms on a benzene ring are substituted with deuterium atoms; R ⁵ represents a lower alkyl such as methyl, ethyl, propyl; ₆ D ₅ represents a phenyl group in which all hydrogen atoms on the benzene ring have been replaced by deuterium atoms. ]

(Step Q) First, benzophenone-d
₁₀ (19) Horner-Emmons reagent 1 in 1 mol
10 to 10 mol at 0 ° C. to the reflux temperature of the solvent for 5 minutes to 2
By reacting for 4 hours, the compound represented by the formula (20) can be obtained.

The Horner-Emmons reagent can be obtained by reacting a trialkyl phosphonoacetate with sodium hydride. Here, alkyl refers to lower alkyl such as methyl, ethyl and propyl.

This reaction is usually carried out in a solvent, and examples of the solvent include benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, n-hexane, diethyl ether, tetrahydrofuran, N, N-dimethylformamide and the like.

[0126] Benzophenone -d ₁₀ used in this reaction can be used a commercially available product.

(Step R) Next, the compound represented by the formula (21) is subjected to a catalytic hydrogenation reaction at room temperature for 10 minutes to 10 hours in the presence of a catalyst. Obtainable.

The catalyst in this reaction includes palladium-activated carbon and the like. This reaction is usually performed in a solvent, and examples of the solvent include n-hexane, ethyl acetate, methanol, ethanol, and acetic acid.

(Step S) Compound 1 represented by Formula (21)
The compound represented by the formula (22) can be obtained by reacting 2 to 6 moles of the reducing reagent at a temperature of from room temperature to the reflux temperature of the solvent for 1 to 6 hours.

The reducing reagent mentioned here includes, for example, lithium borohydride, sodium borohydride, lithium aluminum hydride, diisobutylaluminum hydride and the like.

This reaction is usually performed in a solvent, and examples of the solvent include dioxane, tetrahydrofuran, diethyl ether, ethyl acetate, methanol, ethanol and the like.

(Step T) Compound 1 represented by Formula (22)
The compound represented by the formula (23) can be obtained by reacting 1 to 3 moles of the chlorinating agent with each other at a temperature of 0 ° C. to the reflux temperature of the solvent for 1 to 24 hours.

The chlorinating agent mentioned here includes, for example, thionyl chloride, N-bromosuccinimide in the presence of triphenylphosphine, carbon tetrachloride and the like.

This reaction can be carried out without solvent or in a solvent such as dioxane, tetrahydrofuran, diethyl ether, n-hexane, cyclohexane, dichloromethane, chloroform, benzene or xylene.

(Step U) Compound 1 represented by Formula (23)
The compound represented by the formula (24) can be obtained by reacting 1 to 2 mol of a metal cyanide at room temperature to a reflux temperature of a solvent for 1 to 60 hours under a potassium iodide catalyst.

The metal cyanide in this reaction includes sodium cyanide, potassium cyanide and the like.

This reaction is usually performed in a solvent, and can be performed in a solvent such as N, N-dimethylformamide, dimethylsulfoxide and the like.

(Step V) Next, 1 mol of the compound represented by the formula (24) is subjected to a hydrolysis reaction under basic conditions at a temperature from room temperature to reflux for 1 to 24 hours to give a compound of the formula (25)
Can be obtained.

In the present reaction, examples of the base catalyst include aqueous solutions of alkali metal hydroxides such as lithium hydroxide, potassium hydroxide and sodium hydroxide, and alkali metal carbonates such as sodium carbonate and potassium carbonate.

This reaction is usually carried out in a solvent, and examples of the solvent include methanol, ethanol, dioxane, tetrahydrofuran, ethylene glycol monomethyl ether and the like.

(Step W) Subsequently, 1 mol of the compound represented by the formula (25) is reacted with 1 to 2 mol of thionyl chloride at a temperature from room temperature to a reflux temperature of the solvent for 1 to 24 hours to give the compound of the formula (26) ) Can be obtained.

This reaction can be carried out without solvent or in a solvent such as dioxane, tetrahydrofuran, diethyl ether, n-hexane, cyclohexane, dichloromethane, chloroform, benzene, xylene, N, N-dimethylformamide.

(Step X) Next, one mole of the compound represented by the formula (26) is reacted in the presence of aluminum chloride at 0 ° C. to a reflux temperature of the solvent for 1 to 5 hours to give the compound of the formula (27) Can be obtained.

This reaction can be carried out without solvent or in a solvent such as dichloromethane, chloroform or carbon disulfide.

(Step Y) Next, 1 mol of the compound represented by the formula (28) is added to 1 mol of the Grignard reagent represented by the formula (28) at 1 ° C. under a temperature at which the solvent is refluxed.
By reacting for 5 hours, a compound represented by the formula (29) can be obtained.

The G represented by the formula (28) used in this reaction formula
As the reagent, it is possible to use a commercially available product or a compound obtained by reacting a compound synthesized by the above <Reaction process formula 3> with magnesium.

This reaction is usually carried out in a solvent, and examples of the solvent include ether solvents such as diethyl ether and tetrahydrofuran.

(Step Z) Next, 1 mol of the compound represented by the formula (29) is reacted with 1 to 10 mol of a dehydrating reagent at a temperature from room temperature to a reflux temperature of the solvent for 1 to 5 hours to obtain a compound of the formula (V
The compound represented by I) can be obtained.

The compound represented by the formula (VI) obtained in this reaction refers to all of the regioisomers in which the dehydration reaction has proceeded outside the tetralin ring and in which the dehydration reaction has proceeded inside the tetralin ring. These can be separated and purified by using silica gel chromatography, high performance liquid chromatography and the like.

In the present reaction, examples of the dehydrating reagent include methanesulfonyl chloride, p-toluenesulfonyl chloride, trifluoroacetic anhydride, thionyl chloride and the like.

This reaction can be carried out without solvent or in a solvent such as chloroform, dichloromethane, N, N-dimethylformamide, pyridine and the like.

(Step AA) Finally, the compound represented by the formula (VI) is subjected to a catalytic hydrogenation reaction in the presence of a catalyst at room temperature for 1 to 4 hours.
By conducting the reaction for 10 hours, the compound of the present invention represented by the formula (III) can be obtained.

The compound of the present invention represented by the formula (III)
S ^* - phenyl -d ₅ -4S ^* - (2- phenylethyl)
Tetralin-5,6,7,8-d ₄ , 1S ^* -phenyl-
d ₅ -4R ^* - (2- phenylethyl) tetralin -5,
6, 7, 8-d ₄ and, 1S ^* - phenyl -d ₅ -4S ^* -
(2-phenyl -d ₅ - ethyl) tetralin -5,6,
7,8-d _4, 1S ^* - phenyl -d ₅ -4R ^* - (2- phenyl -d ₅ - ethyl) tetralin -5,6,7,8
refers to all that the d _4, they can be separated and purified by using high performance liquid chromatography.

Examples of the catalyst in this reaction include palladium on activated carbon. This reaction is usually performed in a solvent, and examples of the solvent include n-hexane, ethyl acetate, methanol, ethanol, and acetic acid.

The present inventors have clarified the relative configuration of the present compound based on the result of analysis by X-ray crystal analysis. The relationship between the structure and the retention time of gas chromatography and high performance liquid chromatography of the present compound under the following analysis conditions was as follows: from the short retention time to 1S ^* -phenyl-d ₅
-4R ^* -(2-phenylethyl) tetralin-5,
6,7,8-d _4, 1S ^* - phenyl -d ₅ -4S ^* - (2
-Phenylethyl) tetralin-5,6,7,8-d ₄
Or, 1S ^* - phenyl -d ₅ -4R ^* - (2- phenyl -d ₅ - ethyl) tetralin -5,6,7,8
d _4, 1S ^* - phenyl -d ₅ -4S ^* - (2- phenyl -
d ₅ - ethyl) tetralin -5,6,7,8-d _4.

Analysis conditions (gas chromatography) Column: DB-WAX (0.25 mmid × 30)
m, df = 0.25 μm) Column temperature: 100 ° C. → 20 ° C./min. → 250 ° C
(30 min.) Inlet temperature: 250 ° C Detector temperature: 250 ° C Carrier gas: He (1.3 mL / min.) Analysis conditions (high-performance liquid chromatography) Column: TSKgel ODS-80TSQA (4.6)
mm × 250 mm) Column temperature: 50 ° C. Mobile phase: 80% acetonitrile, 20% water Flow rate: 1.5 mL / min. Detection wavelength: 254 nm

The compounds of the present invention represented by formulas (I), (II) and (III) are deuterium-labeled styrene trimers which are said to be present in polystyrene products;
These chemistries are almost identical to the corresponding styrene trimers. In addition, since the fragment pattern in the mass spectrum was analyzed in detail and the substitution position of deuterium was designed, quantitative analysis of styrene oligomers using not only the parent peak of each compound but also the fragment peak showing strong intensity can be performed. Possible surrogate compounds. Therefore, it is a very effective internal standard in the quantitative test of the amount of styrene trimer in polystyrene products that requires complicated pretreatment. Further, the method for analyzing styrene trimer using the compound of the present invention is a very high-precision analysis method in which the loss of styrene trimer, which is unavoidable in operation, is corrected.

Next, the method for quantifying the styrene trimer will be described in three different ways: a method for quantifying the amount of polystyrene material, a method for quantifying the amount of elution from the polystyrene container, and a method for quantifying the amount of elution to food in the polystyrene container. I do.

<Quantitative method 1> Included in polystyrene material
Determination method of styrene trimer
The contact is carried out for 10 minutes to 100 hours at a temperature from C to reflux of the solvent. This is used as a quantitative test solution (a diluted solution of the contacted solution may be used as a quantitative test solution), and 0.1 μg to 10 mg of the compound of the present invention (analytical internal standard substance) is added. Dilute with a solvent if necessary, and use the internal standard (p
-Terphenyl or the like can be used) to prepare a measurement sample. The amount of the styrene trimer and the recovery of the compound of the present invention added are quantified by GC-MS or LC-MS.

Correction calculation was performed according to the formula (amount of styrene trimer contained in polystyrene material) = (quantification result of styrene trimer) ÷ (addition and recovery rate of surrogate compound), and the true value of the amount of styrene trimer in the polystyrene material was calculated. obtain.

The measurement sample referred to herein is EPS (expa
ndable polystyrene) beads, PS
P (polystyrene paper) resin, H
IPS (high impact polystyle)
ne) Resin, EPS (expandable pol)
ystyrene) cup, PSP (polystyr)
ene paper cup, HIPS (high i)
and polystyrene products such as polystyrene buffers.

The solvent referred to herein is n-hexane,
Examples include n-heptane, n-pentane, cyclohexane, methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, chloroform, methylene chloride, and a mixed solvent thereof. Further, as the diluting solvent used here, the same solvents as those described above can be used.

[0163] vinegar from <Quantitative Method 2> polystyrene containers
Quantitative method of elution amount of Tylene trimer 100 mg to 1 kg of a measurement sample and 1 mL to 1 L of a solvent were
The contact is carried out for 10 minutes to 100 hours at a temperature from C to reflux of the solvent. A liquid layer of 1 μL to 100 mL is measured and used as a quantitative test solution (a solution obtained by concentrating or diluting the measured solution can be used as a quantitative test solution) of 0.1 μg of the compound of the present invention (an internal standard substance for analysis). Add 〜１０10 mg. The mixed solution is concentrated, diluted with a solvent as necessary, and an internal standard substance (p-terphenyl or the like can be used) is added to prepare a measurement sample. The amount of the styrene trimer and the recovery of the compound of the present invention added are quantified by GC-MS or LC-MS.

A correction calculation was performed according to the equation (elution amount of styrene trimer from polystyrene container) = (quantification result of styrene trimer) / (recovery ratio of surrogate compound), and the true value of the elution amount of styrene trimer from the polystyrene container was calculated. Get the value.

The measurement sample referred to herein is EPS (expa
ndable polystyrene) beads, PS
P (polystyrene paper) resin, H
IPS (high impact polystyle)
ne) Resin, EPS (expandable pol)
ystyrene) cup, PSP (polystyr)
ene paper cup, HIPS (high i)
and polystyrene products such as polystyrene buffers.

The solvent referred to herein is water, hot water, n-
Hexane, n-heptane, n-pentane, cyclohexane, methanol, ethanol, 1-propanol, 2-
Examples thereof include propanol, acetonitrile, and a mixed solvent thereof.

The mixed solution may be concentrated to dryness under normal pressure, to dryness under reduced pressure, to dryness by a stream of nitrogen, argon, air, or the like.
A method of concentrating to 10 mL, and the like can be mentioned.

The diluting solvent used here includes n-hexane, n-heptane, n-pentane, cyclohexane, methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, chloroform, methylene chloride, and mixed solvents thereof. Can be

<Quantitative method 3> Food in polystyrene container
A method for quantifying the amount of styrene trimer eluted into an instant noodle in a polystyrene container will be described below as an example.If the food in the polystyrene container is a liquid food such as a soup, the operation of homogenizing the content into a paste is described. No need.

Water to boiling water is poured to one measurement sample up to the waterline, and the sample is brought into contact at room temperature to 100 ° C. for 10 minutes to 100 hours.
Paste the contents with a homogenizer etc., 0.1g
１００100 g is measured and used as a quantitative test solution (a solution obtained by diluting a paste-like solution or a concentrated solution can be used as a quantitative test solution), and the compound of the present invention (an internal standard substance for analysis) is added thereto. 0.1 ng to 10 mg are added. After adding 1 mL to 100 mL of the solvent to permeate, centrifuge. After collecting a liquid layer and performing an extraction operation, the organic layer is concentrated. After performing the cleanup operation, the solvent is diluted as necessary, and an internal standard substance (p-terphenyl or the like can be used) is added to obtain a measurement sample. The amount of the styrene trimer and the recovery of the compound of the present invention added are quantified by GC-MS or LC-MS.

(Transfer amount of styrene trimer in food in food form) = (Quantitative result of styrene trimer) マ ー
Correction calculation is performed using the formula (addition and recovery rate of surrogate compound) to obtain a true value of the transfer amount of the styrene trimer in the meal form.

The measurement sample referred to herein is EPS (expa
Foods in ndable polystyrene container, food in PSP (polystyrene paper) container, HIPS (high impact po)
lysylene) in a container, such as instant noodles in cups, instant cooked rice in cups, miso soup, soup, and juice in cups.

The solvent mentioned here includes methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, a mixed solvent thereof and the like. Also,
Solvents used in the extraction operation of this test method include n-hexane, n-heptane, cyclohexane, diethyl ether, and a mixed solvent thereof.

The clean-up operation means that the concentrated solution is once adsorbed on an adsorbent such as silica gel, celite, florisil, activated carbon, and the like, and diethyl ether, tetrahydrofuran, methanol, ethanol, 1-propanol, 2-propanol,
This shows an operation of solid-phase extraction of a measurement solution with propanol, acetonitrile, n-hexane, n-heptane, cyclohexane, chloroform, dichloromethane, and a mixed solvent thereof.

The mixed solution may be concentrated to dryness under normal pressure, dried under reduced pressure, dried by a stream of nitrogen, argon, air, or the like.
A method of concentrating to 10 mL, and the like can be mentioned.

The diluting solvents used here are n-hexane, n-heptane, n-pentane, cyclohexane, methanol, ethanol, 1-propanol, 2-
Examples thereof include propanol, acetonitrile, chloroform, dichloromethane, and a mixed solvent thereof.

The production examples and test examples of the present invention will be described more specifically below with reference to examples. Note that, in ¹³ C-NMR, the peak intensity of a ¹³ C atom to which a deuterium atom is bonded is significantly reduced as compared with a non-deuterated compound, and the peak of a ¹³ C atom to which one deuterium atom is bonded is equivalent. It becomes even smaller due to splitting into three peaks. Most of the compounds described in the following production examples have a hydrogen atom on the benzene ring replaced with a deuterium atom, and the peak of the ¹³ C atom is concentrated as a small peak split around 125 to 135 ppm. Analysis becomes extremely difficult. Therefore, in order to avoid credibility and confusion as compound data, ^13C
-The NMR data described only the peak of the carbon atom to which no deuterium atom was bonded.

[0178]

EXAMPLES Production Example 1) 1-phenyl -d _5-1-(tri
Methylsiloxy) ethylene (1-phenyl-1- (trimethylsiloxy) ethylene -d ₅₎ Process Under a nitrogen atmosphere, diisopropylamine (4.86 g,
1.2 eq. ) Of anhydrous tetrahydrofuran (60 mL)
The solution was cooled to 0 ° C., and 1.54 M n-butyllithium (n-hexane solution) (44.0 mL, 1.1e) was added thereto.
q. ) Was added dropwise, and the mixture was further stirred at 0 ° C. for 30 minutes. This was cooled to −78 ° C., and anhydrous tetrahydrofuran (15 m
Acetophenone -d ₅ dissolved in L) (Ph-d ₅₎
(5.0 g, 40.0 mmol) was added dropwise.
Stirred at 8 ° C. for 30 minutes. At −78 ° C.,
Chlorotrimethylsilane (8.63 mL, 1.7e
q. ) Was added and the mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The precipitated powder was filtered through Celite (n- hexane) was, 2 mmHg subjected to vacuum distillation, 50-52 as a fraction of ° C. 1-phenyl -d _{5-1-(trimethylsiloxy)}
3.49 g (44%) of ethylene was obtained as a colorless oil.

[0179] 1-phenyl -d _{5-1-(Torimechirushi}
Roxy) ethylene ¹ H-NMR (CDCL ₃ , TMS) δ: 4.46 (d, 1 H, J = 2.0 Hz), 4.94
(D, 1H, J = 2.0 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 0.173 × _3, 91.0, 137.3, 155.
5. Boiling point 50-52 ° C (2 mmHg).

Production Example 2)3-hydroxy-1,3,5-
Triphenyl -d ₁₅ -1-pentanone-5-d ₁ (3-
Hydroxy-1,3,5-triphenyl-1-pentano
N-d₁₆1,3-diphenyl-d_Ten-Propene-3-d₁(1,
3-diphenylpropene-d₁₁) (500 mg, 2.2)
6 mmol) in methylene chloride (10 mL).
Cooled to ° C. Titanium chloride (IV) (322 μL,
1.3 eq. ) Was added dropwise, and the mixture was further stirred at 0 ° C. for 5 minutes.
Was. The previously synthesized 1-phenyl-d _Five-1- (g
Limethylsiloxy) ethylene (579 mg, 1.3e
q. ) And stirred at room temperature for 1 hour. Water to the reaction solution
After stopping the reaction, the organic layer was extracted with chloroform.
And washed with water. After drying over anhydrous sodium sulfate,
After concentration under reduced pressure, silica gel chromatography (n-hexane
San: ethyl acetate = 30: 1)
Xy-1,3,5-triphenyl-d_Fifteen-1-pentano
N-5-d₁554 mg (71%) as a white powder
Was.

3-Hydroxy-1,3,5-triphenyl
Le -d _{15-1-pentanone ^{-5-d 1 1 H-NMR}} (CDCL 3, TMS) δ: 2.08-2.14 (m, 1H), 2.21-2.
27 (m, 1H), 2.31-2.33, 2.74-
2.76 (m, 1H), 3.03 (d, 1H, J = 1
7.1 Hz), 3.78 (d, 1H, J = 17.1H)
z), 5.02 (s. 1H). ¹³ C-NMR (CDCL ₃ ) δ: 45.1, 48.0, 75.7, 136.7, 14
2.0, 145.4, 201.4. 80-82 ° C.

Production Example 3)1,3,5-triphenyl-d
₁₅ -1-pentanone-5-d ₁ (1,3,5-Triphe
Nil-1-pentanone-d₁₆3-hydroxy-1,3,5-triphenyl-d_Fifteen-1
-Pentanone-5-d ₁(400mg, 1.16mmo
l) was dissolved in chloroform (7 mL),
(469 μL, 5.0 eq.) And cooled to 0 ° C.
Was. Thionyl chloride (169 μl) was added to the reaction solution.
L, 2.0 eq. ) And stirred at room temperature for another hour
did. After the reaction solution was concentrated under reduced pressure, the organic layer was separated into chloroform.
Extract, wash with water and dry with anhydrous sodium sulfate
did. By concentrating under reduced pressure, 3-chloro-1,3,5
-Triphenyl-d_Fifteen-1-pentanone-5-d₁Coarse
The product was obtained.

[0183] destination yield, dissolved 3-chloro-1,3,5-triphenyl -d _15-1-crude pentanone -5-d ₁ and N, N-dimethylformamide (7 mL),
To this, sodium iodide (522 mg, 3.0 eq.)
Was added and stirred at 100 ° C. for 1 hour. The organic layer was extracted with toluene, washed with brine, and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (n-hexane: ethyl acetate = 30: 1) to give 3-hydroxy-1,3,5-triphenyl-d _15.
-1- 348mg (92%) of the dehydrated product pentanone -5-d ₁ as an isomer mixture was obtained.

3-Hydroxy-1,3,5-triphenyl
Ru-d_Fifteen-1-pentanone-5-d ₁Dehydration products
Isomer mixture (330mg, 1.0mmol)
Dissolved in ethyl (6 mL) and added with a catalytic amount of 10% Pd.
-C (20 mg) was added and the mixture was violently at room temperature under a hydrogen atmosphere.
Stir for 5 hours. After filtration through celite (ethyl acetate), the mother
The solution is concentrated and the resulting crude product is chromatographed on silica gel.
Raffy (n-hexane: ethyl acetate = 30: 1)
Purified, 1,3,5-triphenyl-d_Fifteen-1-penta
Non-5-d₁220 mg (66%) as white powder
Obtained.

[0185] 1,3,5 -d _15-1-Bae
Ntanon ^{_{-5-d 1 1 H-NMR}} (CDCL 3, TMS) δ: 1.93-1.99 (m, 1H), 2.08-2.
09 (m, 1H), 2.42-2.50 (m, 1H),
3.22-3.29 (m, 2H), 3.33-3.42
(M, 1H). ¹³ C-NMR (CDCL ₃ ) δ: 37.7, 40.9, 46.0, 136.8, 14
1.7, 144.0, 198.7. 79-81 ° C.

Production Example 4) 2,4,6-Triphenyl-d
₁₅ 1-hexene -6-d ₁ preparation triphenylphosphonium bromide (2,4,6-phenyl-1-hexene -d ₁₆₎ (974m
g, 5.0 eq. ) In anhydrous diethyl ether (15 m
L) 1.54M n-butyllithium (n-hexane solution) (1.77 mL,
5.0 eq. ) Was added dropwise and stirred at room temperature for 30 minutes. 1,3,5 dissolved in a mixed solution of anhydrous tetrahydrofuran (5 mL) and anhydrous diethyl ether (5 mL)
- triphenyl -d _{15-1-pentanone} -5-d _{1 (1}
80 mg, 0.545 mmol) was added dropwise. 1 at room temperature
After stirring for an hour, n-hexane (100 m
L) was added, and the precipitated powder was filtered through celite (n-hexane). The mother liquor was concentrated under reduced pressure, the resulting crude product was purified by silica gel chromatography (n- hexane), 2,4,6-triphenyl -d _15-1-hexene -
The 6-d ₁ was obtained 143 mg (80%) as a colorless oil.

2,4,6-triphenyl-d ₁₅ -1-f
Cyclohexene ^{_{-6-d 1 1 H-NMR}} (CDCL 3, TMS) δ: 1.80-1.86 (m, 1H), 1,92-2.
03 (m, 1H), 2.24-2.39 (m, 1H),
2.60-2.69 (m, 1H), 2.70-2.82
(M, 2H), 4.84 (s, 1H), 5.11 (s,
1H). ¹³ C-NMR (CDCL ₃ ) δ: 37.3, 43.4, 43.5, 114.3, 14
0.8, 142.1, 144.7, 146.5. Mass EI method: 328 (M ⁺ ).

Production Example 5 1,3-Diphenyl-d ₁₀ -2
- propen-1-one preparation benzaldehyde -d ₅ of (chalcone -d ₁₀₎ (4.4g, 40.0mmo
l) and acetophenone _{-d 5 (Ph-d 5)} (5.0
g, 1.0 eq. ) Suspension in water (30 mL) was stirred at room temperature, 2N sodium hydroxide in methanol solution (26.0 mL, 1.3 eq.) Was added, and the mixture was stirred at room temperature for 4 hours. The organic layer was extracted with toluene, washed with brine, and dried over anhydrous sodium sulfate. After concentration under reduced pressure, 6.69g (77%) precipitated crystals of 1,3-diphenyl -d _{10-2-propen-1-one} by washing with n- hexane as pale yellow crystals were obtained.

[0189] 1,3-diphenyl -d ₁₀ -2- propene
-1-one ¹ H-NMR (CDCL ₃ , TMS) δ: 7.53 (d, 1 H, J = 15.6 Hz), 7.8
1 (d, 1H, J = 15.6 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 122.0, 134.6, 137.9, 144.
6, 190.4. 55-57 ° C.

Production Example 6 2-chloroacetophenone-d
₅ (Ph-d ₅₎ of the manufacturing method of aluminum chloride (35.0 g, 1.1 eq.) Of chloroacetyl chloride in chloroform solution (100 mL) of (2
1.0 mL, 1.1 eq. ), And benzene-d ₆ (20.0 g, 238 mmol) was added dropwise thereto at 0 ° C.
It was left at room temperature for 30 minutes. Cool the reaction to 0 ° C and add 1N
An aqueous hydrochloric acid solution was added to stop the reaction, the organic layer was extracted with chloroform, washed with saturated saline, and dried over anhydrous sodium sulfate. After concentration under reduced pressure to give 35.1 g (92%) crystallized by n- hexane was carried out 2-chloroacetophenone -d ₅ (Ph-d ₅₎ as white crystals.

2-Chloroacetophenone-d ₅ (Ph-
d ₅ ) ¹ H-NMR (CDCL ₃ , TMS) δ: 4.72 (s, 2H). ¹³ C-NMR (CDCL ₃ ) δ: 46.1, 133.9, 190.8. Mass EI method: 160, 162 (M ⁺ ). 54-56 ° C.

Production Example 7) 2-chloroethylbenzene-d
₅ (Ph-d ₅₎ of the preparation of 2-chloro acetophenone _{-d 5 (Ph-d 5)} (35.
1 g, 219 mmol) in trifluoroacetic acid (88
mL) in triethylsilane (79 mL, 2.3 eq.)
Was added and heated under reflux for 36 hours. After concentrating the reaction solution under reduced pressure,
The organic layer was extracted with chloroform, washed with saturated aqueous sodium hydrogen carbonate, and dried over anhydrous sodium sulfate. Was purified by vacuum distillation and silica gel column chromatography (n- hexane), 2-chloro-benzene -d ₅ (Ph-
d ₅₎ to give 5.8 g (18%) as a colorless oil.

Chloroethylbenzene -d ₅ (Ph-d ₅ ) ¹ H-NMR (CDCL ₃ , TMS) δ: 3.07 (t, 2H, J = 7.2 Hz), 3.72
(T, 2H, J = 7.2 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 39.1, 44.9, 137.8. Boiling point 82-84 ° C (16 mmHg).

Production Example 8) 1,3,5-Triphenyl-d
₁₅ 1-pentanone preparation nitrogen atmosphere, magnesium (342 mg, 1.3E
q. ) In anhydrous diethyl ether solution (44 mL)
Chloro-ethylbenzene -d ₅ (1.90g, 1.2e
q. ) And heated under reflux for 3 hours. After cooling the reaction solution to room temperature, chalcone-d ₁₀ (2.4 g, 11.0 mmol)
l) An anhydrous tetrahydrofuran solution (22 mL) was added, and the mixture was stirred at room temperature for 1 hour. The reaction was cooled to 0 ° C. and
The reaction was stopped by adding an aqueous solution of N hydrochloric acid. The organic layer was extracted with chloroform, washed with saturated saline, and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (n-hexane: ethyl acetate = 20: 1) and recrystallized from methanol to give 1,3,3.
5-triphenyl -d _{15-1-pentanone} was obtained 1.01 g (28%) as a white powder.

1,3,5-triphenyl-d ₁₅ -1-pe
Tanthanone ¹ H-NMR (CDCL ₃ , TMS) δ: 1.90-2.01 (m, 1H), 2.04-2.
13 (m, 1H), 2.43-2.55 (m, 2H),
3.22-3.32 (m, 2H), 3.35-3.44
(M, 1H). ¹³ C-NMR (CDCL ₃ ) δ: 33.7, 37.9, 41.0, 46.0, ¹³
6.9, 141.8, 144.1, 198.7. 79-81 ° C.

The following compounds were produced in the same manner as in Production Example 4 using 1,3,5-triphenyl-d ₁₅ -1-pentanone as a starting material.

Production Example 9) 2,4,6-Triphenyl-d
₁₅ 1-hexene _{^{1 H-NMR (CDCL 3,}} TMS) δ: 1.82-1.93 (m, 1H), 1.99-2.
10 (m, 1H), 2.30-2.47 (m, 2H),
2.64-2.73 (m, 1H), 2.76-2.88
(M, 2H), 4.89 (s, 1H), 5.15 (s,
1H). ¹³ C-NMR (CDCL ₃ ) δ: 33.6, 37.3, 43.4, 43.6, 11
4.3, 140.8, 142.1, 144.7, 14
6.5. Mass EI method: 327 (M ⁺ ).

Production Example 10)Ethyl-phenyl -d ₅
-2-propenate-3-d ₁ (Ethyl cinnamate-
d₆) Preparation of sodium hydride (2.14 g, 1.2 eq.)
The ene (40 mL) suspension was cooled to 0 ° C.
Drop of triethyl monoacetate (10.6 mL, 1.2 eq.)
Then, the mixture was further stirred at room temperature for 10 minutes. This reaction solution
Benzaldehyde dissolved in toluene (10 mL)
-D₆(5.0 g, 44.6 mmol) for 2 hours
Heated to reflux. Water was added to the reaction solution to stop the reaction
After that, the organic layer was extracted with toluene, washed with saturated saline,
It was dried over anhydrous sodium sulfate. After concentration under reduced pressure,
Kagel chromatography (n-hexane: ethyl acetate
= 10: 1) and purified by ethyl-3-phenyl-d_Five
-2-propenate-3-d₁As a colorless oil
7.35 g (91%) were obtained.

[0199] Ethyl-3-phenyl -d _5-2-propenyl
Sulfonates ^{_{-3-d 1 1 H-NMR}} (CDCL 3, TMS) δ: 1.33 (t, 3H, J = 7.3Hz), 4.25
(D, 2H, J = 7.3 Hz), 6.42 (d, 2H,
J = 2.0 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 14.3, 60.4, 118.0, 134.1, 1
66.7.

[0200] Production Example 11) 3- phenyl -d _5-2-flops
Ropen -1- preparation of ethyl-ol -3-d ₁ (cinnamyl alcohol -d ₆₎ -3-phenyl--d _{5-2-Puropeneto} 3-
d ₁ (5.0 g, 27.5 mmol) was added to toluene (30
mL) and cooled to 0 ° C. 1.1
M diisobutylaluminum hydride (toluene solution) (54.9 mL, 2.2 eq.) Was added, and the mixture was heated under reflux for 1.5 hours. After cooling the reaction solution to 0 ° C., a 2N aqueous hydrochloric acid solution was added to stop the reaction. The organic layer was extracted with ethyl acetate, washed with brine, and dried over anhydrous sodium sulfate. After concentration under reduced pressure, silica gel column chromatography (n- hexane: ethyl acetate = 5: 1 to 3: 1) to give 3-phenyl -d _{5-2-propen-1-white} ol -3-d ₁ 2.66 g (69%) were obtained as a powder.

[0201] 3-phenyl -d _5-2-propen-1
All ^{_{-3-d 1 1 H-NMR}} (CDCL 3, TMS) δ: 4.27-4.28 (m, 2H), 6.30-6.
32 (m, 1H). ¹³ C-NMR (CDCL ₃ ) δ: 63.4, 128.2, 136.3. 33-35 ° C.

Production Example 12) 1-Bromo-3-phenyl-
d _5-2-propene -3-d ₁ (cinnamyl bromide -d
₆₎ the preparation of 3-phenyl--d _{5-2-propen-1-ol-3}
d ₁ a (210 mg, 1.5 mmol) was dissolved in methylene chloride (5 mL), which triphenylphosphine (433mg, 1.1eq.), N- bromosuccinimide (294 mg, 1.1 eq.) were sequentially added at room temperature For 30 minutes. Add n-hexane (50 mL),
After diluting the reaction solution, the resulting precipitate was filtered through celite (n-hexane), and the mother liquor was concentrated under reduced pressure to give 1-bromo-
350mg of 3-phenyl--d _5-2-propene -3-d ₁ as an oil (quant.) Was obtained. ¹ H-NMR (CDCL ₃ , TMS) δ: 4.14 (d, 2H, J = 7.3 Hz), 6.36
(T, 1H, J = 7.3 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 33.4, 124.9, 135.4.

[0203] Production Example 13) Benzyl -d ₅ - Feniruke
Ton (ring -d ₅₎ Process Under a nitrogen atmosphere (benzyl phenyl ketone -d _5), magnesium (283 mg, 1.2e
q. Anhydrous diethyl ether solution (8 mL) benzyl bromide -d ₇ (2.07 g of), 1.2 eq.) Was added and stirred for 30 minutes at room temperature. To this was added a solution of benzonitrile (1.0 g, 9.7 mmol) in anhydrous diethyl ether (2 mL), and the mixture was heated under reflux for 2 hours. The reaction solution was cooled to 0 ° C., and a 2N aqueous hydrochloric acid solution was added to stop the reaction.
The organic layer was extracted with ethyl acetate, washed with saturated saline,
It was dried over anhydrous sodium sulfate. After concentration under reduced pressure, purification was performed by silica gel column chromatography (n-hexane: ethyl acetate = 20: 1).

The obtained compound was dissolved in methanol (10 mL).
And tetrahydrofuran (10 mL), and 28% sodium methylate (methanol solution) (5 m
L) was added and the mixture was stirred at 0 ° C. for 1 hour. 2N in the reaction solution
An aqueous hydrochloric acid solution was added to stop the reaction, and the organic layer was extracted with ethyl acetate, washed with saturated saline, and dried over anhydrous sodium sulfate. The crystals precipitated by concentration under reduced pressure are n-
Benzyl -d ₅ by washing with hexane - 881 mg (4 phenyl ketone (ring -d ₅₎ as a white powder
5%).

[0205] Benzyl -d ₅ - phenyl ketone (ring -
d ₅ ) ¹ H-NMR (CDCL ₃ , TMS) δ: 4.28 (s, 2H), 7.44 (t, 2H, J =
7.3 Hz), 7.52-7.56 (m, 1H), 8.
00 (dd, 2H, J = 1.5, 7.3 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 45.4, 128.5 × 4, 133.0, 134.
2,136.5,197.4. 55-57 ° C.

Production Example 14) 1S ^* -benzoyl-4S ^* -
Phenyl -d ₅ - tetralin -4,5,6,7,8-d ₅
(1S ^* -benzoyl-4S ^* -phenyltetralin-d
_10), 1R ^* - benzoyl -4S ^* - phenyl -d ₅ - Te
Torarin -4,5,6,7,8-d ₅ (1R ^* - benzoyl -4S ^* - phenyl tetraline -d ₁₀₎ preparation of sodium hydride (. 358mg, 1.2eq) and n-
After washing with hexane, N, N-dimethylformamide (15 mL) was added under a nitrogen atmosphere to form a suspension.
This was stirred while cooling to 0 ° C., and benzylphenylketone-d ₅ (1.50 g, 7.46 mmol) dissolved in N, N-dimethylformamide (3 mL) was added dropwise thereto. After the completion of hydrogen bubbling, the mixture was further stirred at room temperature for 30 minutes. To this, N, N-dimethylformamide (2 m
L) dissolved in cinnamyl bromide-d ₆ (2.28
g, 1.5 eq. ) Was added dropwise and stirred at room temperature for 1.5 hours. After adding water to the reaction solution to stop the reaction, the organic layer was extracted with toluene and washed with saturated saline. After drying over anhydrous sodium sulfate, the mixture was concentrated under reduced pressure to give 2,5-diphenyl-
d ₁₀ 1-phenyl-4-penten-1-one -5-d
A crude product of ₁ was obtained.

The previously obtained 2,5-diphenyl-d ₁₀ -1-
Phenyl-4-penten-1-one -5-d ₁ of the crude product in toluene (80 mL) was added P- toluenesulfonic acid (3.12 g, 2.0 eq.) And the silica gel (3.98 g) was added The mixture was heated under reflux for 3.5 hours. After the precipitate was separated by filtration (ethyl acetate), the solvent was concentrated under reduced pressure by about 80%, and the organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated saline solution. After drying over anhydrous sodium sulfate,
Concentrated in vacuo, and purified by silica gel chromatography (n- hexane: ethyl acetate = 20: 1) to obtain, 1.93 g (53%) of 1-benzoyl-4-phenyl tetralin -d ₁₀ as a white powder was obtained.

[0208] 1-benzoyl-4-phenyl tetralin -d ₁₀ was further purified by silica gel chromatography (n-
Hexane: toluene: ethyl acetate = 25: 25: 1) to give 1S ^* -benzoyl-4S ^* -phenyl-d as a white powder.
₅ - tetralin -4,5,6,7,8-d ₅ and, as a white powder 1R ^* - benzoyl -4S ^* - separated tetralin -4,5,6,7,8-d ₅ - phenyl -d ₅ did.

1S ^* -benzoyl-4S ^* -phenyl-d
₅ - tetralin ^{_{-4,5,6,7,8-d 5 1 H-NMR}} (CDCL 3) δ: 1.84-1.92 (m, 1H), 1.98-2.
10 (m, 1H), 2.20-2.32 (m, 2H),
4.97 (dd, 1H, J = 6.3, 6.3 Hz),
7.49 (d, 2H, J = 7.3 Hz), 7.57-
7.61 (m, 1H), 8.03 (d, 2H, J = 7.
3 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 25.1, 30.3, 47.4, 128.7 × 4.
133.0, 135.1, 136.5, 139.7, 1
46.5, 202.3. 104-106 ° C.

1R ^* -benzoyl-4S ^* -phenyl-d
₅ - tetralin ^{_{-4,5,6,7,8-d 5 1 H-NMR}} (CDCL 3) δ: 1.97-2.02 (m, 1H), 2.06-2.
11 (m, 1H), 2.11 to 2.19 (m, 2H),
4.96 (dd, 1H, J = 5.9, 5.9 Hz),
7.51 (d, 2H, J = 7.3 Hz), 7.56 (d
d, 1H, J = 1.5, 7.3 Hz), 8.07 (d
d, 2H, J = 1.5, 7.3 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 25.6, 29.8, 47.0, 128.5 × 2
128.6 × 2, 132.9, 135.0, 136.
4,140.3,146.5,201.9. Melting point 101-103 ° C.

Production Example 15) 1S ^* -Phenyl -d ₅ -4R
^* -(1-phenylethenyl) tetralin-1,5,
6,7,8-d ₅ (1S ^* - phenyl -4R ^* - (1-phenylethenyl) tetralin -d ₁₀₎ preparation of 1S ^* - benzoyl -4S ^* - phenyl tetraline -d ₁₀
(300 mg, 0.93 mmol) in anhydrous diethyl ether (3 mL) was stirred at room temperature, and 3.0M methylmagnesium bromide (diethyl ether solution) was added thereto.
(464 μL, 1.5 eq.) Was added dropwise. After heating at reflux for 30 minutes, the reaction solution was cooled to 0 ° C.
The reaction was stopped by dropwise addition of aqueous hydrochloric acid. The organic layer was extracted with ethyl acetate, washed with brine, and dried over anhydrous sodium sulfate. Concentrated under reduced pressure, 1- (1-hydroxy-1-phenylethyl) -4-phenyl -d ₅ -
Tetralin -4,5,6,7,8-d ₅ was obtained as a crude product.

[0212] destination obtained 1- (1-hydroxy-1-phenylethyl) -4-phenyl -d ₅ - tetralin -4,
Chloroform crude 5,6,7,8-d ₅ (3m
L) Add methanesulfonyl chloride (143 μL,
2eq. ) And heated under reflux for 3 hours. 4N in ice bath
After neutralization with an aqueous sodium hydroxide solution, the mixture was extracted with ethyl acetate and washed with saturated saline. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified by silica gel chromatography (n-hexane).
S ^* - phenyl -d ₅ -4R ^* - (1- phenylethenyl) 243 g of tetralin -1,5,6,7,8-d ₅ as a white powder (81%).

1S ^* -Phenyl -d ₅ -4R ^* -(1-F
Enylethenyl) tetralin-1,5,6,7,8-d
_{^{5 1 H-NMR (CDCL 3}} ) δ: 1.61-1.67 (m, 1H), 1.72-1.
78 (m, 1H), 1.92-1.99 (m, 1H),
2.18-2.26 (m, 1H), 4.20 (dd, 1
H, J = 5.9, 5.9 Hz), 4.76 (s, 1
H), 5.41 (s, 1H), 7.20-7.29.
(M, 3H), 7.35 (dd, 2H, J = 1.5,
6.8 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 25.6, 29.7, 44.9, 116.2, 12
6.7 × 2, 127.2, 128.2 × 2, 138.
8, 139.4, 141.6, 147.2, 153.
1. 72-74 ° C.

1R ^* -benzoyl-4S ^* -phenyl-d
_The following compound was produced in the same manner as in Production Example 15 using ₅ -tetralin-4,5,6,7,8-d5 as a starting material.

Production Example 16) 1S ^* -phenyl-d ₅ -4S
^* -(1-phenylethenyl) tetralin-1,5,
6,7,8-d ₅ (1S ^* - phenyl -4S ^* - (1- phenylethenyl) tetralin ^{_{-d 10) 1 H-NMR (}} CDCL 3) δ: 1.76-1.79 (m, 1H ), 1.84-1.
94 (m, 2H), 4.17-4.19 (m, 1H),
4.74 (s, 1H), 5.44 (s, 1H), 7.2
3-7.32 (m, 3H), 7.40-7.43 (m,
2H). ¹³ C-NMR (CDCL ₃ ) δ: 26.2, 29.2, 44.3, 117.0, 12
6.7 × 2, 127.3, 128.2 × 2, 138.
4, 140.2, 141.8, 147.1, 153.
9. 47-53 ° C.

Production Example 17) 1S ^* -phenyl-d ₅ -4R
^* -(1S ^* -phenylethyl) tetralin-1,5,
6,7,8-d ₅ (1S ^* - phenyl -4R ^* - (1S ^* -
Phenylethyl) tetralin -d _10), 1S ^* - phenylene
Le _{^{-d 5 -4R * - (1R *}} - phenylethyl) Tetorari
-1,5,6,7,8-d ₅ (1S ^* -phenyl-4R
^* - (1R ^* - phenylethyl) preparation of tetralin -d ₁₀₎ 1S ^* - phenyl -4R ^* - (1-phenylethenyl) tetralin -d ₁₀ (565mg, 1.77mmol) in ethyl acetate (5 mL) Dissolve and add 10% Pd / C
(56 mg) and stirred vigorously at room temperature under a hydrogen atmosphere for 3 hours. After filtration through celite (ethyl acetate), the mother liquor was concentrated under reduced pressure, and the obtained crude product was purified by silica gel chromatography (n-hexane) to give 1S ^* -phenyl-
d ₅ -4R ^* - (1- phenylethyl) tetralin -1,
538mg of 5, 6, 7, 8-d ₅ as a colorless oil
(94%).

1S ^* -phenyl-d ₅ -4R ^* -(1-phenylethyl) tetralin-1,5,6,7,8-d ₅
To high performance liquid chromatography (TSKgel)
ODS-80TSQA, 90% methanol, 10% water)
At a white powder 1S ^* - phenyl -d ₅ -4R ^* - (1S ^*
-Phenylethyl) tetralin-1,5,6,7,8-
d ₅ and, as a white powder 1S ^* - phenyl -d ₅ -4R ^* -
(1R ^* -phenylethyl) tetralin-1,5,6
It was separated into 7,8-d _5.

1S ^* -phenyl-d ₅ -4R ^* -(1S ^* -
Phenylethyl) tetralin-1,5,6,7,8-d
_{^{5 1 H-NMR (CDCL 3}} ) δ: 1.32 (d, 3H, J = 6.8Hz), 1.44
−1.51 (m, 1H), 1.57-1.64 (m, 1
H), 1.73-1.84 (m, 1H), 2.07-
2.14 (m, 1H), 3.09-3.20 (m, 2
H), 7.12 (dd, 2H, J = 1.5, 6.8H)
z), 7.15-7.21 (m, 1H), 7.21-
7.29 (m, 2H). ¹³ C-NMR (CDCL ₃ ) δ: 20.8, 22.0, 28.7, 44.1, 44.
3,125.9,127.6 × 2,128.1 × 2,1
39.7, 139.9, 145.5, 147.5. Mass CI method: 323 (M + H) ⁺ . Melting point 56-57 [deg.] C.

1S ^* -phenyl-d ₅ -4R ^* -(1R ^* -
Phenylethyl) tetralin-1,5,6,7,8-d
_{^{5 1 H-NMR (CDCL 3}} ) δ: 1.15 (d, 3H, J = 6.8Hz), 1.52
-1.62 (m, 2H), 1.65-1.77 (m, 2
H), 2.08-2.18 (m, 1H), 3.21-
3.29 (m, 1H), 3.53-3.62 (m, 1
H), 7.19-7.36 (m, 5H). ¹³ C-NMR (CDCL ₃ ) δ: 13.8, 22.2, 31.7, 42.7, 44.
5,125.9,127.9 × 2,128.0 × 2,1
39.4, 140.8, 145.5, 147.0. Mass CI method: 323 (M + H) ⁺ . 92-94 ° C.

Production Example 18) 1S ^* -phenyl-d ₅ -4S
^* -(1R ^* -phenylethyl) tetralin-1,5,
6,7,8-d ₅ (1S ^* - phenyl -4S ^* - (1R ^* -
Phenylethyl) tetralin -d _10), 1S ^* - phenylene
Le _{^{-d 5 -4S * - (1S *}} - phenylethyl) Tetorari
-1,5,6,7,8-d ₅ (1S ^* -phenyl-4S
^* - preparation of - (1S ^* phenylethyl) tetralin -d ₁₀₎

1S ^* -phenyl-d ₅ -4S ^* -(1-phenylethenyl) tetralin-1,5,6,7,8-d
_The following compounds were produced in the same manner as in Production Example 17 using ₅ as a starting material.

1S ^* -phenyl-d ₅ -4S ^* -(1R ^* -
Phenylethyl) tetralin-1,5,6,7,8-d
_{^{5 1 H-NMR (CDCL 3}} ) δ: 1.38 (d, 3H, J = 6.8Hz), 1.57
-1.65 (m, 1H), 1.65-1.75 (m, 1
H), 1.78-1.93 (m, 2H), 2.99-
3.05 (m, 1H), 3.18-3.27 (m, 1
H), 7.14-7.21 (m, 3H), 7.21-
7.28 (m, 2H). ¹³ C-NMR (CDCL ₃ ) δ: 21.2, 24.3, 29.4, 44.3, 44.
5,125.9,127.7 × 2,128.2 × 2,1
39.6, 139.7, 145.5, 147.5. Mass CI method: 323 (M + H) ⁺ . 104-106 ° C.

1S ^* -phenyl-d ₅ -4S ^* -(1S ^* -
Phenylethyl) tetralin-1,5,6,7,8-d
_{^{5 1 H-NMR (CDCL 3}} ) δ: 1.24 (d, 2H, J = 7.3Hz), 1.40
-1.49 (m, 1H), 1.78-1.88 (m, 1
H), 1.90-2.08 (m, 2H), 3.02-
3.10 (m, 1H), 3.44-3.52 (m, 1
H), 7.18-7.22 (m, 3H), 7.22-
7.30 (m, 2H). ¹³ C-NMR (CDCL ₃ ) δ: 15.4, 21.0, 30.0, 43.2, 44.
8, 125.9, 128.0 × 4, 139.1, 13
9.9, 145.7, 147.3. Mass CI method: 323 (M + H) ⁺ . Melting point 119-122 [deg.] C.

Production Example 19) Ethyl-3,3-diphenyl
-D _{10-2-Puropeneto} (ethyl-3-phenyl cinnamic mate -d ₁₀₎ preparation of sodium hydride (4.4 g, 1.1 eq.) In toluene (200 mL) suspension triethyl phosphonoacetate (2
4.6 g, 1.1 eq. ) And stirred at room temperature for 30 minutes. In this reaction solution, benzophenone-d ₁₀ (ring-d ₁₀ ) (19.2 g,
0.1 mol) and heated under reflux for 4 hours. After water was added to the reaction solution to stop the reaction, the organic layer was extracted with toluene, washed with saturated saline, and dried over anhydrous sodium sulfate. After concentration under reduced pressure, purified by silica gel chromatography (toluene: n-hexane = 1: 1) to obtain, 19.9 g (79%) of ethyl 3,3-diphenyl -d _{10-2-Puropeneto} as a colorless oil Obtained.

Ethyl-3,3-diphenyl-d ₁₀ -2-
Propenate ¹ H-NMR (CDCL ₃ , TMS) δ: 1.11 (t, 3H, J = 7.2 Hz), 4.04
(Q, 2H, J = 7.2 Hz), 6.37 (s, 1
H). ¹³ C-NMR (CDCL ₃ ) δ: 14.0, 60.0, 117, _3, 138.7, 1
40.5, 156.2, 166.0. Mass EI method: 252 (M ⁺ ).

[0226] Production Example 20) 3,3-diphenyl -d ₁₀ -
Pro Pearl preparation of ethyl-3-phenyl cinnamate -d ₁₀ (19.9
g, 79 mmol) in n-hexane (200 mL), 10% Pd-C (1.0 g) was added thereto, and the mixture was vigorously stirred at room temperature under a hydrogen atmosphere for 2 hours. Celite filtration
After (ethyl acetate), the mother liquor was concentrated under reduced pressure to give ethyl-3,3.
- to obtain a crude product of propionate - diphenyl -d _10.

Ethyl-3,3-diphenyl- obtained above
The crude product of d ₁₀ -propionate was dissolved in THF (200 m
L) and dissolved in lithium borohydride (9.6 g, 5.L).
6 eq. ) And heated under reflux for 3 hours. After stopping the reaction by adding water to the reaction solution, the organic layer was extracted with ethyl acetate,
After washing with an aqueous sodium hydrogen carbonate solution and saturated saline, the extract was dried over anhydrous sodium sulfate. After concentration under reduced pressure, silica gel chromatography (n-hexane: ethyl acetate =
2: 1) to give 3,3-diphenyl -d ₁₀ - 15.7 g of propanol as a colorless oil (90%) was obtained.

[0228] 3,3-Diphenyl -d ₁₀ - Pro Pearl _{^{1 H-NMR (CDCL 3,}} TMS) δ: 1.11 (dd, 2H, J = 7.8,6.4H
z), 3.60 (t, 2H, J = 6.4 Hz), 4.1
4 (t, 1H, J = 7.8 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 38.3, 47.2, 61.1, 144.2 × 2. Mass EI method: 222 (M ⁺ ).

[0229] Production Example 21) 4,4-diphenyl -d ₁₀ -
Butyric acid of Preparation 3,3-diphenyl -d ₁₀ - propanol (15.7
g, 70.7 mmol) in a mixed solution of N, N-dimethylformamide (8 mL) and chloroform (160 mL) was added with thionyl chloride (16.4 mL, 2.7 eq.), and the mixture was heated under reflux for 30 minutes. The reaction solution was concentrated under reduced pressure, the organic layer was extracted with chloroform, saturated sodium hydrogen carbonate,
Washed with saturated saline. After drying over anhydrous sodium sulfate, the mixture was concentrated under reduced pressure to give 1-chloro-3,3-diphenyl-d
A crude product of ₁₀ -propane was obtained.

To a solution of the crude product of 1-chloro-3,3-diphenyl-d ₁₀ -propane obtained above in dimethyl sulfoxide (80 mL), potassium cyanide (7.1 g, 1.1 g) was added.
5 eq. ) And a catalytic amount of potassium iodide (100 m
g) was added and the mixture was stirred at 100 ° C. for 2 hours. The organic layer was extracted with toluene and washed with saturated saline. Was obtained butyronitrile crude product - dried over anhydrous sodium sulfate, 4,4-diphenyl -d ₁₀ concentrated under reduced pressure.

To a solution of the crude product of 4,4-diphenyl-d ₁₀ -butyronitrile obtained above in ethylene glycol monomethyl ether (30 mL), potassium hydroxide (15.
6 g, 4.0 eq. ) And water (18 mL) were added, and the mixture was heated under reflux for 3 hours. The reaction solution was cooled to 0 ° C., a 2N aqueous hydrochloric acid solution was added to make the reaction solution acidic, and then the organic layer was extracted with toluene and washed with saturated saline. After drying over anhydrous sodium sulfate, and concentrated under reduced pressure, then subjected to crystallization in n- hexane, 4,4-diphenyl -d ₁₀ - 13.9g (79%) of butyric acid as a white powder was obtained.

4,4-diphenyl-d ₁₀ -butyricua
Cyd ^{1 H-NMR (10% CD} 3 OD in CDCL 3, T
MS) [delta]: 2.24-2.28 (m, 2H), 2.35-2.
40 (m, 2H), 3.95 (t, 1H, J = 8.0H)
z). ¹³ C-NMR (10% CD ₃ OD in CDCL ₃ ) δ: 30.4, 32.4, 50.2, 143.7 × 2
175.7. Mass EI method: 250 (M ⁺ ).

[0233] Production Example 22) 4-phenyl -d _5-1-Te
Tralon-5,6,7,8-d ₄ (4-phenyl-1-
Tetralone -d ₉₎ of Preparation 4,4-diphenyl -d ₁₀ - butyric acid (1
2.0 g, 48.0 mmol) of chloroform (60
(mL) solution was stirred at room temperature, and thionyl chloride (7.
5 mL, 1.8 eq. ) And heated at 60 ° C. for 1 hour. It was obtained butyryl chloride of crude product - 4,4-diphenyl -d ₁₀ by the reaction solution was concentrated under reduced pressure.

Aluminum chloride (12.8 g, 2.0e
q. ) In chloroform (600 mL) was cooled to 0 ° C., and chloroform (20 mL) of the crude product of 4,4-diphenyl-d ₁₀ -butyryl chloride obtained earlier was added thereto.
The solution was added dropwise and stirred at 0 ° C. for 1 hour. 1N in the reaction solution
After adding hydrochloric acid aqueous solution to stop the reaction, the organic layer was extracted with chloroform and washed with saturated saline. After drying over anhydrous sodium sulfate, and concentrated under reduced pressure, then subjected to crystallization in n- hexane, 4-phenyl--d _{5-1-tetralone} -5,6,7,8-d ₄ as a white powder 6. 46g
(58%).

4-phenyl-d ₅ -1-tetralone-
^{_{5,6,7,8-d 4 1 H-NMR}} (CDCL 3, TMS) δ: 2.30-2.35 (m, 1H), 2.46-2.
51 (m, 1H), 2.59-2.67 (m, 1H),
2.70-2.76 (m, 1H), 4.31 (dd, 1
H, J = 4.4 Hz, 7.8 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 31.9, 36.8, 45.2, 132, 6, 14
3.4, 146.1, 198.0. Mass EI method: 231 (M ⁺ ). 74-75 ° C.

Production Example 23) 1S ^* -phenyl-d ₅ -4S
^* - (2-phenyl -d ₅ - ethyl) tetralin -5,
6,7,8 -d ₄ (1S ^* -phenyl-4S ^* -(2-phenylethyl) tetralin-d ₁₄ ), 1S ^* -phenyl
-D ₅ -4R ^* - (2- phenyl -d ₅ - ethyl) tetra
Phosphorus-5,6,7,8-d ₄ (1S ^* -phenyl-4R ^*
- (2-phenylethyl) METHOD Under a nitrogen atmosphere tetralin -d _14), magnesium (654 mg, 1.3E
q. ) In anhydrous diethyl ether solution (84 mL).
Chloro-ethylbenzene -d ₅ (3.68g, 1.2e
q. ) And heated under reflux for 3 hours. After cooling the reaction solution to 0 ° C., 4-phenyl-1-tetralone-d ₉ (4.
(8 g, 20.8 mmol) in anhydrous tetrahydrofuran (21 mL) was added, and the mixture was stirred at room temperature for 1 hour. After the reaction solution was cooled to 0 ° C. and 1N aqueous hydrochloric acid was added to stop the reaction, the organic layer was extracted with chloroform and washed with saturated saline. After drying over anhydrous sodium sulfate, the mixture was concentrated under reduced pressure.
Purified by silica gel chromatography (n-hexane: ethyl acetate = 5: 1) and purified by 1- (1-hydroxy-2-
Phenyl -d ₅ - ethyl) -4-phenyl -d ₅ - to give a crude product of tetralin -5,6,7,8-d _4.

The crude product of 1- (1-hydroxy-2-phenyl-d ₅ -ethyl) -4-phenyl-d ₅ -tetralin-5,6,7,8-d ₄ obtained above in chloroform ( 3
Methanesulfonyl chloride (1.3 m
L, 2.0 eq. ) And heated under reflux for 2 hours. After neutralization with a 4N aqueous sodium hydroxide solution in an ice bath, the organic layer was extracted with chloroform and washed with saturated saline. After drying over anhydrous sodium sulfate, and concentrated under reduced pressure, and purified by silica gel chromatography (n- hexane), 1- (1-hydroxy-2-phenyl -d ₅ - ethyl) -4-phenyl -d ₅ - tetralin −5,6,7,
The crude dehydration of 8-d ₄ was obtained as a mixture of isomers.

The crude product of the dehydrated product obtained above was dissolved in n-hexane (26 mL), and 10% Pd-C (70 m
g) was added and the mixture was vigorously stirred at room temperature under a hydrogen atmosphere for 2 hours. After filtration through celite (ethyl acetate), the mother liquor was concentrated under reduced pressure, and the obtained crude product was subjected to silica gel chromatography.
was purified by (n- hexane), 1-phenyl -d _5-4-
(2-phenyl -d ₅ - ethyl) tetralin -5,6,
7,8-d ₄ 2.67g (39 as a colorless oil
%).

[0239] 1-phenyl -d ₅ -4- (2- phenyl -d ₅ - ethyl) tetralin -5,6,7,8-d ₄ a further high performance liquid chromatography (TSKgel OD
S-80TSQA, 80% acetonitrile, 20% water)
At a colorless oil 1S ^* - phenyl -d ₅ -4S ^* - (2-
Phenyl -d ₅ - ethyl) tetralin -5,6,7,8
-D ₄ and, as a colorless oil 1S ^* - phenyl -d ₅ -4R ^* -
(2-phenyl -d ₅ - ethyl) tetralin -5,6,
It was separated into 7,8-d _4.

1S ^* -phenyl-d ₅ -4R ^* -(2-f
Eniru -d ₅ - ethyl) tetralin-5,6,7,8
^{_{d 4 1 H-NMR (CDCL}} 3, TMS) δ: 1.86-2.14 (m, 6H), 2.65-2.
73 (m, 1H), 2.78-2.84 (m, 1H),
2.87-2.92 (m, 1H), 4.07 (dd, 1
H, J = 6.0, 8.4 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 25.2, 29.6, 33.5, 37.3, 38.
9, 45.7, 138.7, 141.2, 141.9,
146.8. Mass EI method: 326 (M ⁺ ).

1S ^* -phenyl-d ₅ -4S ^* -(2-f
Eniru -d ₅ - ethyl) tetralin-5,6,7,8
^{_{d 4 1 H-NMR (CDCL}} 3, TMS) δ: 1.65-1.71 (m, 1H), 1.79-1.
85 (m, 1H), 1.91-2.16 (m, 3H),
2.23-2.28 (m, 1H), 2.63-2.71
(M, 1H), 2.75-2.83 (m, 1H), 2.
93-2.97 (m, 1H), 4.14 (dd, 1H,
J = 6.0, 6.4 Hz). ¹³ C-NMR (CDCL ₃ ) δ: 24.6, 29.9, 33.4, 37.2, 38.
7, 45.3, 139.1, 141.2, 142.2
147.3. Mass EI method: 326 (M ⁺ ).

Production Example 24 1S ^* -phenyl-d ₅ -4S
^* -(2-phenylethyl) tetralin-5,6,7,
8-d ₄ (1S ^* - phenyl -4S ^* - (2- phenylethyl) tetralin -d _9), 1S ^* - phenyl -d ₅ -4
R ^* -(2-phenylethyl) tetralin-5,6,
Method for producing 7,8-d ₄ (1S ^* -phenyl-4R ^* -(2-phenylethyl) tetralin-d ₉ )

The following compounds were produced in the same manner as in Production Example 23, using phenethylmagnesium bromide as the Grignard reagent.

1S ^* -phenyl-d ₅ -4R ^* -(2-f
Eniruechiru) tetralin ^{_{-5,6,7,8-d 4 1 H-NMR}} (CDCL 3, TMS) δ: 1.81-2.18 (m, 6H), 2.63-2.
73 (m, 1H), 2.75-2.85 (m, 1H),
2.85-2.93 (m, 1H), 4.08 (dd, 1
H, J = 7.0, 8.3 Hz), 7.15-7.26
(M, 3H), 7.26-7.31 (m, 1H). ¹³ C-NMR (CDCL ₃ ) δ: 25.3, 29.7, 33.8, 37.5, 39.
1,45.9,125.7,128.3 × 4,139.
0, 141.5, 142.4, 147.1. Mass EI method: 321 (M ⁺ ).

1S ^* -phenyl-d ₅ -4S ^* -(2-f
Eniruechiru) tetralin ^{_{-5,6,7,8-d 4 1 H-NMR}} (CDCL 3, TMS) δ: 1.63-1.72 (m, 1H), 1.79-1.
87 (m, 1H), 1.91-2.17 (m, 3H),
2.22-2.31 (m, 1H), 2.62-2.72
(M, 1H), 2.74-2.83 (m, 1H), 2.
91-2.99 (m, 1H), 4.14 (dd, 1H,
J = 5.8, 6.3 Hz), 7.16-7.32 (m,
5H). ¹³ C-NMR (CDCL ₃ ) δ: 24.7, 30.0, 33.6, 37.3, 38.
8, 45.4, 125.8, 128.4 × 4, 139.
2,141.3,142.6,147.4. Mass EI method: 321 (M ⁺ ).

Next, a specific method for quantifying the styrene trimer will be described with reference to test examples.
It can be understood that the styrene trimer quantification method of the present invention is a highly accurate and significant measurement method.

1) Reagents Ethanol: For analysis of residual phthalates (Katayama Chemical Co., Ltd.); n-hexane: For analysis of residual phthalates (Katayama Chemical Co., Ltd.); Diethyl ether: Analysis of residual phthalates (Katayama Chemical Industry Co., Ltd.); Silica gel: LC-Si (1 g) (Supel
Co.); p-terphenyl: KC special grade (manufactured by Katayama Chemical Industry Co., Ltd.); water: MILLI-Q Labo (MI
Ultrapure water manufactured by LLIPORE

2) Apparatus Gas chromatograph mass spectrometer Gas chromatograph: HP-6890 (HEWLETT)
PACKARD) Mass spectrometer: Auto Mass II (manufactured by JEOL Ltd.) Homogenizer: EXCEL-AUTO HOMOGE
NIZER (Nippon Seiki Seisakusho)

3) GC-MS measurement conditions Column: DB-5 (0.25 mm id × 30)
m, film thickness 0.25 μm), column temperature: 100 ° C. → 20 ° C./min. → 300
° C Injection temperature: 250 ° C Ion source temperature: 250 ° C Inlet temperature: 250 ° C Carrier gas: He (1.3 mL / min.) Ionization voltage: 70 eV Ion acceleration voltage: 3 kV Measurement mode: SIM Scan speed: 50 msec Injection amount: 2 μL (Splitless)

4) Compounds to be measured and surrogate compounds Styrene trimers existing in polystyrene products
2,4,6-triphenyl-1-hexene (ST
1) and 1-phenyl-4- (1-phenylethyl)
Tolarin (ST2) and 1-phenyl-4- (2-
Phenylethyl) tetralin (ST3)
And the surrogate compound is 2,4,6-tri-
Phenyl-d_Fifteen-1-hexene (ST1-d_Fifteen), 1-
Phenyl-d _Five-4- (1-phenylethyl) tetrali
-1,5,6,7,8-d_Five(ST2-d_Ten), 1-
Phenyl-d_Five-4- (2-phenyl-d_Five-Ethyl)
Tralin-5,6,7,8-d_Four(ST3-d₁₄)
Each was used.

The compound to be measured is 10 to 1000 ppb
In addition, the surrogate compound showed linearity in the range of 2 ppb to 50 ppb.

5) Quantitative Experiment In this test, an internal standard method using p-terphenyl as an internal standard was applied. As the monitor ion peak of the compound to be measured, 2,4,6-triphenyl-1-hexene: 91, 1-phenyl-4- (1-phenylethyl)
Tetraline: 129, 1-phenyl-4- (2-phenylethyl) tetralin: 91 was selected, and GC-
The compound to be measured was quantified by MS. (Limit of quantification:
1.0ppb)

The monitor ion peak of the surrogate compound was 2,4,6-triphenyl-d ₁₅ -1.
- hexene: 217,1- phenyl -d ₅ -4- (1-
Phenylethyl) tetralin-1,5,6,7,8-d
_5: 134,1- phenyl -d _{5-4-(2-phenyl} -
d ₅ - ethyl) tetralin -5,6,7,8-d _4: 21
6 were selected, and the addition recovery rate was determined by GC-MS.

Test Example: Instant noodles in meal form
Determination of Tylene trimer (quantification limit: 1.0 ppb)

1) Sample Instant noodles in a PSP (polystyrene paper) container, HIPS (high impact po
lystyrene) Instant noodles in a container

2) Preparation of test solution Pour hot water up to the waterline on foods (noodles, ingredients, soups)
Leave at 0 ° C. for 30 minutes. Transfer the whole amount to a beaker and make a paste with a homogenizer. 10 g of the paste was weighed into a centrifuge tube at the screw mouth, and this was used as a quantitative test solution as a surrogate substance (internal standard substance for analysis of the present invention) ST-1.
50 ng each of d ₁₅ , ST2-d ₁₀ and ST3-d ₁₄
Added. Add 20 mL of ethanol and shake with a shaker.
Shake for a minute. Centrifuge in a centrifuge at 3200 rpm for 10 minutes. Collect all liquid layers and add 10 mL of n-hexane.
Extract three times and concentrate the hexane layer. 1 g of silica gel
Using diethyl ether: n-hexane (5:10
0) Elute with 10 mL. 1.0 μg of an internal standard (p-terphenyl) is added to the eluate, concentrated to about 1.0 mL, and used as a sample. Table 1 shows the results.

Table 1 Apparent transfer amount of styrene trimer and addition recovery rate of surrogate compound in meal form (n = 3, quantification limit 1.0 ppb)

[0258]

[Table 1]

Further, a correction calculation was made from the formula (the transfer amount of the styrene trimer in the instant noodles in the meal form) = (apparent quantification result of the measurement target compound) ÷ (the recovery rate of surrogate compound addition), and The true value of the styrene trimer in instant noodles in a polystyrene container was obtained.
Table 2 shows the results.

Table 2 True values of the transfer amount of styrene trimer in the meal form (n = 3)

[0261]

[Table 2]

From the above results, in a quantitative test of styrene trimer present in a polystyrene product requiring complicated pretreatment such as a meal form, a considerable amount of the styrene trimer to be measured is lost. It is clear that the correction is needed. Therefore, in order to perform appropriate correction, the method of adding the compound of the present invention having almost the same chemical properties as the compound to be measured as an internal standard substance for analysis is extremely useful in the fields of analytical chemistry, food chemistry, and sanitary chemistry. Useful.

[0263]

The compound of the present invention represented by the formula (I), the formula (II) and the formula (III) (the compound represented by the formula (II) has four kinds of stereoisomers and the compound represented by the formula (III) The compound represented by the formula (2) has two types of stereoisomers, which can be separated and purified.) The styrene trimer, which is considered to remain in the polystyrene product, is obtained by taking into account the fission pattern in the mass spectrum. It is a surrogate compound substituted with deuterium.

The parent peak value and fragment peak value in the mass spectrum of these surrogate compounds show larger values by the amount of deuteration. Therefore, not only the parent peak but also each fragment peak can be used as a monitor ion peak in the quantitative analysis of the styrene trimer, which is optimal for the analysis of a styrene trimer having a very small parent peak. Further, since its chemical properties are almost the same as the corresponding styrene trimer, it is a very effective internal standard in a quantitative test of the residual amount of styrene trimer in a polystyrene product requiring complicated pretreatment.

The styrene trimer analysis method using the compound of the present invention is a very high-precision analysis method in which the loss of the styrene trimer, which is inevitable in operation, is corrected. Particularly, since the amount of the styrene trimer eluted from the polystyrene container is extremely small, it has been difficult to measure the amount of the styrene trimer eluted into the food or the like in the polystyrene container with high accuracy in the past. , High-precision analysis became possible.

Continuation of the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) G01N 33/44 G01N 33/44 // C07B 57/00 320 C07B 57/00 320 C07M 5:00 C07M 5:00 7: 00 7:00 (72) Inventor Toshihiro Yamada 4-1-1 Nishinakajima, Yodogawa-ku, Osaka-shi, Nippon Foods Co., Ltd. F-term (reference) 4H006 AA01 AA02 AB90 AC11 AC25 AC84

Claims (15)

[Claims] 1. A compound of the general formula (I) A compound represented by the formula: [Wherein, R ¹ and R ^{2 each} represent a hydrogen atom or a deuterium atom; C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ] 2. A compound of the general formula (II-1) A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ] 3. A compound of the general formula (II-2) A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ] 4. A compound of the general formula (II-3) A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ] 5. A compound of the general formula (II-4) A compound represented by the formula: [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ] 6. A compound of the general formula (III-1) A compound represented by the formula: [Wherein, R ³ represents a phenyl group or a phenyl group in which all hydrogen atoms on a benzene ring are substituted with deuterium atoms; C ₆ D ₅ is a hydrogen atom in which all hydrogen atoms on a benzene ring are substituted with deuterium atoms. Represents a phenyl group. ] 7. A compound of the general formula (III-2) A compound represented by the formula: [Wherein, R ³ represents a phenyl group or a phenyl group in which all hydrogen atoms on a benzene ring have been replaced with deuterium atoms; C ₆ D ₅ has all hydrogen atoms on a benzene ring replaced with deuterium atoms. Represents a phenyl group. ] 8. A process for producing a compound represented by the general formula (I), characterized by a carbon-addition reaction to the compound represented by the general formula (IV). Embedded image [Wherein, R ¹ and R ^{2 each} represent a hydrogen atom or a deuterium atom; C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ] 9. A method for producing a compound represented by the general formula (II), comprising reducing the compound represented by the general formula (V). Embedded image [In the formula, C ₆ D ₅ represents a phenyl group in which all hydrogen atoms on a benzene ring have been substituted with deuterium atoms. ] 10. A method for producing a compound represented by the general formula (III), comprising reducing the compound represented by the general formula (VI). Embedded image [Wherein, R ³ represents a phenyl group or a phenyl group in which all hydrogen atoms on a benzene ring are substituted with deuterium atoms; C ₆ D ₅ is a hydrogen atom in which all hydrogen atoms on a benzene ring are substituted with deuterium atoms. Represents a phenyl group. ] 11. The method according to claim 2, wherein the stereoisomers of the compound of the formula (II) obtained in claim 9 are separated.
5. The method for producing the compound according to any one of the above items 5. 12. The method according to claim 6, wherein the stereoisomers of the compound of the formula (III) obtained in claim 10 are separated. 13. An internal standard substance for analysis comprising the compound according to any one of claims 1 to 7. 14. A quantitative test solution of styrene trimer,
A method for quantifying a styrene trimer, comprising a step of adding the internal standard substance for analysis according to claim 13. 15. A method for quantifying the amount of styrene trimer eluted into a food filled in a polystyrene container, wherein the styrene trimer quantitative test solution is prepared by pouring hot water or water into a polystyrene container filled with a food. The method for quantifying a styrene trimer according to claim 14, which is a solution containing an edible liquid food or a edible food prepared by pouring hot water or water into the edible food.