JP5656364B2 - Method for producing naphthopyran derivatives - Google Patents

Description

  The present invention relates to a novel naphthopyran derivative production method for producing a naphthopyran derivative by reacting a compound having excellent storage stability with an aldehyde derivative or a propargyl alcohol derivative.

  Some benzopyran derivatives (sometimes called chromene compounds because they have a chromene skeleton) change their chemical structure and color by irradiation with light containing ultraviolet rays such as sunlight, It is known that when the light irradiation is stopped, the original chemical structure is restored and the coloring disappears, and it is a main component of the photochromic lens currently on the market.

  Among the benzopyran derivatives, naphthopyran derivatives having various substituents are known as compounds that are particularly excellent in photochromic properties such as the speed of color development and durability. As a general method for producing these naphthopyran derivatives, a method of stirring and mixing a naphthol derivative and a propargyl alcohol derivative in the presence of an acid catalyst, and a method of stirring and mixing a naphthol derivative and an aldehyde derivative in the presence of an aryl boronic acid derivative are known. (For example, refer to Patent Document 1, Patent Document 2, and Non-Patent Document 1).

  As described above, naphthol derivatives are very important raw material compounds when synthesizing naphthopyran derivatives having excellent photochromic properties. The naphthol derivative used as a raw material for such a useful naphthopyran derivative is obtained by reacting 2,3-dimethylfuran with benzyne and washing with a saturated aqueous ammonium chloride solution (pH 5), for example. -A method for synthesizing naphthol is known (see Non-Patent Document 1).

U.S. Pat. No. 4,931,221 JP 2008-169127 A APPLIED ORGANOMETALLIC CHEMISTRY 2002; 16: 271-276

  However, according to the study by the present inventors, it has been found that the naphthol derivative itself has low storage stability and cannot be stored for a long time. The naphthol derivative is decomposed in the air to produce a by-product, and this by-product is considered to react with a propargyl alcohol derivative or an aldehyde derivative to reduce the yield of the naphthopyran derivative. Therefore, it was found that the naphthol derivative needs to be reacted with a propargyl alcohol derivative or an aldehyde derivative immediately after synthesis to form a naphthopyran derivative.

  If the storage stability of the raw material of this naphthopyran derivative (for example, naphthol derivative) can be increased, a large amount of naphthopyran derivative can be produced, and cost and production conditions can be improved.

  Accordingly, an object of the present invention is to provide a compound that has high storage stability and can be used as a raw material for a naphthopyran derivative, and to provide a method for producing a naphthopyran derivative using the raw material compound.

  In order to solve the above-mentioned problems, the present inventors have conducted intensive research. And, as a result of paying attention to and studying intermediates generated during the reaction of naphthol derivatives, the compound represented by the following general formula (1) is excellent in storage stability, and is a propargyl alcohol derivative or aldehyde under the same conditions as before. It was found that a high-purity naphthopyran derivative can be produced by reacting with a derivative, and the present invention has been completed.

That is, the present invention
Phenylboronic anhydride, 4-methylphenylboronic anhydride, 4-methoxyphenylboronic anhydride, 4-fluorophenylboronic anhydride, 4-tert-butylphenylboronic anhydride, 3-fluoro-4- Methoxyphenylboronic anhydride, phenylboronic acid, 4-methylphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorophenylboronic acid, 4-tert-butylphenylboronic acid, 3-fluoro-4-methoxyphenylboron In the presence of at least one arylboronic acid derivative selected from acids , the following general formula (1)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group, a primary amino group , a secondary amino group, or a tertiary amino group. group, a heterocyclic group bonded through a nitrogen atom having a nitrogen atom as a hetero atom, an aralkyl group, or an aryl group. )
And a compound represented by the following general formula (2)

(Where
R ⁷ and R ⁸ each have a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group, a primary amino group , a secondary amino group, a tertiary amino group , or a nitrogen atom as a hetero atom, A heterocyclic group bonded by an atom, an aralkyl group, or an aryl group,
a and b are each an integer of 1 to 3, and when a and b are an integer of 2 to 3, each R ⁷ and R ⁸ are different from each other even if they are the same group. It may be a group. ) And an aldehyde derivative represented by
The following general formula (3)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ have the same meaning as in the general formula (1),
R ⁷ , R ⁸ , a, and b have the same meaning as in the general formula (2). )

A method for producing a naphthopyran derivative characterized by producing a naphthopyran derivative represented by the formula:

Also, the present invention is an acid catalyst presence, the following general formula (1)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group , a primary amino group , a secondary amino group, or a tertiary amino group. A heterocyclic group, an aralkyl group, or an aryl group having a nitrogen atom as a hetero atom and bonded by the nitrogen atom. And a compound represented by
The following general formula (4)

(Where
R ⁷ and R ⁸ each have a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group, a primary amino group , a secondary amino group, a tertiary amino group , or a nitrogen atom as a hetero atom, A heterocyclic group bonded by an atom, an aralkyl group, or an aryl group,
a and b are each an integer of 1 to 3, and when a and b are an integer of 2 to 3, each R ⁷ and R ⁸ are different from each other even if they are the same group. It may be a group. )
Is reacted with a propargyl alcohol derivative represented by
The following general formula (3)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ have the same meaning as in the general formula (1),
R ⁷ , R ⁸ , a, and b have the same meaning as in the general formula (4). )
A method for producing a naphthopyran derivative characterized by producing a naphthopyran derivative represented by the formula:

A compound represented by the front following general formula (1), by reacting an aldehyde derivative or propargyl alcohol derivative, can be produced naphthopyran derivatives. This reaction is the same as the reaction of a conventional naphthol derivative with an aldehyde derivative or a propargyl alcohol derivative, and there is no need to change the production conditions.

  Further, this compound itself has high storage stability, and even when the compound after long-term storage is used, the yield of the obtained naphthopyran derivative is not reduced. Therefore, the compound can be suitably used, for example, when a naphthopyran derivative is produced in large quantities, and the production conditions of the naphthopyran derivative can be improved by using the compound as a raw material.

The present invention is a method for producing a naphthopyran derivative using a compound represented by the general formula (1) (hereinafter sometimes referred to as a raw material compound) as a raw material. That is, it is a method for producing a naphthopyran derivative by reacting a raw material compound with an aldehyde derivative or a propargyl alcohol derivative in the presence of an acid catalyst.
First, this raw material compound will be described.

(Raw compound)
In the present invention, the compound used as a raw material for the naphthopyran derivative is represented by the following general formula (1):

It is a compound shown by these.

(Groups R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ )
In the general formula (1), R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group , a primary amino group , A secondary amino group, a tertiary amino group , a heterocyclic group having a nitrogen atom as a heteroatom and bonded by the nitrogen atom, an aralkyl group, or an aryl group.

  Of these groups, the alkyl group is generally an alkyl group having 1 to 6 carbon atoms, such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, or a sec-butyl group. , T-butyl group, n-hexyl group, cyclohexyl group and the like are preferable, and methyl group and isopropyl group are particularly preferable in consideration of the photochromic characteristics of the finally obtained naphthopyran derivative.

  As the alkoxy group, generally an alkoxy group having 1 to 6 carbon atoms such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, a sec-butoxy group, a t-butoxy group, An n-hexyloxy group, a cyclohexyloxy group, and the like are preferable, and a methoxy group is preferable in consideration of the photochromic characteristics of the naphthopyran derivative finally obtained.

Phenoxy group, naphthoxy group may have a substituent, upper Symbol phenoxy group, one or more hydrogen atoms is an alkyl group naphthoxy group, an alkoxy group, aralkoxy group, an amino group, a halogen atom, aralkyl And those substituted with an aryl group.

  The amino group is not limited to a primary amino group, and may be a secondary amino group or a tertiary amino group having a substituent. The substituent of such an amino group is not particularly limited, but an alkyl group or an aryl group is typical. Preferable examples of such a substituted amino group (secondary amino group or tertiary amino group) include alkylamino groups such as methylamino group and ethylamino group; dialkylamino groups such as dimethylamino group and diethylamino group; phenyl An arylamino group such as an amino group; a diarylamino group such as a diphenylamino group; In particular, considering the photochromic properties of the finally obtained naphthopyran derivative, a dimethylamino group is preferred.

  Examples of the heterocyclic group having a nitrogen atom as a hetero atom and bonded with the nitrogen atom include a morpholino group, a piperidino group, a pyrrolidinyl group, a piperazino group, an N-methylpiperazino group, an indolinyl group and the like. Further, the heterocyclic group may have an alkyl group such as a methyl group as a substituent. Examples of the heterocyclic group having such a substituent include 2,6-dimethylmorpholino group, 2,6-dimethylpiperidino group, 2,2,6,6-tetramethylpiperidino group and the like. In particular, considering the photochromic properties of the finally obtained naphthopyran derivative, morpholino groups and piperidino groups are preferred.

  As the aralkyl group, an aralkyl group having 7 to 11 carbon atoms is preferable. Examples of suitable aralkyl groups include benzyl group, phenylethyl group, phenylpropyl group, phenylbutyl group and the like. Further, the aralkyl group may have a substituent, and as the aralkyl group having this substituent, one or more hydrogen atoms of the aralkyl group are an alkyl group, an alkoxy group, an aralkoxy group, an amino group. , Substituted with a halogen atom, an aralkyl group or an aryl group.

The aryl group is preferably an aryl group having 6 to 10 carbon atoms. Examples of suitable aryl groups include phenyl and naphthyl groups. The aryl group may have a substituent, and as the aryl group having the substituent, one or more hydrogen atoms of the aryl group are an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group. And those substituted with a primary amino group , a secondary amino group, a tertiary amino group , a halogen atom, an aralkyl group or an aryl group.

(Suitable raw material compound)
Among the compounds represented by the general formula (1), the compound represented by the following general formula (1A) is preferred for use as a raw material for naphthopyran derivatives and other useful compounds.

(Where
R ^1A and R ^2A are each a hydrogen atom, an alkyl group, a phenoxy group, a naphthoxy group , or an aralkyl group,
R ³ , R ⁴ , R ⁵ and R ⁶ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group , a primary amino group , a secondary amino group, a tertiary amino group , or a nitrogen atom. It is a heterocyclic group, an aralkyl group, or an aryl group that has an atom and is bonded by the nitrogen atom. ).

In the compound represented by the general formula (1A), the groups R ^1A and R ^{2A in} the groups R ¹ and R ² of the general formula (1) are respectively a hydrogen atom, an alkyl group, a phenoxy group, a naphthoxy group , Or it is a compound used as an aralkyl group. Examples of the alkyl group, the aralkoxy group, or the aralkyl group of the groups R ^1A and R ^2A include the same groups as those described for R ^{1 to} R ⁶ in the general formula (1).

In the general formula (1a), the groups R ³ , R ⁴ , R ⁵ , and R ⁶ are the same groups as the general formula (1), and the groups R ³ , R ⁴ , R ⁵ , and R ^{6 are used.} An alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group , a primary amino group , a secondary amino group, a tertiary amino group , a heterocyclic group having a nitrogen atom as a hetero atom, and bonded by the nitrogen atom, an aralkyl group, or Examples of the aryl group include the same groups as those described for R ^{1 to} R ⁶ in the general formula (1).

  Among the compounds represented by the general formula (1A), specific examples of particularly preferable compounds include 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene and 1,4-epoxy-2- Methyl-1,4-dihydronaphthalene, 1,4-epoxy-1,2-diphenyl-1,4-dihydronaphthalene, 1,4-epoxy-2-phenyl-1,4-dihydronaphthalene, 1,4-epoxy -1,2-diphenoxy-1,4-dihydronaphthalene, 1,4-epoxy-2-phenoxy-1,4-dihydronaphthalene, 1,4-epoxy-1,2-dibenzyl-1,4-dihydronaphthalene, 1,4-epoxy-2-benzyl-1,4-dihydronaphthalene, 1,4-epoxy-1,2-dibenzyloxy-1,4-dihydronaphthalene, 1,4-d Xyl-2-benzyloxy-1,4-dihydronaphthalene, 1,4-epoxy-1,2-diisopropyl-1,4-dihydronaphthalene, 1,4-epoxy-2-isopropyl-1,4-dihydronaphthalene, 1,4-epoxy-1,2-dimethyl-6,8-dimethoxy-1,4-dihydronaphthalene, 1,4-epoxy-2-methyl-6,8-dimethoxy-1,4-dihydronaphthalene, 1, 4-epoxy-2methyl-6,8-diphenyl-1,4-dihydronaphthalene, 1,4-epoxy-2methyl-6,8-diphenoxy-1,4-dihydronaphthalene, 1,4-epoxy-2methyl -6,8-dimorpholino-1,4-dihydronaphthalene.

  Further, among the above raw material compounds, the following general formula (1B) is particularly preferable.

(Where
R ^1B is a methyl group or an isopropyl group;
R ^2B is a hydrogen atom or a methyl group,
R ^3B and R ^5B are each a hydrogen atom or a methoxy group. )
It is a compound shown by these. Among the compounds represented by the formula (1B), 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene, 1,4-epoxy-2-isopropyl-1,4-dihydronaphthalene, 1, 4-Epoxy-2-methyl-6,8-dimethoxy-1,4-dihydronaphthalene is most preferable from the viewpoint of obtaining raw materials and the photochromic properties of the finally obtained naphthopyran derivative.

(Method for producing raw material compound)
In the present invention, the raw material compound is not particularly limited, but is preferably produced by the following method.

  The following general formula (5)

(In the formula, R ¹ and R ² have the same meanings as those in the general formula (1).)
A furan derivative represented by the following general formula (6)

(In the formula, R ³ , R ⁴ , R ⁵ , and R ⁶ have the same meanings as in the general formula (1).)
After reacting with the benzyne derivative represented by the above, the raw material compound can be produced by treating the reaction system so as not to be under acidic conditions. As will be described in detail below, treating the reaction system so as not to be in an acidic condition means that no acid is added after the reaction, and the obtained reaction solution is washed with washing water having a pH of 6 or more. That's fine. To confirm that the reaction system is not under acidic conditions, the pH of water obtained by washing the reaction solution with the washing water may be confirmed. If the pH of the water is 6 or more, it can be confirmed that the reaction system is not under acidic conditions.

  The furan derivative is a known compound as described in Non-Patent Document 1, for example. Among them, particularly preferred derivatives are those that can form the preferred raw material compounds. Specifically, 2,3-dimethylfuran, 3-methylfuran, 3-isopropylfuran, 2-phenoxyfuran, 2 -Benzylfuran. Among these, 2,3-dimethylfuran is most preferable from the viewpoint of obtaining raw materials.

  The benzyne derivative is also a known compound as described in Non-Patent Document 1, for example. Since this benzyne derivative is an unstable compound, it is preferably synthesized in a reaction system for reacting with the furan derivative and reacted with the furan derivative immediately after production. The method of synthesizing the benzyne derivative is a method of dropping a benzene derivative having a halogen atom as a substituent on magnesium, for example, 2-bromofluorobenzene, or a method of reacting sodium amide with the benzene derivative, for example, chlorobenzene, Known methods can be used without particular limitation.

  Among them, preferred benzyne derivatives are not particularly limited as long as they can form the preferred raw material compounds. Specifically, benzyne obtained from magnesium and 2-bromofluorobenzene is most preferred from the viewpoint of obtaining raw materials. Is preferred.

  The amount of the benzyne derivative used theoretically may be an equivalent mole per mole of the furan derivative, but when considering the yield, reaction efficiency, etc., 0.5 to It is preferable to use about 10 moles.

  The furan derivative and the benzyne derivative can be reacted by mixing both. The order in which these furan derivatives and benzyne derivatives are mixed is not particularly limited, and these components can be simultaneously added to the mixing vessel and mixed, or one of the components can be put in the mixing vessel first. In addition, the other component can be added into the mixing container later and mixed. Among them, in order to efficiently promote the reaction, in the presence of magnesium, a benzene derivative having a halogen atom as a substituent, for example, 2-bromofluorobenzene is dropped into the furan derivative to drop the benzyne derivative in the reaction system. It is preferable to synthesize it immediately with a furan derivative.

  In addition, the reaction of the furan derivative and the benzyne derivative can be directly reacted with each other, but in consideration of operability, it is preferable to dilute and react with an organic solvent. When an organic solvent is used, the organic solvent to be used can be used without particular limitation as long as it does not inhibit the reaction. Specifically, ethers such as tetrahydrofuran and diethyl ether, aromatic hydrocarbons such as toluene and benzene, and aliphatic hydrocarbons such as hexane, cyclohexane and heptane are used. When the above reaction is carried out in an organic solvent, if the amount of the solvent used is too large, the post-treatment of the reaction becomes complicated, so that it may be used in an amount that does not place an excessive burden on the solvent removal. Specifically, it is preferably 1 to 100 parts by mass, particularly 10 to 20 parts by mass with respect to 1 part by mass of the furan derivative to be used.

  The reaction temperature when mixing the furan derivative and the benzyne derivative is preferably 20 ° C to 120 ° C. The reaction time may be appropriately determined according to other reaction conditions while confirming the degree of reaction progress. Usually, a sufficient yield of the raw material compound can be obtained by the reaction for about 10 minutes to 5 hours. .

(Cleaning conditions)
In the conventional method, after reacting the furan derivative with the benzyne derivative and then washing with a saturated aqueous ammonium chloride solution (pH 5), it is considered that the epoxide moiety is opened and a naphthol derivative is produced. On the other hand, in order to produce the raw material compound of the present invention, after the furan derivative and the benzyne derivative are reacted, washing is performed while maintaining a pH of 6 or more, thereby preventing ring opening of the epoxide moiety. The raw material compound can be produced. Specifically, the reaction solution obtained by reacting the furan derivative with the benzyne derivative is washed with water having a pH of 6 or more, for example, tap water, distilled water, ion-exchanged water, etc. without adding an acid. The raw material compound of the present invention can be produced by washing. When an organic solvent that is easily soluble in water is used for the reaction between the furan derivative and the benzyne derivative, the organic solvent is distilled off as necessary, and an organic solvent that is difficult to dissolve in water is added. What is necessary is just to wash with washing water.

(Identification of raw material compounds)
In this invention, a raw material compound can be obtained by performing the said refinement | purification. About the obtained raw material compound, it can confirm that there is no peak derived from OH group around 5.0 ppm seen in a naphthol derivative by ¹ H-NMR, and a quaternary around 80-90 ppm by ¹³ C-NMR. Carbon can be confirmed, and it can be identified by confirming that there is no OH stretching peak seen in the naphthol derivative at 3000 to 3700 cm ⁻¹ by IR.

(Storage stability and reactivity of raw material compounds)
The raw material compound obtained by the above method will be described in the following examples. However, it does not decompose even when it is left at room temperature as compared with a naphthol derivative. In addition, the naphthopyran derivative can be produced by reacting the raw material compound with an aldehyde derivative or a propargyl alcohol derivative under the same conditions as the naphthol derivative.

  When the raw material compound is reacted with an aldehyde derivative or a propargyl alcohol derivative in the presence of an acid to produce a naphthopyran derivative, the acid is present in the reaction system, so that the ring opens to a naphthol derivative, and the aldehyde derivative, or It is thought to react with propargyl alcohol derivatives. However, this raw material compound is a compound excellent in storage stability without ring opening unless an acid is present. Therefore, the productivity of the naphthopyran derivative can be improved.

  Hereinafter, a method for producing a naphthopyran derivative will be described. First, the reaction between the raw material compound and the aldehyde derivative will be described.

(Reaction of raw material compound with aldehyde derivative: production method of naphthopyran derivative)
In the present invention, a naphthopyran derivative can be produced by reacting the raw material compound with an aldehyde derivative. As the reaction conditions, conditions for reacting a naphthol derivative with an aldehyde derivative can be used as they are. Further, the aldehyde derivative used for the reaction may be appropriately determined in accordance with the desired structure of the naphthopyran derivative. Among these, in order to produce a naphthopyran derivative exhibiting excellent photochromic properties, it is preferable to react with the following aldehyde derivative under the following reaction conditions.

  Specifically, in the presence of an aryl boronic acid derivative, the raw material compound and the following general formula (2)

It is preferable to produce a naphthopyran derivative by reacting with an aldehyde derivative represented by the formula: For the reaction, the aryl boronic acid derivative, the raw material compound, and the aldehyde derivative may be mixed.

(Aldehyde derivative)
In the general formula (2), R ⁷ and R ⁸ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group , a primary amino group , a secondary amino group, a tertiary amino group , or a nitrogen atom. Is a heterocyclic group, an aralkyl group, or an aryl group bonded as a hetero atom and bonded with the nitrogen atom,
a and b are each an integer of 1 to 3, and when a and b are an integer of 2 to 3, each R ⁷ and R ⁸ are different from each other even if they are the same group. It may be a group.

These groups, the same groups as described in group R ¹ to R ⁶ in the starting compound can be exemplified.

  Specific examples of the aldehyde derivative represented by the general formula (2) include 3,3-diphenylpropenal, 3- (4-methoxyphenyl) -3-phenylpropenal, and 3,3-bis (4-methoxy). Phenyl) propenal, 3- (4-dimethylaminophenyl) -3-phenylpropenal, 3- (4-morpholinophenyl) -3-phenylpropenal, 3- (4-piperidinophenyl) -3-phenylpropene Nar, 3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) propenal, 3- (4-methoxyphenyl) -3- (4-morpholinophenyl) propenal, 3- (4-methylphenyl)- 3-phenylpropenal, 3,3-bis (4-methylphenyl) propenal, 3,3-bis (4-isopropylo Shifeniru) propenal, 3- (4-dimethylamino over 3-methylphenyl) -3-phenyl-propenal, and the like. In addition, the thing which can take the (E) and (Z) isomer structure may be either individual, or may be a mixture of arbitrary ratios.

  Among these, considering the photochromic properties of the obtained naphthopyran derivatives, 3,3-diphenylpropenal, 3,3-bis (4-methoxyphenyl) propenal, 3- (4-dimethylaminophenyl) -3-phenylpropene Nar, 3- (4-morpholinophenyl) -3-phenylpropenal, 3- (4-piperidinophenyl) -3-phenylpropenal, 3- (4-dimethylaminophenyl) -3- (4-methoxy Phenyl) propenal, 3- (4-dimethylamino-3-methylphenyl) -3-phenylpropenal is most preferred.

  In the production of the naphthopyran derivative, the amount of the aldehyde derivative used is not particularly limited, but is 0.01 to 50 mol, preferably 0.2 to 10 mol, particularly 1 mol, relative to 1 mol of the raw material compound. Preferably, it is 0.3-3 mol.

(Arylboronic acid derivatives)
The aldehyde derivative and the raw material compound are reacted in the presence of an aryl boronic acid derivative. The aryl boronic acid derivative, full Eniruboron acid anhydride, 4-methylphenyl boronic acid anhydride, 4-methoxyphenylboronic acid anhydride, 4-fluorophenylboronic acid anhydride, 4-tert-butylphenyl boronic acid anhydride 3-fluoro-4-methoxyphenylboronic acid anhydride, phenylboronic acid, 4-methylphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorophenylboronic acid, 4-tert-butylphenylboronic acid, 3 - to use the fluoro-4-methoxyphenyl boronic acid. Among these, it is most preferable to use phenylboronic acid anhydride from the viewpoint of economy.

  In producing the naphthopyran derivative, the amount of the arylboronic acid derivative used is not particularly limited, but is 0.01 to 50 mol, preferably 0.2 to 10 mol, relative to 1 mol of the raw material compound. It is particularly preferable to mix at a ratio of 0.3 to 3 mol.

  In addition to the raw material compound, aldehyde derivative, and arylboronic acid derivative, an acid component such as acetic acid or propionic acid may be added to the reaction system as other additives. The component has a function of improving the reaction rate. Although the usage-amount of this acid component should just be suitably determined according to the quantity and kind of aryl boronic acid derivative to be used, it is preferable that it is 0.1-10 mol with respect to 1 mol of raw material compounds.

(Reaction conditions of raw material compound and aldehyde derivative)
In the present invention, in order to react the raw material compound with the aldehyde derivative, both raw material compounds may be mixed in the presence of the aryl boronic acid derivative. At this time, it is preferable to use a solvent in order to effectively bring the starting compound into contact. The reaction solvent is not particularly limited as long as it is inert to the reaction and dissolves the raw material. Aliphatic hydrocarbons such as cyclohexane, heptane and i-octane, and aromatic hydrocarbons such as toluene and xylene Nitriles such as acetonitrile, halogenated hydrocarbons such as dichloromethane, ketones such as methyl ethyl ketone, and the like can be used.

  The reaction temperature is preferably room temperature to 200 ° C., particularly 70 ° C. to 150 ° C., and the reaction time is preferably 0.01 hours to 48 hours, particularly preferably 0.1 hours to 24 hours. is there.

  As a mixing method, a raw material compound, an aldehyde derivative, an aryl boronic acid derivative, and a reaction solvent are all charged in a reaction vessel and then stirred and mixed. An aryl boronic acid derivative is mixed in a mixed solution of the raw material compound, the aldehyde derivative, and the reaction solvent. Known methods such as a method of adding and stirring and mixing, a method of adding a raw material compound and an aldehyde derivative (which may be dissolved in a reaction solvent) to a mixed solution of an arylboronic acid derivative and a reaction solvent and stirring and mixing are particularly limited. Can be adopted without any problem.

  After completion of the reaction, first, an alkaline aqueous solution such as an aqueous sodium carbonate solution is added and separated to separate and remove the arylboronic acid derivative as a boronate. Subsequently, the target product can be isolated by recovering the organic layer and removing the solvent. Further, when any of the raw materials remains in the organic layer, the target naphthopyran derivative can be obtained with a purity of 99% or more by, for example, purification by a method such as column chromatography or recrystallization.

(Naphthopyran derivatives)
A naphthopyran derivative can be produced by reacting and purifying in the above manner. Among them, when the compound represented by the general formula (2) is used as the aldehyde derivative,
The following general formula (3)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ have the same meaning as in the general formula (1),
R ⁷ , R ⁸ , a, and b have the same meaning as in the general formula (2). )
Can be produced. Such a naphthopyran derivative exhibits excellent photochromic properties.

  Among the naphthopyran derivatives represented by the general formula (3), 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2- b] pyran, 6,8-dimethoxy-10-methyl-3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) -2H naphtho [1,2-b] pyran, 10-isopropyl-3, 3-diphenyl-2H naphtho [1,2-b] pyran and the like are preferable, and among them, 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran is preferable. Most preferred.

  The production of the naphthopyran derivative by the reaction of the raw material compound and the aldehyde derivative has been described above. Next, the production of the naphthopyran derivative by the reaction of the raw material compound and the propargyl alcohol derivative will be described.

(Reaction of raw material compound with propargyl alcohol derivative: production of naphthopyran derivative)
In the present invention, a naphthopyran derivative can be produced by reacting the raw material compound with a propargyl alcohol derivative. As the reaction conditions, the conditions for reacting a naphthol derivative with a propargyl alcohol derivative can be used as they are. Further, the propargyl alcohol derivative used for the reaction may be appropriately determined in accordance with the desired structure of the naphthopyran derivative. Among these, in order to produce a naphthopyran derivative exhibiting excellent photochromic properties, it is preferable to react with the following propargyl alcohol derivative under the following reaction conditions.

  Specifically, in the presence of an acid catalyst, the raw material compound and the following general formula (4)

It is preferable to produce a naphthopyran derivative by reacting with a propargyl alcohol derivative represented by the formula: In order to make it react, an acid catalyst, the said raw material compound, and the said propargyl alcohol derivative should just be mixed.

  By using the propargyl alcohol derivative, it is possible to produce a naphthopyran derivative having the excellent photochromic characteristics described in the reaction between the raw material compound and the aldehyde derivative.

(Propargyl alcohol derivative)
In the general formula (4), R ⁷ and R ⁸ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group , a primary amino group , a secondary amino group, a tertiary amino group , or a nitrogen atom. Is a heterocyclic group, an aralkyl group, or an aryl group bonded as a hetero atom and bonded with the nitrogen atom,
a and b are each an integer of 1 to 3, and when a and b are an integer of 2 to 3, each R ⁷ and R ⁸ are different from each other even if they are the same group. It may be a group.

These groups, the same groups as described in group R ¹ to R ⁶ in the starting compound can be exemplified.

  Specific examples of the propargyl alcohol derivative represented by the general formula (4) include 1,1-diphenyl-2-propyne-1-ol and 1- (4-methoxyphenyl) -1-phenyl-2-propyne. -1-ol, 1,1-bis (4-methoxyphenyl) -2-propyn-1-ol, 1- (4-dimethylaminophenyl) -1-phenyl-2-propyn-1-ol, 1- ( 4-morpholinophenyl) -1-phenyl-2-propyn-1-ol, 1- (4-piperidinophenyl) -1-phenyl-2-propyn-1-ol, 1- (4-dimethylaminophenyl) -1- (4-methoxyphenyl) -2-propyn-1-ol, 1- (4-methoxyphenyl) -1- (4-morpholinophenyl) -2-propyn-1-ol, 1- (4- Tilphenyl) -1-phenyl-2-propyn-1-ol, 1,1-bis (4-methylphenyl) -2-propyn-1-ol, 1,1-bis (4-isopropyloxyphenyl) -2- Propin-1-ol, 1- (4-dimethylamino-3-methylphenyl) -1-phenyl-2-propyn-1-ol and the like can be mentioned. In particular, from the viewpoint of photochromic properties of the obtained naphthopyran derivatives, 1,1-diphenyl-2-propyn-1-ol, 1,1-bis (4-methoxyphenyl) -2-propyn-1-ol, 1- ( 4-dimethylaminophenyl) -1-phenyl-2-propyn-1-ol, 1- (4-morpholinophenyl) -1-phenyl-2-propyn-1-ol, 1- (4-piperidinophenyl) -1-phenyl-2-propyn-1-ol, 1- (4-dimethylaminophenyl) -1- (4-methoxyphenyl) -2-propyn-1-ol, 1- (4-methoxyphenyl) -1 -(4-morpholinophenyl) -2-propyn-1-ol, 1- (4-dimethylamino-3-methylphenyl) -1-phenyl-2-propyn-1-ol are preferred A.

  When the naphthopyran derivative is produced, the amount of the propargyl alcohol derivative used is not particularly limited, but is 0.01 to 50 mol, preferably 0.2 to 10 mol, relative to 1 mol of the raw material compound. Most preferably, it is 0.3-3 mol.

(Acid catalyst)
The acid catalyst used when the raw material compound and the propargyl alcohol derivative are reacted is not particularly limited, and a known acid can be used. Specifically, p-toluenesulfonic acid (including hydrate), methanesulfonic acid, silica gel, alumina, sulfuric acid, camphor sulfonic anhydride and the like. Among these, in consideration of the yield of the obtained naphthopyran derivative, it is preferable to use p-toluenesulfonic acid (including hydrate).

  In the production of the naphthopyran derivative, the amount of the acid catalyst used is not particularly limited, but is 0.01 to 20 mol, preferably 0.02 to 10 mol, particularly preferably relative to 1 mol of the raw material compound. Is preferably mixed at a ratio of 0.05 to 2 mol.

(Reaction conditions for starting compound and propargyl alcohol derivative)
In the present invention, in order to react the raw material compound with the propargyl alcohol derivative, both raw material compounds may be mixed in the presence of an acid catalyst. At this time, it is preferable to use a solvent in order to effectively contact the raw material. The reaction solvent is not particularly limited as long as it is inert to the reaction and dissolves the raw material. Aliphatic hydrocarbons such as cyclohexane, heptane and i-octane, and aromatic hydrocarbons such as toluene and xylene Nitriles such as acetonitrile, halogenated hydrocarbons such as dichloromethane, ketones such as methyl ethyl ketone, and the like can be used.

  The reaction temperature is preferably room temperature to 200 ° C., particularly 70 ° C. to 150 ° C., and the reaction time is preferably 0.01 hours to 48 hours, particularly preferably 0.1 hours to 24 hours. is there.

  As a mixing method, a raw material compound, a propargyl alcohol derivative, an acid catalyst, and a reaction solvent are all charged into a reaction vessel and then stirred and mixed. An acid catalyst is added to a mixture of a raw material compound, a propargyl alcohol derivative, and a reaction solvent. Known methods such as a method of stirring and mixing, a method of adding a raw material compound and a propargyl alcohol derivative (which may be dissolved in a reaction solvent) to a mixed solution of an acid catalyst and a reaction solvent and stirring and mixing can be employed without particular limitation.

  After completion of the reaction, the acid catalyst is first separated and removed by adding and separating an alkaline aqueous solution such as an aqueous sodium carbonate solution. Subsequently, the target product can be isolated by recovering the organic layer and removing the solvent. Further, when any of the raw materials remains in the organic layer, the target naphthopyran derivative can be obtained with a purity of 99% or more by, for example, purification by a method such as column chromatography or recrystallization.

(Naphthopyran derivatives)
A naphthopyran derivative can be produced by reacting and purifying in the above manner. In particular, when the propargyl alcohol derivative represented by the general formula (4) is used, the following general formula (3)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ have the same meaning as in the general formula (1),
R ⁷ , R ⁸ , a, and b have the same meaning as in the general formula (2). )
Can be produced.

  As described above, according to the above conditions, the same naphthopyran derivative as the naphthopyran derivative obtained by the reaction between the raw material compound and the aldehyde derivative can be synthesized.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples.

Example 1
(Synthesis of raw material compound: synthesis of 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene)
Following formula (8)

10 g (0.104 mol) of 2,3-dimethylfuran represented by the following formula and 2.5 g (0.104 mol) of magnesium were dissolved in tetrahydrofuran (THF) (100 ml) and heated to 55 ° C. Next, 17.3 g (0.099 mol) / THF (100 ml) of 2-bromofluorobenzene was added to the reaction solution, and the reaction was performed at 55 ° C. for 2 hours. After completion of the reaction, toluene (100 ml) and water having a pH of 7 (100 ml) were added and washed with water three times. The pH of the water after washing was 9 for the first time, 8 for the second time, 7 for the third time, and it was confirmed that the reaction system was not under acidic conditions. Then, by concentrating the solvent and purifying by column chromatography,
Following formula (9)

1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene 13.8 g (81% yield) was obtained.

(Identification result)
NMR: ¹ H-NMR (500 Hz, CDCl 3, J in Hz) 1.78-1.80 (s × 2, 6H, CH 3), 5.54 (s, 1 H, Ar), 6.48 (s, 1 H) , Ar), 6.96-6.98 (m, 2H, Ar), 7.16-7.17 (m, 2H, Ar).
NMR: ¹³ H-NMR (500 Hz, CDCl 3, J in Hz) 12.7, 13.6, 80.8, 118.4, 119.1, 124.5, 124.9, 136.3, 151.1 , 151.2, 154.4.
IR: 3000-3700 cm ⁻¹ not detected.

Example 2
(Synthesis of naphthopyran derivative: synthesis of 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran)
To a solution of 188 mg (1.09 mmol) / toluene (5.5 ml) of 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene obtained in Example 1,
Following formula (10)

1,1-bis (4-methoxyphenyl) -2-propyn-1-ol 380 mg (1.42 mmol) was added, and the mixture was heated to 95 ° C to 100 ° C. To the reaction solution, 10.6 mg (0.056 mmol) of p-toluenesulfonic acid monohydrate was added and refluxed for 6 hours. After completion of the reaction, washing was performed with a 10% by mass aqueous sodium hydroxide solution (5 ml) and then with water (5 ml) three times. The solvent is concentrated, purified by column chromatography, and recrystallized with toluene / isopropyl alcohol (IPA).
Following formula (11)

160 mg (yield: 34.7%) of 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran represented by

Example 3
(Synthesis of naphthopyran derivative: synthesis of 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran In Example 2, p-toluenesulfone used as an acid catalyst The same procedure as in Example 2 was performed except that the same number of moles of camphor anhydride was used in place of the acid monohydrate, 2,2-bis- (4-methoxyphenyl) -5,6 -86 mg (yield: 18.6%) of dimethylnaphtho- [1,2-b] pyran was obtained.

Example 4
(Synthesis of naphthopyran derivative: synthesis of 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran)
To a solution of 188 mg (1.09 mmol) / toluene (5.5 ml) of 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene obtained in Example 1,
Following formula (12)

3,3-bis (4-methoxyphenyl) propenal 380 mg (1.42 mmol), phenylboronic anhydride 138 mg (0.45 mmol) and propionic acid 40 mg (0.54 mmol) were added, and the mixture was refluxed for 6 hours. . After completion of the reaction, washing was performed with a 5% by mass aqueous sodium carbonate solution (5 ml), followed by washing with water (5 ml) three times. The solvent was concentrated, purified by column chromatography, and recrystallized with toluene / IPA to give 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b 460 mg of pyran (yield: 100%) was obtained.

Example 5
(Synthesis of naphthopyran derivative: synthesis of 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran)
188 mg (1.09 mmol) of 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene obtained in Example 1 was allowed to stand at room temperature (23 ° C.) for 1 week. The same operation as in Example 4 was performed except that 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene was allowed to stand at room temperature for 1 week. The obtained 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran was 435 mg (95% yield).

Example 6
(Synthesis of raw material compound: synthesis of 1,4-epoxy-2-isopropyl-1,4-dihydronaphthalene)
Following formula (13)

10 g (0.091 mol) of 3-isopropylfuran and 2.2 g (0.091 mol) of magnesium were dissolved in THF (100 ml) and heated to 55 ° C. To the reaction solution, 15.1 g (0.086 mol) of 2-bromofluorobenzene / THF (100 ml) was added and reacted at 55 ° C. for 2 hours. After completion of the reaction, toluene (100 ml) and water having a pH of 7 (100 ml) were added and washed with water three times. When the pH of the water after washing was confirmed, it was confirmed that the first time was 9, the second time was 8, the third time was 7, and the reaction system was not under acidic conditions. Then, by concentrating the solvent and purifying by column chromatography,
Following formula (14)

Thus, 12.8 g (yield 80%) of 1,4-epoxy-2-isopropyl-1,4-dihydronaphthalene represented by the following formula was obtained.

(Identification result)
NMR: ¹ H-NMR (500 Hz, CDCl ₃ , J in Hz) 1.11 (s × 2, 6H, CH ₃ ), 2.52 (s, 1H, CH (CH ₃ ) ₂ ), 5.56 ( s, 1H, Ar), 5.64 (s, 1H, Ar), 5.71 (s, 1H, Ar), 6.96-6.98 (m, 2H, Ar), 7.16-7. 17 (m, 2H, Ar).
NMR: ¹³ H-NMR (500 Hz, CDCl ₃ , J in Hz) 20.4, 27.0, 84.3, 85.0, 117.4, 118.1, 125.5, 125.9, 135. 3, 150.1, 150.2, 155.4.
IR: 3000-3700 cm ⁻¹ not detected.

Example 7
(Synthesis of naphthopyran derivative: synthesis of 10-isopropyl-3,3-diphenyl-2H naphtho [1,2-b] pyran)
To the 6.4 g (0.034 mol) / toluene (55 ml) solution of 1,4-epoxy-2-isopropyl-1,4-dihydronaphthalene obtained in Example 6,
Following formula (15)

Then, 7.2 g (0.034 mol) of 1,1-diphenyl-2-propyn-1-ol represented by the formula (1) was added and heated to 95 ° C to 100 ° C. To the reaction solution, 320 mg (1.7 mmol) of p-toluenesulfonic acid was added and refluxed for 6 hours. After completion of the reaction, washing was performed with a 10% by mass aqueous sodium hydroxide solution (100 m) and then with water (100 ml) three times. Concentrate the organic layer, purify it by column chromatography, recrystallize with toluene / IPA,
Following formula (16)

10-isopropyl-3,3-diphenyl-2H naphtho [1,2-b] pyran represented by the formula (1.3) (yield: 10%) was obtained.

Example 8
(Synthesis of naphthopyran derivative: synthesis of 10-isopropyl-3,3-diphenyl-2H naphtho [1,2-b] pyran)
To the 6.4 g (0.034 mol) / toluene (55 ml) solution of 1,4-epoxy-2-isopropyl-1,4-dihydronaphthalene obtained in Example 6,
Following formula (17)

Then, 7.2 g (0.034 mol) of 3,3-diphenylpropenal represented by the formula, 4.3 g (0.014 mol) of phenylboronic acid anhydride and 1.0 g (0.013 mol) of propionic acid were added and refluxed for 6 hours. . After completion of the reaction, washing was performed with a 5% by mass aqueous sodium carbonate solution (100 ml) and then with water (100 ml) three times. The organic layer was concentrated, purified by column chromatography, and recrystallized with toluene / IPA to obtain 5.5 g of 10-isopropyl-3,3-diphenyl-2Hnaphtho [1,2-b] pyran. (Yield: 43%).

Example 9
(Synthesis of raw material compounds: synthesis of 1,4-epoxy-2-methyl-6,8-dimethoxy-1,4-dihydronaphthalene)
Following formula (18)

10 g (0.122 mol) of 3-methylfuran and 3.0 g (0.122 mol) of magnesium represented by were dissolved in THF (100 ml) and heated to 55 ° C. To the reaction solution, 27.1 g (0.116 mol) / THF (100 ml) of 2-bromo-3,5-dimethoxyfluorobenzene was added and reacted at 55 ° C. for 2 hours. After completion of the reaction, toluene (100 ml) and water having a pH of 7 (100 ml) were added and washed with water three times. When the pH of the water after washing was confirmed, it was confirmed that the first time was 9, the second time was 8, the third time was 7, and the reaction system was not under acidic conditions. Then, by concentrating the solvent and purifying by column chromatography,
Following formula (19)

Thus, 20.2 g (yield 80%) of 1,4-epoxy-2-methyl-6,8-dimethoxy-1,2-dihydronaphthalene represented by the following formula was obtained.

(Identification result)
NMR: ¹ H-NMR (500 Hz, CDCl ₃ , J in Hz) 1.71 (s, 3 H, CH ₃ ), 3.72 (s, 3 H, O CH ₃ ), 3.76 (s, 3 H, O _{CH 3), 5.55 (s,} 1H, Ar), 5.63 (s, 1H, Ar), 5.73 (s, 1H, Ar), 6.13 (s, 1H, Ar), 6. 17 (s, 1H, Ar).
NMR: ¹³ H-NMR (500 Hz, CDCl ₃ , J in Hz) 16.0, 56.0, 56.3, 79.5, 85.0, 107.4, 108.1, 116.2, 123. 4, 135.5, 135.9, 155.3, 156.1.
IR: 3000-3700 cm ⁻¹ not detected.

Example 10
(Synthesis of naphthopyran derivative: synthesis of 6,8-dimethoxy-10-methyl-3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) -2H naphtho [1,2-b] pyran)
In a solution of 10.4 g (0.046 mol) / toluene (55 ml) of 1,4-epoxy-2-methyl-6,8-dimethoxy-1,4-dihydronaphthalene obtained in Example 6,
Following formula (20)

1- (4-dimethylaminophenyl) -1- (4-methoxyphenyl) -2-propyn-1-ol 13.0 g (0.046 mol) represented by the above formula was added and heated to 95 ° C to 100 ° C. To the reaction solution, 0.43 g (2.3 mmol) of p-toluenesulfonic acid was added and refluxed for 6 hours. After completion of the reaction, washing was performed with a 10% by mass aqueous sodium hydroxide solution (100 ml) and then with water (100 ml) three times. Concentrate the organic layer, purify it by column chromatography, recrystallize with toluene / IPA,
Following formula (21)

2.22 g of 6,8-dimethoxy-10-methyl-3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) -2Hnaphtho [1,2-b] pyran represented by formula (yield: 10%).

Example 11
(Synthesis of naphthopyran derivative: synthesis of 6,8-dimethoxy-10-methyl-3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) -2H naphtho [1,2-b] pyran)
In a solution of 10.4 g (0.046 mol) / toluene (55 ml) of 1,4-epoxy-2-methyl-6,8-dimethoxy-1,2-dihydronaphthalene obtained in Example 6,
Following formula (22)

3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) propenal represented by 13.0 g (0.046 mol), phenylboronic anhydride 5.7 g (0.018 mol), propionic acid 1.7 g (0.023 mol) was added and refluxed for 6 hours. After completion of the reaction, washing was performed with a 5% by mass aqueous sodium carbonate solution (100 ml) and then with water (100 ml) three times. The organic layer was concentrated, purified by column chromatography, and recrystallized from toluene / IPA to give 6,8-dimethoxy-10-methyl-3- (4-dimethylaminophenyl) -3- (4 -Methoxyphenyl) -2H naphtho [1,2-b] pyran was obtained in 9.5 g (yield: 43%).

Reference example 1
(Synthesis of naphthol derivative: synthesis of 3,4-dimethyl-1-naphthol)
2,3-dimethylfuran 20 g (0.208 mol) and magnesium 5.0 g (0.208 mol) were dissolved in THF (200 ml) and heated to 55 ° C. To the reaction solution, 34.6 g (0.198 mol) of 2-bromofluorobenzene / THF (200 ml) was added and reacted at 55 ° C. for 2 hours. After completion of the reaction, in order to reliably obtain a naphthol derivative, 18% by mass hydrochloric acid was added to the reaction solution and stirred at room temperature for 1 hour. The reaction solution was then washed 3 times with pH 7 water (100 ml). It was confirmed that the pH of the water obtained by the first washing was 1, and the reaction system was under acidic conditions. Furthermore, washing was repeated with water having a pH of 7 until the pH of the water obtained by washing was 6. Then, by concentrating the solvent and purifying by column chromatography,
Following formula (23)

And 28.3 g of 3,4-dimethyl-1-naphthol (yield: 83%).

(Identification result)
NMR: ¹ H-NMR (500 Hz, CDCl ₃ , J in Hz) 2.42 (s, 1 H, CH ₃ ), 2.51 (s, 3 H, CH ₃ ), 5.02 (s, 1 H, OH) 6.67 (s, 1H, Ar), 7.42 (t, J = 7.0, 1H, Ar), 7.51 (t, J = 8.0, 1H, Ar), 7.97 ( d, J = 8.5, 1H, Ar), 8.14 (d, J = 8.0, 1H, Ar).
NMR: ¹³ H-NMR (500 Hz, CDCl ₃ , J in Hz) 14.0, 20.7, 111.8, 121.8, 123.2, 123.6, 123.8, 123.9, 126. 3, 133.1, 133.9, 149.1.
IR: There is a peak at 3000-3700 cm ⁻¹ .

Reference example 2
(Synthesis of naphthopyran derivative: synthesis of 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran)
To the 25-g (0.145 mol) / toluene (625 ml) solution of 3,4-dimethyl-1-naphthol obtained in Comparative Example 1, 42.8 g (0.160 mol) of 3,3-bis (4-methoxyphenyl) propenal. Then, 17.9 g (0.058 mol) of phenylboronic anhydride and 5.4 g (0.073 mol) of propionic acid were added and refluxed for 10 hours. After completion of the reaction, washing was performed with a 5% by mass aqueous sodium carbonate solution (100 ml), followed by washing with water (100 ml) three times. The solvent was concentrated, purified by column chromatography, and recrystallized with toluene / IPA to give 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b Pyran (57.7 g, yield: 94%) was obtained.

Reference example 3
(Synthesis of naphthopyran derivative: synthesis of 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b] pyran)
3,4-Dimethyl-1-naphthol (1 g, 5.8 mmol) synthesized in Reference Example 1 was allowed to stand at room temperature (23 ° C.) for 1 week. To a solution of 3,4-dimethyl-1-naphthol (1 g, 5.8 mmol) / toluene (50 ml) left at room temperature for 1 week, 1.71 g (6.4 mmol) of 3,3-bis (4-methoxyphenyl) propenal was added. ), Phenylboronic anhydride 720 mg (2.3 mmol) and propionic acid 220 mg (2,9 mmol) were added and refluxed for 10 hours. After completion of the reaction, washing was carried out with a 5% by mass aqueous sodium carbonate solution (10 ml), followed by washing with water (10 ml) three times. The solvent was concentrated, purified by column chromatography, and recrystallized with toluene / IPA to give 2,2-bis- (4-methoxyphenyl) -5,6-dimethylnaphtho- [1,2-b Pyran was obtained in a yield of 1.15 g (47% yield).

The results of Example 4, Example 5, Reference Example 2, and Reference Example 3 are summarized in Table 1. By comparing these examples, it is possible to compare the change in the yield of the chromene compound obtained by using the raw material compound left for 1 week at room temperature and the naphthol derivative.
As shown in Table 1, the raw material compound of the present invention shows less decrease in the yield of the obtained naphthopyran derivative even after storage for 1 week at room temperature, compared with the naphthol derivative.

Example 12 (Evaluation of storage stability of raw material compounds)
The storage stability of the raw material compounds obtained in Examples 1, 6, and 9 was evaluated. In industrial production, there is a case of reacting with an aldehyde derivative or a propargyl alcohol derivative without performing purification by column chromatography. Therefore, in the production of the raw material compound, after the reaction was completed, it was washed with water, and then the residual ratio of the raw material compound was evaluated by HPLC (high performance liquid chromatography) when the solvent was concentrated at room temperature (23 ° C.). . As a reference, 3,4-dimethyl-1-naphthol obtained in Reference Example 1 was also evaluated in the same manner. The results are shown in Table 2.

  As is apparent from Table 2, the raw material compound of the present invention was found to be a stable compound with almost no decomposition even when allowed to stand at room temperature for 2 weeks, as compared with the naphthol derivative. In addition, 3,4-dimethyl-1-naphthol, which is a naphthol derivative, showed a significant decrease in residual rate and coloration after standing for 1 week. On the other hand, 1,4-epoxy-1,2-dimethyl-1,4-dihydronaphthalene, 1,4-epoxy-2-isopropyl-1,4-dihydronaphthalene, 1,4-epoxy, which are raw material compounds of the present invention -2-Methyl-6,8-dimethoxy-1,4-dihydronaphthalene was not colored even after being left for 2 weeks.

Claims (2)

Phenylboronic anhydride, 4-methylphenylboronic anhydride, 4-methoxyphenylboronic anhydride, 4-fluorophenylboronic anhydride, 4-tert-butylphenylboronic anhydride, 3-fluoro-4- Methoxyphenylboronic anhydride, phenylboronic acid, 4-methylphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorophenylboronic acid, 4-tert-butylphenylboronic acid, 3-fluoro-4-methoxyphenylboron In the presence of at least one arylboronic acid derivative selected from acids , the following general formula (1)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group, a primary amino group , a secondary amino group, or a tertiary amino group. group, a heterocyclic group bonded through a nitrogen atom having a nitrogen atom as a hetero atom, an aralkyl group, or an aryl group. )
And a compound represented by the following general formula (2)

(Where
R ⁷ and R ⁸ each have a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group, a primary amino group , a secondary amino group, a tertiary amino group , or a nitrogen atom as a hetero atom, A heterocyclic group bonded by an atom, an aralkyl group, or an aryl group,
a and b are each an integer of 1 to 3, and when a and b are an integer of 2 to 3, each R ⁷ and R ⁸ are different from each other even if they are the same group. It may be a group. ) And an aldehyde derivative represented by
The following general formula (3)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ have the same meaning as in the general formula (1),
R ⁷ , R ⁸ , a, and b have the same meaning as in the general formula (2). )

A method for producing a naphthopyran derivative, which comprises producing a naphthopyran derivative represented by the formula: In the presence of an acid catalyst, the following general formula (1)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ are each a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group , a primary amino group , a secondary amino group, or a tertiary amino group. group, a heterocyclic group bonded through a nitrogen atom having a nitrogen atom as a hetero atom, an aralkyl group, or an aryl group. And a compound represented by
The following general formula (4)

(Where
R ⁷ and R ⁸ each have a hydrogen atom, an alkyl group, an alkoxy group, a phenoxy group, a naphthoxy group, a primary amino group , a secondary amino group, a tertiary amino group , or a nitrogen atom as a hetero atom, A heterocyclic group bonded by an atom, an aralkyl group, or an aryl group,
a and b are each an integer of 1 to 3, and when a and b are an integer of 2 to 3, each R ⁷ and R ⁸ are different from each other even if they are the same group. It may be a group. )
Is reacted with a propargyl alcohol derivative represented by
The following general formula (3)

(Where
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ have the same meaning as in the general formula (1),
R ⁷ , R ⁸ , a, and b have the same meaning as in the general formula (4). )
A method for producing a naphthopyran derivative, which comprises producing a naphthopyran derivative represented by the formula: