JP2008169127A - Method for producing naphthopyran compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a naphthopyran compound such as 6,8-dimethoxy-10-methyl-3-(4-dimethylaminophenyl)-3-(4-methoxyphenyl)-2H-naphtho[1,2-b]pyran useful as a photochromic compound in a high yield. <P>SOLUTION: The naphthopyran compound is produced e.g. by reacting a naphthol derivative such as 5,7-dimethoxy-3-methyl-1-naphthol with an aldehyde derivative such as 3-(4-dimethylaminophenyl)-3-(4-methoxyphenyl)propenal in the presence of an arylboronic acid anhydride such as phenylboronic acid anhydride. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a suitable method for producing a naphthopyran compound particularly useful as a photochromic compound.

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

  Among benzopyran compounds, naphthopyran compounds 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 compounds, a method is known in which a naphthol derivative and a propargyl alcohol derivative are stirred and mixed in the presence of an acid catalyst (Patent Document 1). As the acid catalyst, p-toluenesulfonic acid is most commonly used. However, since the catalyst has a strong acidity and a tar component is by-produced, the yield is not necessarily good. In addition, since the naphthopyran compound is not necessarily highly stable against acids, the yield decreases further when the amount of catalyst increases or the reaction time increases, making it difficult to separate from the various by-products produced. There is also a problem of coming. In addition, naphthopyran compounds recently developed as photochromic compounds have complicated structures, and it is not uncommon to require more than 10 steps to obtain a naphthol derivative as a raw material. Therefore, the low yield of the reaction step and the unstable yield are serious problems from the viewpoint of production cost.

  On the other hand, as another method for producing a naphthopyran compound, a method of stirring and mixing a naphthol derivative and an aldehyde derivative in the presence of titanium alkoxide or aryl boronic acid has been reported (see Non-Patent Document 1 and Non-Patent Document 2). . However, these methods have problems such as that the reaction takes a long time and the yield is not so high. In particular, when titanium alkoxide is used, the target product after reaction and titanium There are also problems in the purification process, such as difficulty in separation of the above, and it is difficult to say that the method is industrially suitable.

U.S. Pat. No. 4,931,221 Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (18), 2591 (1994) Canadian Journal of Chemistry, 70 (6), 1717 (1992)

  Accordingly, an object of the present invention is to provide a method capable of producing a naphthopyran compound in a high yield with a short reaction time while suppressing the production of by-products.

  As a result of various studies to solve the above problems, it has been found that a method of reacting a naphthol derivative and an aldehyde derivative in the presence of an arylboronic acid anhydride is extremely effective, and has solved the present problem.

  That is, the present invention provides the following formula (1)

{In the formula, ^one combination of a combination of R ¹ and R ² and a combination of R ³ and R ⁴ is bonded to each other to form the following formula (1A)

(Wherein R ⁵ , R ⁶ , R ⁷ and R ⁸ each independently comprise a hydrogen atom, an alkyl group, an alkoxy group, an aralkoxy group, an amino group, a cyano group, a halogen atom, an aralkyl group, and an aryl group. The carbon atom α is a carbon atom to which R ¹ or R ³ is bonded, and the carbon atom β is a carbon atom to which R ² or R ⁴ is bonded.)
A group that forms a ring represented by
^{R 3} and ^{R 4} in combination with a combination or ^{R 1} and ^{R 2} of ^{R 3} and ^{R 4} are other combinations that do not form a ring represented by the formula (1A), or ^{R 1} and ^{R 2,} Each independently is one selected from the group consisting of a hydrogen atom, an alkyl group, an alkoxy group, an aralkoxy group, an amino group, a cyano group, a halogen atom, an aralkyl group, and an aryl group, or bonded to each other to form the above formula It is a group that forms a ring other than the ring represented by (1A). }
A method for producing a naphthopyran compound represented by
Following formula (2)

^{Wherein, R ^1, R 2, ^{R 3} and ^{R 4} are the same meanings as ^{R 1,} R 2, ^{R 3} and ^{R 4} in Formula (1). }
A naphthol derivative represented by formula (3):

(In the formula, R ⁹ and R ¹⁰ are each independently an alkyl group or an aryl group.)
In the presence of an arylboronic acid anhydride.

  In the method of the present invention in which the naphthol derivative represented by the formula (2) and the aldehyde derivative represented by the formula (3) are reacted in the presence of an arylboronic acid anhydride, the tar component is hardly produced as a by-product. The naphthopyran compound can be obtained. Compared with the conventional method in which the method of the present invention is reacted in the presence of arylboronic acid, the desired product can be obtained in a high yield in a short reaction time. The reason for this is not necessarily clear, but when the reaction was carried out using arylboronic acid anhydride, it was released into the reaction system during the reaction compared to the case where the reaction was carried out using arylboronic acid. Since the amount of water produced is overwhelmingly small, it is presumed that the reaction in which one molecule of water is dehydrated from the naphthol derivative and the aldehyde derivative to produce a naphthopyran compound proceeds more smoothly.

  Furthermore, in the method of the present invention, an alkyl group, an alkoxy group, an aralkoxy group, a method in which a naphthol derivative and propargyl alcohol are reacted in the presence of an acid catalyst such as p-toluenesulfonic acid to obtain a naphthopyran compound, When a naphthol derivative having an electron donating substituent such as an amino group, an aralkyl group, and an aryl group is used, there is an advantage that a particularly high yield can be obtained.

[Object of production method of the present invention]
In the production method of the present invention, a naphthopyran compound represented by the following formula (1) is produced.

Since the compound represented by the above formula (1) is a naphthopyran compound, in the formula (1), any one of the combination of R ¹ and R ² and the combination of R ³ and R ⁴ is bonded to each other. Thus, it is necessary to be a group that forms a “ring represented by the following formula (1A)” that is condensed to the benzene ring of the formula (1).

R ³ and R ⁴ , or R ¹ and R ² in the other combination that does not form the ring represented by the formula (1A) are each independently a hydrogen atom, an alkyl group, an alkoxy group, an aralkoxy group, an amino group It is a group selected from the group consisting of a group, a cyano group, a halogen atom, an aralkyl group, and an aryl group, or a group that is bonded to each other to form a ring other than the ring represented by the formula (1A).

For example, when the combination that forms the ring represented by the above formula (1A) is a combination of R ¹ and R ² , R ³ and R ⁴ are the above groups, respectively, and are represented by the above formula (1A). When the combination that forms the ring to be formed is a combination of R ³ and R ⁴ , R ¹ and R ² are the groups described above.

  Here, the alkyl group is not particularly limited, but in general, an alkyl group having 1 to 6 carbon atoms is preferable. Examples of suitable alkyl groups include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-hexyl group, cyclohexyl group and the like. .

  As an alkoxy group, a C1-C6 alkoxy group is preferable. Specific examples of suitable alkoxy groups include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group, t-butoxy group, n-hexyloxy group, cyclohexyloxy group. Etc.

  Although it does not specifically limit as an aralkoxy group, A C6-C10 aralkoxy group is preferable. Specific examples of suitable aralkoxy groups include phenoxy groups and naphthoxy groups.

  As the amino group, a substituted amino group having a substituent is preferable. As the substituted amino group, an alkylamino group, a dialkylamino group, an arylamino group, or a diarylamino group in which an alkyl group or an aryl group is substituted by 1 or 2 is preferable. Specific examples of suitable substituted amino groups are methylamino, ethylamino, phenylamino, dimethylamino, diethylamino, diphenylamino, morpholino, piperidino, pyrrolidinyl, piperazino, N-methylpiperazino. Group, indolinyl group and the like.

  Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

  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.

The aryl group may have a substituent. Among the aryl groups, an unsubstituted group is preferably an aryl group having 6 to 10 carbon atoms. Illustrative examples of suitable unsubstituted aryl groups include phenyl and naphthyl groups. As the substituted aryl group, one or more hydrogen atoms of the above substituted aryl group are the same alkyl group, alkoxy group, aralkoxy group, amino group, halogen atom as those described as the substituents R ^{1 to} R ^4. And those substituted with an aralkyl group or an aryl group.

In addition, R ¹ and R ² , or R ³ and R ⁴ are bonded to each other to form a ring condensed to the benzene ring of the formula (1) other than the ring represented by the formula (1A). For example, when the ring formed by combining R ¹ and R ² with each other is a carbon atom to which R ¹ of the benzene ring of formula (1) is bonded, a carbon atom to which R ² is bonded , R ¹ and R ² are bonded to each other, and a substituent may be bonded to the ring. Examples of the substituent include the same alkyl group, alkoxy group, aralkoxy group, amino group, cyano group, halogen atom, aralkyl group, and aryl group as those described as the substituents R ^{1 to} R ⁴ .

  Considering the photochromic properties of the finally obtained compound, the ring is preferably a ring having 9 to 12 atoms constituting the ring. The number of atoms constituting this ring does not include the number of substituents bonded to the ring. Specific examples of such rings are indene ring and dihydronaphthalene ring. The indene ring and dihydronaphthalene ring may each have a substituent as described above.

In the formula (1A), R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently a hydrogen atom, alkyl group, alkoxy group, aralkoxy group, amino group, cyano group, halogen atom, aralkyl group, and aryl. One selected from the group consisting of groups. As these groups, those preferred as the substituents R ^{1 to} R ⁴ are similarly suitably employed. In the formula (1A), carbon atom α means a carbon atom to which R ¹ or R ³ is bonded, and carbon atom β means a carbon atom to which R ² or R ⁴ is bonded.

In addition, R ^{1 to} R ⁸ in the above formulas (1) and (1A) from the viewpoint that a particularly high yield is obtained as compared with a method in which a naphthol derivative and a propargyl alcohol derivative are reacted in the presence of an acid catalyst. Two or more of them are particularly preferably groups selected from the group consisting of alkyl groups, alkoxy groups, aralkoxy groups, amino groups, aralkyl groups, and aryl groups. At this time, two or more groups may be the same or different from each other.

  The naphthopyran compound that is the object of the present invention is known as a compound exhibiting photochromic properties, and can be suitably used, for example, as a raw material for producing plastic photochromic lenses. Such naphthopyran compounds are disclosed in, for example, US Pat. No. 6,096,246.

  In the production method of the present invention, when the naphthopyran compound represented by the formula (1) is produced, the naphthol derivative represented by the formula (2) and the aldehyde derivative represented by the formula (3) are converted into an arylboronic acid anhydride. It is characterized by reacting in the presence of. By carrying out like this, reaction advances, without a by-product of a tar component, and the target naphthopyran compound can be obtained efficiently. In the method of the present invention, the target product can be obtained in a high yield in a short reaction time as compared with a method in which a naphthol derivative and an aldehyde derivative are reacted in the presence of an arylboronic acid. Hereinafter, the reaction reagent and reaction conditions used in the present invention will be described.

[Naphthol derivatives]
The naphthol derivative used as a raw material in the present invention is a compound represented by the following formula (2).

In the above formula ^(2), R ^1, R 2, ^{R 3} and ^{R 4} have the same meaning as ^{R 1,} R 2, ^{R 3} and ^{R 4} in each of the formulas (1).

  Specific examples of the naphthol derivative represented by the formula (1) that can be preferably used in the present invention include 1-naphthol, 3-phenyl-1-naphthol, 4-phenyl-1-naphthol, and 7-methoxy-1-. Naphthol, 7,7-spirocyclooctano-5-hydroxy-7H-benzo [C] fluorene, 7,8-dihydro-3-methoxybenzo [C] phenanthren-5-ol, 2-naphthol, 4-methoxy- Examples include 2-naphthol, 4-morpholino-2-naphthol, and 6-methoxy-2-naphthol. From the viewpoint that a high yield can be obtained as compared with a method in which a naphthol derivative and a propargyl alcohol derivative are reacted in the presence of an acid catalyst, specific examples of a particularly preferred naphthol derivative include 5,7-dimethoxy-3. -Methyl-1-naphthol, 6,7-dimethoxy-1-naphthol, 4,6-dimethoxy-2-naphthol and the like can be mentioned.

[Aldehyde derivatives]
The aldehyde derivative used as the other raw material in the present invention is a compound represented by the following formula (3).

In the above formula (3), R ⁹ and R ¹⁰ are each independently an alkyl group or an aryl group.

  As the alkyl group, a linear, branched, or cyclic alkyl group having 1 to 12 carbon atoms can be used. Examples of suitable alkyl groups include methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclohexyl, adamantyl and the like.

As the aryl group, an unsubstituted aryl group and a substituted aryl group can be used. The unsubstituted group is preferably an aryl group having 6 to 10 carbon atoms. Illustrative examples of suitable unsubstituted aryl groups include phenyl and naphthyl groups. As the substituted aryl group, one or two or more hydrogen atoms of the above substituted aryl group are the same alkyl group, alkoxy group, aralkoxy group, amino group, cyano group as those described as the substituents R ^{1 to} R ^4. , Halogen atoms, and aryl groups.

  In addition, the aldehyde derivative represented by the formula (3) can take the (E) and (Z) isomer structures, but when taking such an isomer structure, either one of them alone may be used. It may be a mixture in which both are mixed at an arbitrary ratio.

  In the present invention, it is preferable to use an aldehyde derivative represented by the following formula (4) because a particularly high photochromic property can be obtained.

In the above formula (4), R ¹¹ and R ¹² are each independently an alkyl group, an alkoxy group, an aralkoxy group, an amino group, a cyano group, a halogen atom, an aralkyl group, or an aryl group. Examples of these groups include the same alkyl groups, alkoxy groups, aralkoxy groups, amino groups, cyano groups, halogen atoms, aralkyl groups, and aryl groups as those described as the substituents R ^{1 to} R ⁴ .

  Specific examples of the aldehyde derivative represented by the formula (4) include 3,3-diphenylpropenal, 3- (4-methoxyphenyl) -3-phenylpropenal, 3,3-bis (4-methoxypheno). L) 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-isopropyloxy) Eniru) propenal, 3- (4-dimethylamino-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.

[Arylboronic acid anhydride]
The present invention is most characterized in that the reaction between the naphthol derivative and the aldehyde derivative is carried out in the presence of an arylboronic acid anhydride. This makes it possible to obtain the effects as described above. Here, the arylboronic acid anhydride means an anhydride of boronic acid in which at least one hydrogen atom is substituted with an aryl group. As the aryl group, the same aryl group as in the substituents R ^{1 to} R ⁴ can be preferably used.

  In the present invention, it is particularly preferable to use an arylboronic acid anhydride represented by the following formula (5) because the raw materials are easily obtained and a high reaction yield is obtained.

In the above formula (5), R ¹³ , R ¹⁴ , and R ¹⁵ are each independently selected from the group consisting of alkyl groups, alkoxy groups, aralkoxy groups, amino groups, cyano groups, halogen atoms, aralkyl groups, and aryl groups. It is one kind selected. Examples of these groups include the same alkyl groups, alkoxy groups, aralkoxy groups, amino groups, cyano groups, halogen atoms, aralkyl groups, and aryl groups as those described as the substituents R ^{1 to} R ⁴ . Moreover, c, d, and e in Formula (5) each independently represent an integer of 0 to 3, and when c, d, and e are integers of 2 to 3, each R ^{13 to} R ¹⁵ is respectively They may be different from each other.

  Specific examples of suitably used aryl boronic acid anhydrides include phenyl boronic acid anhydride, 4-methylphenyl boronic acid anhydride, 4-methoxyphenyl boronic acid anhydride, 4-fluorophenyl boronic acid anhydride, Examples include 4-tert-butylphenylboronic acid anhydride and 3-fluoro-4-methoxyphenylboronic acid anhydride. Among these, it is particularly preferable to use phenylboronic acid anhydride from the viewpoint of economy.

[Reaction conditions]
In the production method of the present invention, to react the naphthol derivative with the aldehyde derivative, both raw materials may be mixed in the presence of arylboronic acid. 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, and a solvent such as toluene, xylene, acetonitrile, dichloromethane, methyl isobutyl ketone can be used.

  In the production method of the present invention, the mixing ratio of the naphthol derivative and the aldehyde derivative is not particularly limited. It is suitable to mix at a ratio of 8 to 2 mol, particularly preferably 0.9 to 1.3 mol.

  Further, the mixing ratio of the naphthol derivative and the reaction solvent is not particularly limited, but considering the kettle yield, it is preferably 3 to 1000 times, particularly preferably 5 to 300 times, based on the mass of the naphthol derivative. Most preferably, it is doubled.

  The amount of the aryl boronic acid anhydride used is preferably 0.01 to 50 times the mole based on the number of moles of the naphthol derivative in order to increase a sufficient yield. It is preferable to use 10 times mole, especially 0.1 to 3 times mole.

  In addition to the naphthol derivative, aldehyde derivative, and arylboronic acid anhydride, 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 slightly improving the reaction rate.

  As a mixing method, a method in which all of a naphthol derivative, an aldehyde derivative, an arylboronic acid anhydride and a reaction solvent are charged in a reaction vessel and then stirred and mixed; an arylboronic acid anhydride is added to a mixed solution of a naphthol derivative, an aldehyde derivative and a reaction solvent. Known methods such as adding naphthol derivatives and aldehyde derivatives (which may be dissolved in the reaction solvent) to the mixed solution of arylboronic acid anhydride and reaction solvent are used without particular limitation. it can.

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

  After completion of the reaction, an aqueous alkaline solution such as an aqueous solution of sodium carbonate is added for liquid separation, and the arylboronic acid anhydride is separated and removed as a boronate, and then the organic layer is recovered and the target product is removed by removing the solvent. It can be isolated. When any of the raw materials remains in the organic layer, the target naphthopyran compound can be obtained with a purity of 99% or more by a method such as column chromatography or recrystallization.

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

Example 1
5,7-dimethoxy-3-methyl-1-naphthol 2.18 g (10 mmol), 3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) propenal 2.81 g (10 mmol), phenylboronic anhydride 100 ml of toluene was added to 1.24 g (4 mmol) of the product and 0.3 g (4 mmol) of propionic acid, and the mixture was heated and stirred at 105 ° C. After 5 hours, the conversion was confirmed to be 99% or more by high performance liquid chromatography (HPLC). After cooling to room temperature, the organic layer was concentrated after washing with 100 ml of a 10% aqueous sodium carbonate solution and then with 100 ml of a sodium chloride aqueous solution to obtain a light ocher solid. This was purified by column chromatography and recrystallized from toluene / IPA to give 7,9-dimethoxy-2- (4-dimethylaminophenyl) -2- (4-methoxyphenyl) -5-5 as white powder. 4.18 g of methylbenzo [h] chromene 6,8-dimethoxy-10-methyl- (3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) -2Hnaphtho [1,2-b] pyran Rate 87%).

Example 2
4-morpholino-2-naphthol 2.29 g (10 mmol), 3- (4-methoxyphenyl) -3-phenylpropenal 2.38 g (10 mmol), phenylboronic anhydride 1.24 g (4 mmol) with 100 ml of toluene In addition, the mixture was stirred and heated at 105 ° C. After 6 hours, it was confirmed by HPLC that the conversion was 99% or more. After cooling to room temperature, the organic layer was concentrated after washing with 100 ml of 10% aqueous sodium carbonate solution and then with 100 ml of aqueous sodium chloride solution to obtain a pale yellow solid. This was purified by column chromatography and recrystallized with toluene / IPA to give 3- (4-methoxyphenyl) -6-morpholino-3-phenyl-3H naphtho [2,1-b] as a pale yellow powder. 3.95 g of pyran (yield 88%) was obtained.

Example 3
7,7-spirocyclooctano-5-hydroxy-7H-benzo [C] fluorene 3.28 g (10 mmol), 3- (4-dimethylaminophenyl) -3-phenylpropenal 2.37 g (10 mmol), phenyl 100 ml of toluene was added to 1.24 g (4 mmol) of boronic anhydride and 0.3 g (4 mmol) of propionic acid, and the mixture was heated and stirred at 105 ° C. After 5 hours, the conversion was confirmed to be 99% or more by HPLC. After cooling to room temperature, it was washed with 100 ml of 10% aqueous sodium carbonate solution and then with 100 ml of aqueous sodium chloride solution, and then the organic layer was concentrated to obtain a yellowish green solid. This was purified by column chromatography and recrystallized from acetonitrile to give 3- (4-dimethylaminophenyl) -3-phenyl 13,13-spirocyclooctano-indeno [2,1- f] 5.22 g (93% yield) of naphtho [1,2-b] pyran was obtained.

Example 4
5,7-dimethoxy-3-methyl-1-naphthol 2.18 (10 mmol), 3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) propenal 2.81 g (10 mmol), phenylboronic anhydride 100 ml of toluene was added to 1.24 g (4 mmol) of the product, and the mixture was heated and stirred at 105 ° C. After 7 hours, it was confirmed by HPLC that the conversion was 99% or more. After cooling to room temperature, the organic layer was concentrated after washing with 100 ml of a 10% aqueous sodium carbonate solution and then with 100 ml of a sodium chloride aqueous solution to obtain a light ocher solid. This was purified by column chromatography and recrystallized with toluene / IPA to give 6,8-dimethoxy-10-methyl- (3- (4-dimethylaminophenyl) -3- (4-methoxy) as a white powder. 4.18 g (yield 87%) of phenyl) -2H naphtho [1,2-b] pyran was obtained.

Comparative Example 1
5,7-dimethoxy-3-methyl-1-naphthol 2.18 (10 mmol), 3- (4-dimethylaminophenyl) -3- (4-methoxyphenyl) propenal 2.81 g (10 mmol), phenylboronic acid 1 100 ml of toluene was added to .21 g (10 mmol) and 0.3 g (4 mmol) of propionic acid, and the mixture was heated and stirred at 105 ° C. After 24 hours, it was confirmed by HPLC that the conversion was 99% or more. In addition, when 5 hours passed after the reaction start, when the reaction liquid was sampled and analyzed, the conversion rate at that time was 88%. After completion of the reaction, the mixture was cooled to room temperature and washed with 100 ml of 10% aqueous sodium carbonate solution and then with 100 ml of aqueous sodium chloride solution, and then the organic layer was concentrated to obtain a light ocher solid. This was purified by column chromatography and recrystallized with toluene / IPA to give 6,8-dimethoxy-10-methyl- (3- (4-dimethylaminophenyl) -3- (4-methoxy) as a white powder. Phenyl) -2H naphtho [1,2-b] pyran (3.51 g, yield 73%) was obtained.

Comparative Example 2
5,7-dimethoxy-3-methyl-1-naphthol 2.18 (10 mmol), 1- (4-dimethylaminophenyl) -1- (4-methoxyphenyl) -2-propyn-1-ol 2.81 g ( 10 mmol), p-toluenesulfonic acid monohydrate 0.096 g (0.5 mmol) was added 100 ml of toluene, and the mixture was heated and stirred at 105 ° C. After 6 hours, it was confirmed by HPLC that the conversion was 99% or more. After cooling to room temperature, the organic layer was concentrated after washing with 100 ml of 10% aqueous sodium carbonate solution and then with 100 ml of aqueous sodium chloride solution to obtain a dark red solid. This was purified by column chromatography and recrystallized with toluene / IPA to give 6,8-dimethoxy-10-methyl- (3- (4-dimethylaminophenyl) -3- (4-methoxy) as a white powder. Phenyl) -2H naphtho [1,2-b] pyran 1.39 g (29% yield) was obtained.

  From the comparison between Comparative Example 1 and Examples, it can be seen that the reaction time is significantly increased when phenylboronic acid is used instead of phenylboronic anhydride. Further, as shown in Comparative Example 2, in the reaction using p-toluenesulfonic acid, the yield is remarkably lowered depending on the kind of the naphthol compound, whereas this does not occur in the production method of the present invention. The target product can be obtained in a high yield.

Claims (3)

Following formula (1)

{In the formula, ^one combination of a combination of R ¹ and R ² and a combination of R ³ and R ⁴ is bonded to each other to form the following formula (1A)

(Wherein R ⁵ , R ⁶ , R ⁷ and R ⁸ each independently comprise a hydrogen atom, an alkyl group, an alkoxy group, an aralkoxy group, an amino group, a cyano group, a halogen atom, an aralkyl group, and an aryl group. The carbon atom α is a carbon atom to which R ¹ or R ³ is bonded, and the carbon atom β is a carbon atom to which R ² or R ⁴ is bonded.)
A group that forms a ring represented by
^{R 3} and ^{R 4} in combination with a combination or ^{R 1} and ^{R 2} of ^{R 3} and ^{R 4} are other combinations that do not form a ring represented by the formula (1A), or ^{R 1} and ^{R 2,} Each independently is one selected from the group consisting of a hydrogen atom, an alkyl group, an alkoxy group, an aralkoxy group, an amino group, a cyano group, a halogen atom, an aralkyl group, and an aryl group, or bonded to each other to form the above formula It is a group that forms a ring other than the ring represented by (1A). }
A method for producing a naphthopyran compound represented by
Following formula (2)

^{Wherein, R ^1, R 2, ^{R 3} and ^{R 4} are the same meanings as ^{R 1,} R 2, ^{R 3} and ^{R 4} in Formula (1). }
A naphthol derivative represented by formula (3):

(In the formula, R ⁹ and R ¹⁰ are each independently an alkyl group or an aryl group.)
And an aldehyde derivative represented by formula (I) in the presence of an arylboronic acid anhydride. The method according to claim 1, wherein a compound represented by the following formula (4) is used as the aldehyde derivative.

{Wherein R ¹¹ and R ¹² are each independently one selected from the group consisting of an alkyl group, an alkoxy group, an aralkoxy group, an amino group, a cyano group, a halogen atom, an aralkyl group, and an aryl group, a and b are each independently an integer of 0 to 3, and when a and b are an integer of 2 to 3, each R ¹¹ and R ¹² may be different from each other. } The method according to claim 1 or 2, wherein a compound represented by the following formula (5) is used as the aryl boronic acid anhydride.

Wherein R ¹³ , R ¹⁴ and R ¹⁵ are each independently selected from the group consisting of an alkyl group, an alkoxy group, an aralkoxy group, an amino group, a cyano group, a halogen atom, an aralkyl group, and an aryl group. C, d and e are each independently an integer of 0 to 3, and when c, d and e are integers of 2 to 3, each R ¹³ , R ¹⁴ and R ¹⁵ is each May be different from each other.)