JP5765229B2 - New deuteration method - Google Patents

Description

  The present invention relates to a novel deuteration method combining dehydrogenation reaction and deuteration reaction.

  Deuterated (deuterated and tritiated) compounds are said to be useful for various purposes. For example, deuterated compounds are very useful for elucidating the reaction mechanism and substance metabolism, and are widely used as labeling compounds. In addition, since the stability and properties of the compound itself are changed by the isotope effect, the compound is also useful as, for example, a pharmaceutical product, an agrochemical product, and an optical fiber. Furthermore, it is also useful as a labeling compound when investigating absorption, distribution, blood concentration, excretion, metabolism, etc. of pharmaceuticals etc. by animal experiments. Therefore, in recent years, research using deuterated (deuterated and tritiated) compounds has been actively conducted in these fields.

  As the deuteration method of the aromatic ring, for example, by reacting with a deuterated solvent in the presence of an activated catalyst selected from a platinum catalyst, a rhodium catalyst, a ruthenium catalyst, a nickel catalyst and a cobalt catalyst, A method for efficiently deuterating an aromatic ring has been reported (Patent Document 1). However, for example, when a condensed ring hydrocarbon such as naphthalene is deuterated by this method, the deuteration rate is low.

  On the other hand, as a method for deuterating a heterocyclic ring, for example, a complex is obtained by reacting with heavy water in the presence of an activated catalyst selected from a palladium catalyst, a platinum catalyst, a rhodium catalyst, a ruthenium catalyst, a nickel catalyst, and a cobalt catalyst. A method for efficiently deuterating a ring has been reported (Patent Document 2). However, even if a compound having a specific structure among the heterocyclic rings (for example, a condensed heterocyclic ring) is deuterated by this method, it cannot be efficiently deuterated.

  Under such circumstances, development of an efficient method for producing a deuteride of a compound having a condensed ring structure having a naphthalene skeleton, a carbazole skeleton, or a heterocyclic skeleton similar thereto is desired.

International Publication No. 2004/011400 International Publication No. 2004/046066

  The present invention has been made in view of the above circumstances, and provides a method for producing an efficient deuteride of a compound having a condensed ring structure having a naphthalene skeleton, a carbazole skeleton, or a heterocyclic skeleton similar thereto. .

In the present invention, in the presence of a catalyst selected from a palladium catalyst, a platinum catalyst, a nickel catalyst, a cobalt catalyst, an iridium catalyst, a rhodium catalyst, and a ruthenium catalyst, the general formula [1]

{In the formula, two R ¹ and four R ² each independently represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group. , X ₁ and X ₄ are each independently a nitrogen atom or the general formula [14]

(Wherein R ³ represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group, an alkoxycarbonyl group, or a general formula [34].

[Wherein R ²⁰ represents the general formula [35].

(In the formula, two R ²¹ and four R ²² each independently represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group. , X ₈ and X ₉ are either represented by the general formula [36]

(Wherein one bond is bonded to T ₁ and the other bond and double bond are bonded to the adjacent carbon atom or nitrogen atom to form a ring), and the other is Represents a nitrogen atom. ), And T ₁ is represented by the general formula [4].

(In the formula, each of four R ¹¹ independently represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group, or an alkoxycarbonyl group). Valent group or general formula [5]

(Wherein (8 + 4m) R ^{12 s} each independently represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group, and m is 0 Or a divalent group represented by 1). ] Is represented. ) Represents a group represented by However, when any _one of X ₁ and X ₄ is a group represented by the general formula [14] and R ³ in the general formula [14] is a group represented by the general formula [34], The other is a nitrogen atom. }, A compound represented by the general formula [2]

{In the formula, 4 R ⁴ and 4 R ⁵ each independently represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group. , X ₂ is an oxygen atom, general formula [15]

(Wherein R ⁶ represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group) or a general formula [16]

[Wherein, two R ^{7 s} independently represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group, an alkoxycarbonyl group, or a general formula [3].

(In the formula, 4 R ⁸ and 4 R ⁹ each independently represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group. , X ₃ represents a nitrogen atom or a general formula [17]

(Wherein R ¹⁰ represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group), and T ₁ represents It represents a bond, a divalent group represented by the general formula [4] or a divalent group represented by the general formula [5]. However, when T ₁ is a bond, X ₃ is a group represented by the general formula [17]. ) Represents a group represented by ] Is represented. }, A compound represented by the general formula [22]

{Wherein, R ¹³ and four R ¹⁴ are each independently, represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group, X ₅ And X ₆ are either nitrogen atoms or the general formula [23]

(Wherein R ¹⁵ represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group).

The other is represented by the general formula [24]

(Wherein R ¹⁶ represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group, an alkoxycarbonyl group, or a general formula [37]

[Wherein R ²³ represents the general formula [38].

(Wherein, R ²⁴ and four R ²⁵ may be each independently represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group, X ₁₀ And X ₁₁ are either the general formula [39]

(Wherein one bond is bonded to T ₁ and the remaining two bonds are bonded to the adjacent carbon atom or nitrogen atom to form a ring), and the other is a nitrogen atom Or general formula [40]

(Wherein R ²⁶ represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group). ), And T ₁ is the same as above. ] Is represented. Or a group represented by the general formula [25]

(In the formula, two R ¹⁷ 's each independently represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group). Represents. } Or a compound represented by the general formula [26]

[Wherein, nine R ^{18 s} independently represent a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group, and X ₇ represents a nitrogen atom. Or the general formula [27]

(Wherein R ¹⁹ represents a hydrogen atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group). Wherein the compound represented by the general formula [6] is reacted with a deuterated solvent.

{Wherein, two R ^1a and four R ^2a are each independently a deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom Represents a hydrogen atom, a hydroxyl group, a carboxyl group or an amino group, and X _1a and X _4a each independently represent a nitrogen atom or a general formula [18]

Wherein R ^3a is an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group, amino group, or general, which may be deuterated. Formula [41]

[Wherein R ^20a represents a general formula [42]

(In the formula, two R ^21a and four R ^22a are each independently a deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom. , A hydrogen atom, a hydroxyl group, a carboxyl group or an amino group, and one of X _8a and X _9a represents a group represented by the general formula [36], and the other represents a nitrogen atom. T _1a is represented by the general formula [9]

(In the formula, each of four R ^{11a s} may be independently deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, Represents a carboxyl group or an amino group.) Or a divalent group represented by the general formula [10]

(In the formula, (8 + 4m) R ^12a are each independently an optionally deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, Represents a hydroxyl group, a carboxyl group or an amino group, and m represents the same as above. ] Is represented. ) Represents a group represented by ) Represents a group represented by However, when either one of X _1a and X _4a is a group represented by the general formula [18] and R ^3a in the general formula [18] is a group represented by the general formula [41], the other Is a nitrogen atom. } Is represented. However, at least one of the hydrogen atoms possessed by the present compound is a deuterium atom. }, A deuteride represented by the general formula [7]

{Wherein, 4 R ^4a and 4 R ^5a are each independently a deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom Represents a hydrogen atom, a hydroxyl group, a carboxyl group or an amino group, and X _2a represents an oxygen atom, a general formula [19]

Wherein R ^6a represents an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group or amino group, which may be deuterated. Or a group represented by the general formula [20]

[In the formula, two R ^7a each independently represents an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, which may be deuterated. , Carboxyl group, amino group or general formula [8]

(In the formula, 4 R ^8a and 4 R ^9a are each independently deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom. Represents a hydrogen atom, a hydroxyl group, a carboxyl group or an amino group, and X _3a represents a nitrogen atom or a general formula [22]

(Wherein R ^10a represents an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group or amino group, which may be deuterated. And T _1a represents a bond, a divalent group represented by the general formula [9] or a divalent group represented by the general formula [10]. However, when T _1a is a bond, X _3a is a group represented by the general formula [22]. ) Represents a group represented by ] Is represented. However, at least one of the hydrogen atoms possessed by the present compound is a deuterium atom. }, A deuteride represented by the general formula [28]

{In the formula, R ^13a and four R ^14a are each independently deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom. Represents a hydroxyl group, a carboxyl group or an amino group, and one of X _5a and X _6a is a nitrogen atom or a general formula [29]

(Wherein R ^15a represents an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group or amino group, which may be deuterated. And the other is a group represented by the general formula [30].

Wherein R ^16a is an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group, amino group, or general, which may be deuterated. Formula [43]

[Wherein R ^23a represents the general formula [44].

(In the formula, each of R ^24a and four R ^25a is independently deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom. , A hydroxyl group, a carboxyl group or an amino group, one of X _10a and X _11a represents a group represented by the above general formula [39], and the other represents a nitrogen atom or a general formula [45].

Wherein R ^26a represents an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group or amino group, which may be deuterated. )). ), And T _1a is the same as above. ] Is represented. Or a group represented by the general formula [31]

(In the formula, two R ^17a are each independently an optionally deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, Represents a carboxyl group or an amino group). However, at least one of the hydrogen atoms possessed by the present compound is a deuterium atom. } Or a general formula [32]

[Wherein, each of nine R ^18a is independently deuterated alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, Represents a carboxyl group or an amino group, and X _7a represents a nitrogen atom or a general formula [33]

(Wherein R ^19a represents an alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group or amino group, which may be deuterated. ) Represents a group represented by However, at least one of the hydrogen atoms possessed by the present compound is a deuterium atom. ] The manufacturing method of the deuteride shown by this.

  When using a conventional method and deuterating a compound having a naphthalene skeleton, carbazole skeleton, indole skeleton or anthracene skeleton directly as a starting material (substrate), for example, the substrate is not deuterated, deuterated Even if it was done, it had the problem that the deuteration rate was low.

  On the other hand, according to the method of the present invention in which the dehydrogenation reaction and the deuteration reaction are carried out in one pot, the above-mentioned problems that the conventional method has had been solved, and a naphthalene skeleton, a carbazole skeleton, an indole skeleton, A deuterated product corresponding to a fused ring structure-containing compound having an anthracene skeleton or a heterocyclic skeleton similar to these can be produced at a high deuteration rate.

  In the present invention, deuterium atom means deuterium (D) atom and / or tritium (T) atom, and deuteration means deuterium and / or tritiated. In the present specification, the deuteration rate means a ratio in which deuterated hydrogen atoms in a compound are replaced with deuterium atoms.

In the general formulas [1] to [5], [14] to [17], [22] to [27], [35], [38] and [40], R ^{1 to} R ¹⁹ , R ²¹ , The alkyl group represented by R ²² , R ²⁴ , R ²⁵ and R ²⁶ may be linear, branched or cyclic, and is preferably linear, and usually has 1 to 20 carbon atoms, preferably Is 1 to 12, more preferably 1 to 10, specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, 1-methylpentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, Neohexyl group, n-heptyl group, isoheptyl group, sec-hep Butyl group, tert-heptyl group, neoheptyl group, n-octyl group, isooctyl group, sec-octyl group, tert-octyl group, neooctyl group, n-nonyl group, isononyl group, sec-nonyl group, tert-nonyl group, Neononyl group, n-decyl group, isodecyl group, sec-decyl group, tert-decyl group, neodecyl group, n-undecyl group, isoundecyl group, sec-undecyl group, tert-undecyl group, neoundecyl group, n-dodecyl group, Isododecyl, sec-dodecyl, tert-dodecyl, n-tridecyl, isotridecyl, sec-tridecyl, tert-tridecyl, neotridecyl, n-tetradecyl, isotetradecyl, sec-tetradecyl, tert -Tetradecyl group, neotetradecyl group, n-pentadecyl group, isopentadecyl group, sec-pentadecyl group, tert-pentadecyl group, neopentadecyl group n-hexadecyl group, isohexadecyl group, sec-hexadecyl group, tert-hexadecyl group, neohexadecyl group, n-heptadecyl group, isoheptadecyl group, sec-heptadecyl group, tert-heptadecyl group, neoheptadecyl group, n-octadecyl group , Isooctadecyl group, sec-octadecyl group, tert-octadecyl group, neooctadecyl group, n-nonadecyl group, isononadecyl group, sec-nonadecyl group, tert-nonadecyl group, neononadecyl group, n-icosyl group, isoicosyl group, sec- Examples include icosyl group, tert-icosyl group, neoicosyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group, cyclodecyl group, cycloundecyl group, and cyclododecyl group. .

The alkoxy group represented by R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R ²⁴ , R ²⁵ and R ²⁶ may be linear, branched or cyclic, and usually has 1 to 12 carbon atoms, preferably Include 1 to 6, more preferably 1 to 3, specifically, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group , Tert-butoxy group, n-pentyloxy group, isopentyloxy group, sec-pentyloxy group, tert-pentyloxy group, neopentyloxy group, n-hexyloxy group, isohexyloxy group, sec-hexyloxy group Tert-hexyloxy group, neohexyloxy group, n-heptyloxy group, isoheptyloxy group, sec-heptyloxy group, tert-heptyloxy group, neoheptyloxy group, n-octyl Ruoxy group, isooctyloxy group, sec-octyloxy group, tert-octyloxy group, neooctyloxy group, n-nonyloxy group, isononyloxy group, sec-nonyloxy group, tert-nonyloxy group, neononyloxy group, n-decyloxy group, isodecyloxy group, sec-decyloxy group, tert-decyloxy group, neodecyloxy group, n-undecyloxy group, isoundecyloxy group, sec-undecyloxy group, tert-undecyloxy group Group, neoundecyloxy group, n-dodecyloxy group, isododecyloxy group, sec-dodecyloxy group, tert-dodecyloxy group, neododecyloxy group, cyclopropoxy group, cyclobutoxy group, cyclopentyloxy group, cyclohexyloxy Group, cycloheptyloxy group, cyclooctyloxy group, cyclononyloxy group, A cyclodecyloxy group, a cycloundecyloxy group, a cyclododecyloxy group, etc. are mentioned.

Examples of the aryl group represented by R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R ²⁴ , R ^25, and R ²⁶ usually include those having 6 to 14 carbon atoms. Specific examples thereof include a phenyl group and a naphthyl group. Group, anthryl group and the like. The aryl group may further have a substituent such as a phenyl group, and specific examples thereof include a biphenyl group.

Examples of the aryloxy group represented by R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R ²⁴ , R ²⁵ and R ²⁶ usually include those having 6 to 14 carbon atoms. Specifically, for example, a phenyloxy group , Naphthyloxy group, anthryloxy group and the like. The aryloxy group may further have a substituent such as a phenyl group, and specific examples thereof include a biphenyloxy group.

Examples of the alkoxycarbonyl group represented by R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R ²⁴ , R ²⁵ and R ²⁶ include those in which a hydroxyl group in a carboxyl group is substituted with an alkoxy group. Specific examples thereof include the same examples as those exemplified for the alkoxy group represented by R ^{1 to} R ¹⁹ .

In the general formulas [6] to [10], [18] to [20], [22], [28] to [33], [42], [43] and [44], R ^{1a to} R ^19a R ^21a , R ^22a , R ^24a , R ^25a and R ^26a may be deuterated alkyl groups such as R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R ²⁴ , R ²⁵ and Examples include those in which at least one hydrogen atom of the alkyl group represented by R ²⁶ is deuterated, and among them, those in which all hydrogen atoms are deuterated are preferable.

Examples of the optionally deuterated alkoxy group represented by R ^{1a to} R ^19a , R ^21a , R ^22a , R ^24a , R ^25a, and R ^26a include R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R ^24. , R ²⁵ and R ²⁶ have at least one hydrogen atom that is deuterated, among which all hydrogen atoms are preferably deuterated.

Examples of the ^optionally deuterated aryl group represented by R ^{1a to} R ^19a , R ^21a , R ^22a , R ^24a , R ^25a, and R ^26a include R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R ^24. , R ²⁵ and R ²⁶ are those in which at least one hydrogen atom of the aryl group is deuterated, among which all hydrogen atoms are deuterated.

Examples of the ^optionally deuterated aryloxy group represented by R ^{1a to} R ^19a , R ^21a , R ^22a , R ^24a , R ^25a and R ^26a include R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R Examples include those in which at least one hydrogen atom of the aryloxy group represented by ²⁴ , R ²⁵ and R ²⁶ is deuterated, and among them, those in which all hydrogen atoms are deuterated are preferable.

As the alkoxycarbonyl group which may be deuterated represented by R ^{1a to} R ^19a , R ^21a , R ^22a , R ^24a , R ^25a and R ^26a , R ^{1 to} R ¹⁹ , R ²¹ , R ²² , R Examples include those in which at least one hydrogen atom of the alkoxycarbonyl group represented by ²⁴ , R ²⁵ and R ²⁶ is deuterated, and among them, those in which all hydrogen atoms are deuterated are preferable.

  m is usually 0 or 1, preferably 0.

  In the divalent group represented by the general formulas [4] and [9], the position of the bond may be in the ortho position, the meta position or the para position, and preferably in the meta position or the para position.

  In the divalent groups represented by the general formulas [5] and [10], the position of the bond is the 4,4′-position of the phenyl groups (or derivatives thereof) at both ends of the divalent group. 3,3′-position or 4,3′-position, preferably 4,4′-position or 3,3′-position.

As a preferable combination of X ₁ and X _{4 in} the general formula [1], for example, (i) X ₁ and X ₄ are both groups represented by the general formula [14], and (ii) X ₁ is nitrogen. An atom, wherein X ₄ is a group represented by the general formula [14], (iii) a group represented by X ₁ is represented by the general formula [14], and X ₄ is a nitrogen atom, (iv) X ₁ is a nitrogen atom, X ₄ is a group represented by the general formula [14] (and R ³ is a group represented by the general formula [34]), (v) X ₁ is a general formula A group represented by [14] (and R ³ is a group represented by the general formula [34]), and X ₄ is a nitrogen atom.

Further, when X ₁ and X ₄ in the general formula [1] are both groups represented by the general formula [14], at least one R ^{3 in the} two general formulas [14] is hydrogen. An atom, a hydroxyl group, a carboxyl group, an amino group, an alkyl group, an alkoxy group, an aryl group, an aryloxy group or an alkoxycarbonyl group.

Of R ^{3 in} the general formula [14], a hydrogen atom or a group represented by the general formula [34] is preferable.

The divalent group represented by the general formula [4] is preferably an unsubstituted group. That is, it is preferable that four R ¹¹ are hydrogen atoms. Similarly, the divalent group represented by the general formula [5] is preferably an unsubstituted group, and specifically, (8 + 4m) R ¹² is a hydrogen atom.

Of X _{2 in} the general formula [2], a group represented by the general formula [15] is preferable.

General formula [16] Among the two R ⁷ in the, those are both hydrogen atoms, it is preferable a group in which one is a hydrogen atom and the other is represented by the general formula [3].

Among X _{3 in} the general formula [3], a nitrogen atom is preferable.

As a preferable combination of X ₅ and X _{6 in} the general formula [22], for example, (i) X ₅ is a group represented by the general formula [23], and X ₆ is a group represented by the general formula [25]. (Ii) X ₅ is a group represented by the general formula [23], X ₆ is a group represented by the general formula [24], (iii) X ₅ is a nitrogen atom, ₆ is a group represented by the general formula [25], (iv) X ₅ is a group represented by the general formula [23], and X ₆ is a group represented by the general formula [24] (and R ¹⁶ Is a group represented by the general formula [37], (v) X ₅ is a nitrogen atom, and X ₆ is a group represented by the general formula [24] (and R ¹⁶ is a general formula [37 And the like.

As a preferable combination of X _1a and X _{4a in} the general formula [6], for example, (i) X _1a and X _4a are both groups represented by the general formula [18], and (ii) X _1a is nitrogen. An atom, wherein X _4a is a group represented by general formula [18], (iii) X _1a is a group represented by general formula [18], and X _4a is a nitrogen atom, (iv) X _1a is a nitrogen atom, X _4a is a group represented by the general formula [18] (and R ^3a is a group represented by the general formula [41]), (v) X _1a is a general formula A group represented by [18] (and R ^3a is a group represented by the general formula [41]), and X _4a is a nitrogen atom.

Further, when X _1a and X _4a in the general formula [6] are both groups represented by the general formula [18], at least one R ^{3a in the} two general formulas [18] is a heavy group. An alkyl group, alkoxy group, aryl group, aryloxy group or alkoxycarbonyl group, deuterium atom, hydrogen atom, hydroxyl group, carboxyl group or amino group which may be hydrogenated.

Among R ^{3a in} the general formula [18], a hydrogen atom or a group represented by the general formula [41] is preferable.

The divalent group represented by the general formula [9] is preferably an unsubstituted group. That is, it is preferable that four R ^11a are hydrogen atoms. Similarly, the divalent group represented by the general formula [10] is preferably unsubstituted, and specifically, (8 + 4m) R ^12a is preferably a hydrogen atom.

Of X _{2a in} the general formula [7], a group represented by the general formula [19] is preferable.

Of the two R ^{7a in} the general formula [20], those in which both are hydrogen atoms, those in which one is a hydrogen atom and the other is a group represented by the general formula [8] are preferable.

Among X _{3a in} the general formula [8], a nitrogen atom is preferable.

As a preferable combination of X _5a and X _{6a in} the general formula [28], for example, (i) X _5a is a group represented by the general formula [29], and X _6a is a group represented by the general formula [31]. (Ii) X _5a is a group represented by the general formula [29], X _6a is a group represented by the general formula [30], (iii) X _5a is a nitrogen atom, _6a is a group represented by the general formula [31], (iv) X _5a is a group represented by the general formula [29], and X _6a is a group represented by the general formula [30] (and R ^16a Is a group represented by the general formula [43], (v) X _5a is a nitrogen atom, X _6a is a group represented by the general formula [30] (and R ^16a is a general formula [43] And the like.

  Preferable specific examples of the compound represented by the general formula [1] include, for example, 1,2,3,4-tetrahydronaphthalene, 5-amino-1,2,3,4-tetrahydronaphthalene, 6-amino-1,2 , 3,4-Tetrahydronaphthalene, 1-methyl-1,2,3,4-tetrahydronaphthalene, 2-methyl-1,2,3,4-tetrahydronaphthalene, 5-methyl-1,2,3,4- Tetrahydronaphthalene, 6-methyl-1,2,3,4-tetrahydronaphthalene, 1-ethyl-1,2,3,4-tetrahydronaphthalene, 2-ethyl-1,2,3,4-tetrahydronaphthalene, 5- Ethyl-1,2,3,4-tetrahydronaphthalene, 6-ethyl-1,2,3,4-tetrahydronaphthalene, 1-isopropyl-1,2,3,4-tetrahydronaphthalene, 2-isopropyl-1,2 , 3,4-tetrahydronaphthalene, 5-isopropyl-1,2,3,4-tetrahydronaphthalene, 6-isopropyl-1,2,3,4-tetrahydronaphthalene, 1-tert-butyl-1,2,3, 4-tetrahydrona Phthalene, 2-tert-butyl-1,2,3,4-tetrahydronaphthalene, 5-tert-butyl-1,2,3,4-tetrahydronaphthalene, 6-tert-butyl-1,2,3,4- Tetrahydronaphthalene, 5-hydroxy-1,2,3,4-tetrahydronaphthalene, 6-hydroxy-1,2,3,4-tetrahydronaphthalene, 5,6,7,8-tetrahydronaphthalene-1-carboxylic acid, 5 , 6,7,8-Tetrahydronaphthalene-2-carboxylic acid, 5,6,7,8-tetrahydroquinoline, 2-methyl-5,6,7,8-tetrahydroquinoline, 3-methyl-5,6,7 , 8-tetrahydroquinoline, 4-methyl-5,6,7,8-tetrahydroquinoline, 5-methyl-5,6,7,8-tetrahydroquinoline, 6-methyl-5,6,7,8-tetrahydroquinoline 7-methyl-5,6,7,8-tetrahydroquinoline, 8-methyl-5,6,7,8-tetrahydroquinoline, 2-ethyl-5,6,7,8-tetrahydroquinoline, 3-ethyl- 5,6,7,8-tetrahydroquinoline, 4-ethyl-5,6,7,8-tetrahydride Quinoline, 5-ethyl-5,6,7,8-tetrahydroquinoline, 6-ethyl-5,6,7,8-tetrahydroquinoline, 7-ethyl-5,6,7,8-tetrahydroquinoline, 8-ethyl -5,6,7,8-tetrahydroquinoline, 2-isopropyl-5,6,7,8-tetrahydroquinoline, 3-isopropyl-5,6,7,8-tetrahydroquinoline, 4-isopropyl-5,6, 7,8-tetrahydroquinoline, 5-isopropyl-5,6,7,8-tetrahydroquinoline, 6-isopropyl-5,6,7,8-tetrahydroquinoline, 7-isopropyl-5,6,7,8-tetrahydro Quinoline, 8-isopropyl-5,6,7,8-tetrahydroquinoline, 2-propyl-5,6,7,8-tetrahydroquinoline, 3-propyl-5,6,7,8-tetrahydroquinoline, 4-propyl -5,6,7,8-tetrahydroquinoline, 5-propyl-5,6,7,8-tetrahydroquinoline, 6-propyl-5,6,7,8-tetrahydroquinoline, 7-propyl-5,6, 7,8-tetrahydroquinoline, 8 -Propyl-5,6,7,8-tetrahydroquinoline, 2-tert-butyl-5,6,7,8-tetrahydroquinoline, 3-tert-butyl-5,6,7,8-tetrahydroquinoline, 4- tert-butyl-5,6,7,8-tetrahydroquinoline, 5-tert-butyl-5,6,7,8-tetrahydroquinoline, 6-tert-butyl-5,6,7,8-tetrahydroquinoline, 7 -tert-butyl-5,6,7,8-tetrahydroquinoline, 8-tert-butyl-5,6,7,8-tetrahydroquinoline, 2-amino-5,6,7,8-tetrahydroquinoline, 3- Amino-5,6,7,8-tetrahydroquinoline, 4-amino-5,6,7,8-tetrahydroquinoline, 2-hydroxy-5,6,7,8-tetrahydroquinoline, 3-hydroxy-5,6 , 7,8-Tetrahydroquinoline, 4-hydroxy-5,6,7,8-tetrahydroquinoline, 5,6,7,8-tetrahydroquinoline-2-carboxylic acid, 5,6,7,8-tetrahydroquinoline- 3-carboxylic acid, 5,6,7,8-tetrahydroquinoline-4-carboxylic acid, 2-methyl-8-hydroxy Ci-5,6,7,8-tetrahydroquinoline, 3-methyl-8-hydroxy-5,6,7,8-tetrahydroquinoline, 4-methyl-8-hydroxy-5,6,7,8-tetrahydroquinoline 8-hydroxy-5,6,7,8-tetrahydroquinoline-2-carboxylic acid, 5,6,7,8-tetrahydroisoquinoline, 1-methyl-5,6,7,8-tetrahydroisoquinoline, 3-methyl -5,6,7,8-tetrahydroisoquinoline, 4-methyl-5,6,7,8-tetrahydroisoquinoline, 5-methyl-5,6,7,8-tetrahydroisoquinoline, 6-methyl-5,6, 7,8-tetrahydroisoquinoline, 7-methyl-5,6,7,8-tetrahydroisoquinoline, 8-methyl-5,6,7,8-tetrahydroisoquinoline, 1-ethyl-5,6,7,8-tetrahydro Isoquinoline, 3-ethyl-5,6,7,8-tetrahydroisoquinoline, 4-ethyl-5,6,7,8-tetrahydroisoquinoline, 5-ethyl-5,6,7,8-tetrahydroisoquinoline, 6-ethyl -5,6,7,8-tetrahydro Norin, 7-ethyl-5,6,7,8-tetrahydroquinoline, 8-ethyl-5,6,7,8-tetrahydroisoquinoline, 2-isopropyl-5,6,7,8-tetrahydroisoquinoline, 3-isopropyl -5,6,7,8-tetrahydroisoquinoline, 4-isopropyl-5,6,7,8-tetrahydroisoquinoline, 5-isopropyl-5,6,7,8-tetrahydroisoquinoline, 6-isopropyl-5,6, 7,8-tetrahydroisoquinoline, 7-isopropyl-5,6,7,8-tetrahydroisoquinoline, 8-isopropyl-5,6,7,8-tetrahydroisoquinoline, 2-propyl-5,6,7,8-tetrahydro Isoquinoline, 3-propyl-5,6,7,8-tetrahydroisoquinoline, 4-propyl-5,6,7,8-tetrahydroisoquinoline, 5-propyl-5,6,7,8-tetrahydroisoquinoline, 6-propyl -5,6,7,8-tetrahydroisoquinoline, 7-propyl-5,6,7,8-tetrahydroisoquinoline, 8-propyl-5,6,7,8-te Lahydroisoquinoline, 1-tert-butyl-5,6,7,8-tetrahydroisoquinoline, 3-tert-butyl-5,6,7,8-tetrahydroisoquinoline, 4-tert-butyl-5,6,7, 8-tetrahydroisoquinoline, 5-tert-butyl-5,6,7,8-tetrahydroisoquinoline, 6-tert-butyl-5,6,7,8-tetrahydroisoquinoline, 7-tert-butyl-5,6,7 , 8-tetrahydroisoquinoline, 8-tert-butyl-5,6,7,8-tetrahydroisoquinoline, 1-amino-5,6,7,8-tetrahydroisoquinoline, 3-amino-5,6,7,8- Tetrahydroisoquinoline, 4-amino-5,6,7,8-tetrahydroisoquinoline, 1-hydroxy-5,6,7,8-tetrahydroisoquinoline, 3-hydroxy-5,6,7,8-tetrahydroisoquinoline, 4- Hydroxy-5,6,7,8-tetrahydroisoquinoline, 5,6,7,8-tetrahydroisoquinoline-1-carboxylic acid, 5,6,7,8-tetrahydroisoquinoline-3-carboxylic acid, 5,6,7 , 8-teto Hydroisoquinoline-4-carboxylic acid, 1,4-bis (5,6,7,8-tetrahydroisoquinolin-1-yl) benzene, 1,3-bis (5,6,7,8-tetrahydroisoquinoline-1- Yl) benzene, 4,4'-bis (5,6,7,8-tetrahydroisoquinolin-1-yl) biphenyl, 3,4'-bis (5,6,7,8-tetrahydroisoquinolin-1-yl) Biphenyl, 3,3'-bis (5,6,7,8-tetrahydroisoquinolin-1-yl) biphenyl, 1,4-bis (4- (5,6,7,8-tetrahydroisoquinolin-1-yl) Phenyl) benzene, 1,4-bis (5,6,7,8-tetrahydroquinolin-2-yl) benzene, 1,3-bis (5,6,7,8-tetrahydroquinolin-2-yl) benzene, 4,4′-bis (5,6,7,8-tetrahydroquinolin-2-yl) biphenyl, 3,4′-bis (5,6,7,8-tetrahydroquinolin-2-yl) biphenyl, 3, 3'-bis (5,6,7,8-tetrahydroquinolin-2-yl) biphenyl, 1, 4-bis (4- (5,6,7,8-tetrahydroquinolin-2-yl) phenyl) benzene and the like, among others, for example, 1,2,3,4-tetrahydronaphthalene, 8-hydroxy-5, 6,7,8-tetrahydroquinoline-2-carboxylic acid, 5,6,7,8-tetrahydroquinoline, 5,6,7,8-tetrahydroisoquinoline and the like are preferable.

  Preferable specific examples of the compound represented by the general formula [2] include, for example, 1,2,3,4-tetrahydrocarbazole, 1-methyl-1,2,3,4-tetrahydrocarbazole, 2-methyl-1,2 , 3,4-Tetrahydrocarbazole, 3-methyl-1,2,3,4-tetrahydrocarbazole, 4-methyl-1,2,3,4-tetrahydrocarbazole, 5-methyl-1,2,3,4- Tetrahydrocarbazole, 6-methyl-1,2,3,4-tetrahydrocarbazole, 7-methyl-1,2,3,4-tetrahydrocarbazole, 8-methyl-1,2,3,4-tetrahydrocarbazole, 1- Ethyl-1,2,3,4-tetrahydrocarbazole, 2-ethyl-1,2,3,4-tetrahydrocarbazole, 3-ethyl-1,2,3,4-tetrahydrocarbazole, 4-ethyl-1,2 , 3,4-Tetrahydrocarbazole, 5-ethyl-1,2,3,4-tetrahydrocarbazole, 6-ethyl-1,2,3,4-tetrahydrocarbazole, 7-ethyl-1,2,3,4- Tetrahydr Carbazole, 8-ethyl-1,2,3,4-tetrahydrocarbazole, 1-isopropyl-1,2,3,4-tetrahydrocarbazole, 2-isopropyl-1,2,3,4-tetrahydrocarbazole, 3-isopropyl -1,2,3,4-tetrahydrocarbazole, 4-isopropyl-1,2,3,4-tetrahydrocarbazole, 5-isopropyl-1,2,3,4-tetrahydrocarbazole, 6-isopropyl-1,2, 3,4-tetrahydrocarbazole, 7-isopropyl-1,2,3,4-tetrahydrocarbazole, 8-isopropyl-1,2,3,4-tetrahydrocarbazole, 1-propyl-1,2,3,4-tetrahydro Carbazole, 2-propyl-1,2,3,4-tetrahydrocarbazole, 3-propyl-1,2,3,4-tetrahydrocarbazole, 4-propyl-1,2,3,4-tetrahydrocarbazole, 5-propyl -1,2,3,4-tetrahydrocarbazole, 6-propyl-1,2,3,4-tetrahydrocarbazole, 7- Lopyl-1,2,3,4-tetrahydrocarbazole, 8-propyl-1,2,3,4-tetrahydrocarbazole, 1-tert-butyl-1,2,3,4-tetrahydrocarbazole, 2-tert-butyl -1,2,3,4-tetrahydrocarbazole, 3-tert-butyl-1,2,3,4-tetrahydrocarbazole, 4-tert-butyl-1,2,3,4-tetrahydrocarbazole, 5-tert- Butyl-1,2,3,4-tetrahydrocarbazole, 6-tert-butyl-1,2,3,4-tetrahydrocarbazole, 7-tert-butyl-1,2,3,4-tetrahydrocarbazole, 8-tert -Butyl-1,2,3,4-tetrahydrocarbazole, 1-amino-1,2,3,4-tetrahydrocarbazole, 2-amino-1,2,3,4-tetrahydrocarbazole, 3-amino-1, 2,3,4-tetrahydrocarbazole, 4-amino-1,2,3,4-tetrahydrocarbazole, 5-amino-1,2,3,4-tetrahydrocarbazole, 6-amino-1,2,3,4 -Tetrahydrocarbazole, 7-amino-1 , 2,3,4-tetrahydrocarbazole, 8-amino-1,2,3,4-tetrahydrocarbazole, 1-hydroxy-1,2,3,4-tetrahydrocarbazole, 2-hydroxy-1,2,3, 4-tetrahydrocarbazole, 3-hydroxy-1,2,3,4-tetrahydrocarbazole, 4-hydroxy-1,2,3,4-tetrahydrocarbazole, 5-hydroxy-1,2,3,4-tetrahydrocarbazole, 6-hydroxy-1,2,3,4-tetrahydrocarbazole, 7-hydroxy-1,2,3,4-tetrahydrocarbazole, 8-hydroxy-1,2,3,4-tetrahydrocarbazole, 1,2,3 , 4-Tetrahydrocarbazole-1-carboxylic acid, 1,2,3,4-tetrahydrocarbazole-2-carboxylic acid, 1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, 1,2,3,4 -Tetrahydrocarbazole-4-carboxylic acid, 1,2,3,4-tetrahydrocarbazole-5-carboxylic acid, 1,2,3,4-tetrahydrocarbazole-6-carb Rubonic acid, 1,2,3,4-tetrahydrocarbazole-7-carboxylic acid, 1,2,3,4-tetrahydrocarbazole-8-carboxylic acid, 1-methoxy-1,2,3,4-tetrahydrocarbazole, 2-methoxy-1,2,3,4-tetrahydrocarbazole, 3-methoxy-1,2,3,4-tetrahydrocarbazole, 4-methoxy-1,2,3,4-tetrahydrocarbazole, 5-methoxy-1 , 2,3,4-tetrahydrocarbazole, 6-methoxy-1,2,3,4-tetrahydrocarbazole, 7-methoxy-1,2,3,4-tetrahydrocarbazole, 8-methoxy-1,2,3, 4-tetrahydrocarbazole, 1-benzyloxy-1,2,3,4-tetrahydrocarbazole, 2-benzyloxy-1,2,3,4-tetrahydrocarbazole, 3-benzyloxy-1,2,3,4- Tetrahydrocarbazole, 4-benzyloxy-1,2,3,4-tetrahydrocarbazole, 5-benzyloxy-1,2,3,4-tetrahydrocarbazole, 6- Benzyloxy-1,2,3,4-tetrahydrocarbazole, 7-benzyloxy-1,2,3,4-tetrahydrocarbazole, 8-benzyloxy-1,2,3,4-tetrahydrocarbazole, 1,4-bis (1,2,3,4-tetrahydrocarbazol-9-yl) benzene, 1,3-bis (1,2,3,4-tetrahydrocarbazol-9-yl) benzene, 3,4'-bis (1, 2,3,4-tetrahydrocarbazol-9-yl) biphenyl, 4,4'-bis (1,2,3,4-tetrahydrocarbazol-9-yl) biphenyl, 1,4-bis (4- (1, 2,3,4, -tetrahydrocarbazol-9-yl) phenyl) benzene, 1- (3- (1,2,3,4, -tetrahydrocarbazol-9-yl) phenyl) -4- (4- (1 , 2,3,4, -tetrahydrocarbazol-9-yl) phenyl) benzene, 1,4-bis (3- (1,2,3,4, -tetrahydrocarbazol-9-yl) phenyl) benzene, 4, 4'-bis (1,2,3,4-tetrahydrocarbazol-9-yl) bi Enyl, 1,2,3,4-tetrahydrofluorene, 1-methyl-1,2,3,4-tetrahydrofluorene, 2-methyl-1,2,3,4-tetrahydrofluorene, 3-methyl-1,2 , 3,4-Tetrahydrofluorene, 4-methyl-1,2,3,4-tetrahydrofluorene, 5-methyl-1,2,3,4-tetrahydrofluorene, 6-methyl-1,2,3,4- Tetrahydrofluorene, 7-methyl-1,2,3,4-tetrahydrofluorene, 8-methyl-1,2,3,4-tetrahydrofluorene, 9,9-dimethyl-1,2,3,4-tetrahydrofluorene, 1-ethyl-1,2,3,4-tetrahydrofluorene, 2-ethyl-1,2,3,4-tetrahydrofluorene, 3-ethyl-1,2,3,4-tetrahydrofluorene, 4-ethyl-1 , 2,3,4-tetrahydrofluorene, 5-ethyl-1,2,3,4-tetrahydrofluorene, 6-ethyl-1,2,3,4-tetrahydrofluorene, 7-ethyl-1,2,3, 4-tetrahydrofluorene, 8-ethyl-1,2,3,4-tetrahydrofur Orene, 9,9-diethyl-1,2,3,4-tetrahydrofluorene, 1-isopropyl-1,2,3,4-tetrahydrofluorene, 2-isopropyl-1,2,3,4-tetrahydrofluorene, 3 -Isopropyl-1,2,3,4-tetrahydrofluorene, 4-isopropyl-1,2,3,4-tetrahydrofluorene, 5-isopropyl-1,2,3,4-tetrahydrofluorene, 6-isopropyl-1, 2,3,4-tetrahydrofluorene, 7-isopropyl-1,2,3,4-tetrahydrofluorene, 8-isopropyl-1,2,3,4-tetrahydrofluorene, 1-propyl-1,2,3,4 -Tetrahydrofluorene, 2-propyl-1,2,3,4-tetrahydrofluorene, 3-propyl-1,2,3,4-tetrahydrofluorene, 4-propyl-1,2,3,4-tetrahydrofluorene, 5 -Propyl-1,2,3,4-tetrahydrofluorene, 6-propyl-1,2,3,4-tetrahydrofluorene, 7-propyl-1,2,3,4-tetrahydrofluorene 8-propyl-1,2,3,4-tetrahydrofluorene, 9,9-dipropyl-1,2,3,4-tetrahydrofluorene, 1-tert-butyl-1,2,3,4-tetrahydrofluorene 2-tert-butyl-1,2,3,4-tetrahydrofluorene, 3-tert-butyl-1,2,3,4-tetrahydrofluorene, 4-tert-butyl-1,2,3,4-tetrahydro Fluorene, 5-tert-butyl-1,2,3,4-tetrahydrofluorene, 6-tert-butyl-1,2,3,4-tetrahydrofluorene, 7-tert-butyl-1,2,3,4- Tetrahydrofluorene, 8-tert-butyl-1,2,3,4-tetrahydrofluorene, 1-amino-1,2,3,4-tetrahydrofluorene, 2-amino-1,2,3,4-tetrahydrofluorene, 3-amino-1,2,3,4-tetrahydrofluorene, 4-amino-1,2,3,4-tetrahydrofluorene, 5-amino-1,2,3,4-tetrahydrofluorene, 6-amino-1 , 2,3,4-Tetrahydrofluorene, 7-amino-1,2,3,4-tetrahydrofluorene Len, 8-amino-1,2,3,4-tetrahydrofluorene, 9-amino-1,2,3,4-tetrahydrofluorene, 1-hydroxy-1,2,3,4-tetrahydrofluorene, 2-hydroxy -1,2,3,4-tetrahydrofluorene, 3-hydroxy-1,2,3,4-tetrahydrofluorene, 4-hydroxy-1,2,3,4-tetrahydrofluorene, 5-hydroxy-1,2, 3,4-tetrahydrofluorene, 6-hydroxy-1,2,3,4-tetrahydrofluorene, 7-hydroxy-1,2,3,4-tetrahydrofluorene, 8-hydroxy-1,2,3,4-tetrahydro Fluorene, 1,2,3,4-tetrahydrofluorene-1-carboxylic acid, 1,2,3,4-tetrahydrofluorene-2-carboxylic acid, 1,2,3,4-tetrahydrofluorene-3-carboxylic acid, 1,2,3,4-tetrahydrofluorene-4-carboxylic acid, 1,2,3,4-tetrahydrofluorene-5-carboxylic acid, 1,2,3,4-tetrahydrofluorene-6-carboxylic acid, 2,3,4- Torahydrofluorene-7-carboxylic acid, 1,2,3,4-tetrahydrofluorene-8-carboxylic acid, 1-methoxy-1,2,3,4-tetrahydrofluorene, 2-methoxy-1,2,3, 4-tetrahydrofluorene, 3-methoxy-1,2,3,4-tetrahydrofluorene, 4-methoxy-1,2,3,4-tetrahydrofluorene, 5-methoxy-1,2,3,4-tetrahydrofluorene, 6-methoxy-1,2,3,4-tetrahydrofluorene, 7-methoxy-1,2,3,4-tetrahydrofluorene, 8-methoxy-1,2,3,4-tetrahydrofluorene, 1-benzyloxy- 1,2,3,4-tetrahydrofluorene, 2-benzyloxy-1,2,3,4-tetrahydrofluorene, 3-benzyloxy-1,2,3,4-tetrahydrofluorene, 4-benzyloxy-1, 2,3,4-tetrahydrofluorene, 5-benzyloxy-1,2,3,4-tetrahydrofluorene, 6-benzyloxy-1,2,3,4-tetrahydrofluorene, 7-benzene Benzyloxy-1,2,3,4-tetrahydrofluorene, 8-benzyloxy-1,2,3,4-tetrahydrofluorene, and the like. Among them, for example, 1,2,3,4-tetrahydrocarbazole is preferable.

  Preferable specific examples of the compound represented by the general formula [22] include, for example, 4,5,6,7-tetrahydroindole, 2-methyl-4,5,6,7-tetrahydroindole, 3-methyl-4,5 , 6,7-tetrahydroindole, 4-methyl-4,5,6,7-tetrahydroindole, 5-methyl-4,5,6,7-tetrahydroindole, 6-methyl-4,5,6,7- Tetrahydroindole, 7-methyl-4,5,6,7-tetrahydroindole, 2-ethyl-4,5,6,7-tetrahydroindole, 3-ethyl-4,5,6,7-tetrahydroindole, 4- Ethyl-4,5,6,7-tetrahydroindole, 5-ethyl-4,5,6,7-tetrahydroindole, 6-ethyl-4,5,6,7-tetrahydroindole, 7-ethyl-4,5 , 6,7-tetrahydroindole, 2-propyl-4,5,6,7-tetrahydroindole, 3-propyl-4,5,6,7-tetrahydroindole, 4-propyl-4,5,6,7- Tetrahydroindole, 5-propyl -4,5,6,7-tetrahydroindole, 6-propyl-4,5,6,7-tetrahydroindole, 7-propyl-4,5,6,7-tetrahydroindole, 2-isopropyl-4,5, 6,7-tetrahydroindole, 3-isopropyl-4,5,6,7-tetrahydroindole, 4-isopropyl-4,5,6,7-tetrahydroindole, 5-isopropyl-4,5,6,7-tetrahydro Indole, 6-isopropyl-4,5,6,7-tetrahydroindole, 7-isopropyl-4,5,6,7-tetrahydroindole, 2-tert-butyl-4,5,6,7-tetrahydroindole, 3 -tert-butyl-4,5,6,7-tetrahydroindole, 4-tert-butyl-4,5,6,7-tetrahydroindole, 5-tert-butyl-4,5,6,7-tetrahydroindole, 6-tert-butyl-4,5,6,7-tetrahydroindole, 7-tert-butyl-4,5,6,7-tetrahydroindole, 2-amino-4,5,6,7-tetrahydroindole, 3 -Amino-4,5,6,7-te Lahydroindole, 2-hydroxy-4,5,6,7-tetrahydroindole, 3-hydroxy-4,5,6,7-tetrahydroindole, 4,5,6,7-tetrahydroindole-2-carboxylic acid, 4,5,6,7-tetrahydroindole-3-carboxylic acid, 4,5,6,7-tetrahydroisoindole, 1-methyl-4,5,6,7-tetrahydroisoindole, 3-methyl-4, 5,6,7-tetrahydroisoindole, 4-methyl-4,5,6,7-tetrahydroisoindole, 5-methyl-4,5,6,7-tetrahydroisoindole, 6-methyl-4,5, 6,7-tetrahydroisoindole, 7-methyl-4,5,6,7-tetrahydroisoindole, 1-ethyl-4,5,6,7-tetrahydroisoindole, 3-ethyl-4,5,6, 7-tetrahydroisoindole, 4-ethyl-4,5,6,7-tetrahydroisoindole, 5-ethyl-4,5,6,7-tetrahydroisoindole, 6-ethyl-4,5,6,7- Tetrahydroisoin 7-ethyl-4,5,6,7-tetrahydroisoindole, 1-propyl-4,5,6,7-tetrahydroisoindole, 3-propyl-4,5,6,7-tetrahydroisoindole 4-propyl-4,5,6,7-tetrahydroisoindole, 5-propyl-4,5,6,7-tetrahydroisoindole, 6-propyl-4,5,6,7-tetrahydroisoindole, 7 -Propyl-4,5,6,7-tetrahydroisoindole, 1-isopropyl-4,5,6,7-tetrahydroisoindole, 3-isopropyl-4,5,6,7-tetrahydroisoindole, 4-isopropyl -4,5,6,7-tetrahydroisoindole, 5-isopropyl-4,5,6,7-tetrahydroisoindole, 6-isopropyl-4,5,6,7-tetrahydroisoindole, 7-isopropyl-4 , 5,6,7-tetrahydroisoindole, 1-tert-butyl-4,5,6,7-tetrahydroisoindole, 3-tert-butyl-4,5,6,7-tetrahydro Soindole, 4-tert-butyl-4,5,6,7-tetrahydroisoindole, 5-tert-butyl-4,5,6,7-tetrahydroisoindole, 6-tert-butyl-4,5,6 , 7-tetrahydroisoindole, 7-tert-butyl-4,5,6,7-tetrahydroisoindole, 1-amino-4,5,6,7-tetrahydroisoindole, 3-amino-4,5,6 , 7-Tetrahydroisoindole, 1-hydroxy-4,5,6,7-tetrahydroisoindole, 3-hydroxy-4,5,6,7-tetrahydroisoindole, 4,5,6,7-tetrahydroisoindole 1-carboxylic acid, 4,5,6,7-tetrahydroisoindole-3-carboxylic acid, 4,5,6,7-tetrahydroindene, 2-methyl-4,5,6,7-tetrahydroindene, 3 -Methyl-4,5,6,7-tetrahydroindene, 4-methyl-4,5,6,7-tetrahydroindene, 5-methyl-4,5,6,7-tetrahydroindene, 6-methyl-4, 5,6,7-tetrahydroindene, 7-me 4,5,6,7-tetrahydroindene, 2-ethyl-4,5,6,7-tetrahydroindene, 3-ethyl-4,5,6,7-tetrahydroindene, 4-ethyl-4,5 , 6,7-Tetrahydroindene, 5-ethyl-4,5,6,7-tetrahydroindene, 6-ethyl-4,5,6,7-tetrahydroindene, 7-ethyl-4,5,6,7- Tetrahydroindene, 2-propyl-4,5,6,7-tetrahydroindene, 3-propyl-4,5,6,7-tetrahydroindene, 4-propyl-4,5,6,7-tetrahydroindene, 5- Propyl-4,5,6,7-tetrahydroindene, 6-propyl-4,5,6,7-tetrahydroindene, 7-propyl-4,5,6,7-tetrahydroindene, 2-isopropyl-4,5 , 6,7-tetrahydroindene, 3-isopropyl-4,5,6,7-tetrahydroindene, 4-isopropyl-4,5,6,7-tetrahydroindene, 5-isopropyl-4,5,6,7- Tetrahydroindene, 6-isopropyl-4,5,6,7-tetrahydroi Densyl, 7-isopropyl-4,5,6,7-tetrahydroindene, 2-tert-butyl-4,5,6,7-tetrahydroindene, 3-tert-butyl-4,5,6,7-tetrahydroindene 4-tert-butyl-4,5,6,7-tetrahydroindene, 5-tert-butyl-4,5,6,7-tetrahydroindene, 6-tert-butyl-4,5,6,7-tetrahydro Indene, 7-tert-butyl-4,5,6,7-tetrahydroindene, 2-amino-4,5,6,7-tetrahydroindene, 3-amino-4,5,6,7-tetrahydroindene, 2 -Hydroxy-4,5,6,7-tetrahydroindene, 3-hydroxy-4,5,6,7-tetrahydroindene, 4,5,6,7-tetrahydroindene-2-carboxylic acid, 4,5,6 , 7-Tetrahydroindene-3-carboxylic acid, 1,4-bis (4,5,6,7-tetrahydro-1H-indazol-1-yl) benzene, 1,3-bis (4,5,6,7 -Tetrahydro-1H-indazol-1-yl) benzene, 4,4'-bis (4,5,6,7-tetrahydro-1H-indazol-1-yl ) Biphenyl, 3,4'-bis (4,5,6,7-tetrahydro-1H-indazol-1-yl) biphenyl, 3,3'-bis (4,5,6,7-tetrahydro-1H-indazole) -1-yl) biphenyl, 1,4-bis (4- (4,5,6,7-tetrahydro-1H-indazol-1-yl) phenyl) benzene, 1,4-bis (4,5,6, 7-tetrahydroindol-1-yl) benzene, 1,3-bis (4,5,6,7-tetrahydroindol-1-yl) benzene, 4,4'-bis (4,5,6,7-tetrahydro Indol-1-yl) biphenyl, 3,4'-bis (4,5,6,7-tetrahydroindol-1-yl) biphenyl, 3,3'-bis (4,5,6,7-tetrahydroindole- 1-yl) biphenyl, 1,4-bis (4- (4,5,6,7-tetrahydroindol-1-yl) phenyl) benzene, 1,4-bis (4,5,6,7-tetrahydroiso Indol-2-yl) benzene, 1,3-bis (4,5,6,7-tetrahydroisoindol-2-yl) benzene, 4,4'-bis (4,5,6,7-tetrahi Droisoindol-2-yl) biphenyl, 3,4'-bis (4,5,6,7-tetrahydroisoindol-2-yl) biphenyl, 3,3'-bis (4,5,6,7- Tetrahydroisoindol-2-yl) biphenyl, 1,4-bis (4- (4,5,6,7-tetrahydroisoindol-2-yl) phenyl) benzene and the like, among them, for example, 4,5, 6,7-tetrahydroindole, 4,5,6,7-tetrahydroisoindole, 4,5,6,7-tetrahydroindene and the like are preferable.

  Preferable specific examples of the compound represented by the general formula [26] include, for example, 1,2,3,4-tetrahydroacridine, 1-methyl-1,2,3,4-tetrahydroacridine, 2-methyl-1,2 , 3,4-Tetrahydroacridine, 3-methyl-1,2,3,4-tetrahydroacridine, 4-methyl-1,2,3,4-tetrahydroacridine, 5-methyl-1,2,3,4- Tetrahydroacridine, 6-methyl-1,2,3,4-tetrahydroacridine, 7-methyl-1,2,3,4-tetrahydroacridine, 8-methyl-1,2,3,4-tetrahydroacridine, 9- Methyl-1,2,3,4-tetrahydroacridine, 1-ethyl-1,2,3,4-tetrahydroacridine, 2-ethyl-1,2,3,4-tetrahydroacridine, 3-ethyl-1,2 , 3,4-Tetrahydroacridine, 4-ethyl-1,2,3,4-tetrahydroacridine, 5-ethyl-1,2,3,4-tetrahydroacridine, 6-ethyl-1,2,3,4- Tetrahydroacridine, 7-ethyl-1,2,3,4- Torahydroacridine, 8-ethyl-1,2,3,4-tetrahydroacridine, 9-ethyl-1,2,3,4-tetrahydroacridine, 1-isopropyl-1,2,3,4-tetrahydroacridine, 2 -Isopropyl-1,2,3,4-tetrahydroacridine, 3-isopropyl-1,2,3,4-tetrahydroacridine, 4-isopropyl-1,2,3,4-tetrahydroacridine, 5-isopropyl-1, 2,3,4-tetrahydroacridine, 6-isopropyl-1,2,3,4-tetrahydroacridine, 7-isopropyl-1,2,3,4-tetrahydroacridine, 8-isopropyl-1,2,3,4 -Tetrahydroacridine, 9-isopropyl-1,2,3,4-tetrahydroacridine, 1-propyl-1,2,3,4-tetrahydroacridine, 2-propyl-1,2,3,4-tetrahydroacridine, 3 -Propyl-1,2,3,4-tetrahydroacridine, 4-propyl-1,2,3,4-tetrahydroacridine, 5-propyl-1,2,3,4-tetra Hydroacridine, 6-propyl-1,2,3,4-tetrahydroacridine, 7-propyl-1,2,3,4-tetrahydroacridine, 8-propyl-1,2,3,4-tetrahydroacridine, 9- Propyl-1,2,3,4-tetrahydroacridine, 1-tert-butyl-1,2,3,4-tetrahydroacridine, 2-tert-butyl-1,2,3,4-tetrahydroacridine, 3-tert -Butyl-1,2,3,4-tetrahydroacridine, 4-tert-butyl-1,2,3,4-tetrahydroacridine, 5-tert-butyl-1,2,3,4-tetrahydroacridine, 6- tert-butyl-1,2,3,4-tetrahydroacridine, 7-tert-butyl-1,2,3,4-tetrahydroacridine, 8-tert-butyl-1,2,3,4-tetrahydroacridine, 9 -tert-butyl-1,2,3,4-tetrahydroacridine, 1-amino-1,2,3,4-tetrahydroacridine, 2-amino-1,2,3,4-tetrahydroacridine, 3-amino- 1,2,3,4-tetrahydroacridine, 4-amino-1,2,3,4- Tetrahydroacridine, 5-amino-1,2,3,4-tetrahydroacridine, 6-amino-1,2,3,4-tetrahydroacridine, 7-amino-1,2,3,4-tetrahydroacridine, 8- Amino-1,2,3,4-tetrahydroacridine, 9-amino-1,2,3,4-tetrahydroacridine, 1-hydroxy-1,2,3,4-tetrahydroacridine, 2-hydroxy-1,2 , 3,4-Tetrahydroacridine, 3-hydroxy-1,2,3,4-tetrahydroacridine, 4-hydroxy-1,2,3,4-tetrahydroacridine, 5-hydroxy-1,2,3,4- Tetrahydroacridine, 6-hydroxy-1,2,3,4-tetrahydroacridine, 7-hydroxy-1,2,3,4-tetrahydroacridine, 8-hydroxy-1,2,3,4-tetrahydroacridine, 9- Hydroxy-1,2,3,4-tetrahydroacridine, 1,2,3,4-tetrahydroacridine-1-carboxylic acid, 1,2,3,4-tetrahydroacridine-2-carboxylic acid, 1, 2,3,4-tetrahydroacridine-3-carboxylic acid, 1,2,3,4-tetrahydroacridine-4-carboxylic acid, 1,2,3,4-tetrahydroacridine-5-carboxylic acid, 1,2, 3,4-tetrahydroacridine-6-carboxylic acid, 1,2,3,4-tetrahydroacridine-7-carboxylic acid, 1,2,3,4-tetrahydroacridine-8-carboxylic acid, 1,2,3, 4-tetrahydroacridine-9-carboxylic acid, 1-methoxy-1,2,3,4-tetrahydroacridine, 2-methoxy-1,2,3,4-tetrahydroacridine, 3-methoxy-1,2,3, 4-tetrahydroacridine, 4-methoxy-1,2,3,4-tetrahydroacridine, 5-methoxy-1,2,3,4-tetrahydroacridine, 6-methoxy-1,2,3,4-tetrahydroacridine, 7-methoxy-1,2,3,4-tetrahydroacridine, 8-methoxy-1,2,3,4-tetrahydroacridine, 9-methoxy-1,2,3,4-tetrahydroacridine, 1-benzyloxy- 1,2,3,4-te Lahydroacridine, 2-benzyloxy-1,2,3,4-tetrahydroacridine, 3-benzyloxy-1,2,3,4-tetrahydroacridine, 4-benzyloxy-1,2,3,4-tetrahydro Acridine, 5-benzyloxy-1,2,3,4-tetrahydroacridine, 6-benzyloxy-1,2,3,4-tetrahydroacridine, 7-benzyloxy-1,2,3,4-tetrahydroacridine, 8-benzyloxy-1,2,3,4-tetrahydroacridine, 9-benzyloxy-1,2,3,4-tetrahydroacridine, 1,2,3,4-tetrahydroanthracene, 1-methyl-1,2 , 3,4-Tetrahydroanthracene, 2-methyl-1,2,3,4-tetrahydroanthracene, 3-methyl-1,2,3,4-tetrahydroanthracene, 4-methyl-1,2,3,4- Tetrahydroanthracene, 5-methyl-1,2,3,4-tetrahydroanthracene, 6-methyl-1,2,3,4-tetrahydroanthracene, 7-methyl-1,2,3,4- Trahydroanthracene, 8-methyl-1,2,3,4-tetrahydroanthracene, 9-methyl-1,2,3,4-tetrahydroanthracene, 1-ethyl-1,2,3,4-tetrahydroanthracene, 2 -Ethyl-1,2,3,4-tetrahydroanthracene, 3-ethyl-1,2,3,4-tetrahydroanthracene, 4-ethyl-1,2,3,4-tetrahydroanthracene, 5-ethyl-1, 2,3,4-tetrahydroanthracene, 6-ethyl-1,2,3,4-tetrahydroanthracene, 7-ethyl-1,2,3,4-tetrahydroanthracene, 8-ethyl-1,2,3,4 -Tetrahydroanthracene, 9-ethyl-1,2,3,4-tetrahydroanthracene, 1-isopropyl-1,2,3,4-tetrahydroanthracene, 2-isopropyl-1,2,3,4-tetrahydroanthracene, 3 -Isopropyl-1,2,3,4-tetrahydroanthracene, 4-isopropyl-1,2,3,4-tetrahydroanthracene, 5-isopropyl-1,2,3,4-tetra Hydroanthracene, 6-isopropyl-1,2,3,4-tetrahydroanthracene, 7-isopropyl-1,2,3,4-tetrahydroanthracene, 8-isopropyl-1,2,3,4-tetrahydroanthracene, 9- Isopropyl-1,2,3,4-tetrahydroanthracene, 1-propyl-1,2,3,4-tetrahydroanthracene, 2-propyl-1,2,3,4-tetrahydroanthracene, 3-propyl-1,2 , 3,4-Tetrahydroanthracene, 4-propyl-1,2,3,4-tetrahydroanthracene, 5-propyl-1,2,3,4-tetrahydroanthracene, 6-propyl-1,2,3,4- Tetrahydroanthracene, 7-propyl-1,2,3,4-tetrahydroanthracene, 8-propyl-1,2,3,4-tetrahydroanthracene, 9-propyl-1,2,3,4-tetrahydroanthracene, 1- tert-butyl-1,2,3,4-tetrahydroanthracene, 2-tert-butyl-1,2,3,4-tetrahydroanthracene, 3-tert- Tyl-1,2,3,4-tetrahydroanthracene, 4-tert-butyl-1,2,3,4-tetrahydroanthracene, 5-tert-butyl-1,2,3,4-tetrahydroanthracene, 6-tert -Butyl-1,2,3,4-tetrahydroanthracene, 7-tert-butyl-1,2,3,4-tetrahydroanthracene, 8-tert-butyl-1,2,3,4-tetrahydroanthracene, 9- tert-butyl-1,2,3,4-tetrahydroanthracene, 1-amino-1,2,3,4-tetrahydroanthracene, 2-amino-1,2,3,4-tetrahydroanthracene, 3-amino-1 , 2,3,4-tetrahydroanthracene, 4-amino-1,2,3,4-tetrahydroanthracene, 5-amino-1,2,3,4-tetrahydroanthracene, 6-amino-1,2,3, 4-tetrahydroanthracene, 7-amino-1,2,3,4-tetrahydroanthracene, 8-amino-1,2,3,4-tetrahydroanthracene, 9-amino-1,2,3,4-tetrahydroanthracene, 1-hydroxy-1,2,3,4 -Tetrahydroanthracene, 2-hydroxy-1,2,3,4-tetrahydroanthracene, 3-hydroxy-1,2,3,4-tetrahydroanthracene, 4-hydroxy-1,2,3,4-tetrahydroanthracene, 5 -Hydroxy-1,2,3,4-tetrahydroanthracene, 6-hydroxy-1,2,3,4-tetrahydroanthracene, 7-hydroxy-1,2,3,4-tetrahydroanthracene, 8-hydroxy-1, 2,3,4-tetrahydroanthracene, 9-hydroxy-1,2,3,4-tetrahydroanthracene, 1,2,3,4-tetrahydroanthracene-1-carboxylic acid, 1,2,3,4-tetrahydroanthracene -2-carboxylic acid, 1,2,3,4-tetrahydroanthracene-3-carboxylic acid, 1,2,3,4-tetrahydroanthracene-4-carboxylic acid, 1,2,3,4-tetrahydroanthracene-5 -Carboxylic acid, 1,2,3,4-tetrahydroanthracene-6-carboxylic acid, 1,2,3,4-tetrahydroanthracene-7- Rubonic acid, 1,2,3,4-tetrahydroanthracene-8-carboxylic acid, 1,2,3,4-tetrahydroanthracene-9-carboxylic acid, 1-methoxy-1,2,3,4-tetrahydroanthracene, 2-methoxy-1,2,3,4-tetrahydroanthracene, 3-methoxy-1,2,3,4-tetrahydroanthracene, 4-methoxy-1,2,3,4-tetrahydroanthracene, 5-methoxy-1 , 2,3,4-tetrahydroanthracene, 6-methoxy-1,2,3,4-tetrahydroanthracene, 7-methoxy-1,2,3,4-tetrahydroanthracene, 8-methoxy-1,2,3, 4-tetrahydroanthracene, 9-methoxy-1,2,3,4-tetrahydroanthracene, 1-benzyloxy-1,2,3,4-tetrahydroanthracene, 2-benzyloxy-1,2,3,4-tetrahydro Anthracene, 3-benzyloxy-1,2,3,4-tetrahydroanthracene, 4-benzyloxy-1,2,3,4-tetrahydroanthracene, 5-ben Luoxy-1,2,3,4-tetrahydroanthracene, 6-benzyloxy-1,2,3,4-tetrahydroanthracene, 7-benzyloxy-1,2,3,4-tetrahydroanthracene, 8-benzyloxy- 1,2,3,4-tetrahydroanthracene, 9-benzyloxy-1,2,3,4-tetrahydroanthracene, etc., among which, for example, 1,2,3,4-tetrahydroacridine, 1,2,3 1,4-tetrahydroanthracene and the like are preferred.

  As the compound represented by the general formula [1], [2], [22] or [26], a commercially available product or a compound appropriately synthesized according to a conventional method may be used.

  Preferable specific examples of the deuterium compound represented by the general formula [6] include, for example, deuterated naphthalene, deuterated 1-aminonaphthalene, deuterated 2-aminonaphthalene, deuterated 1-methylnaphthalene, deuterium. 2-methylnaphthalene, deuterated 1-ethylnaphthalene, deuterated 2-ethylnaphthalene, deuterated 1-isopropylnaphthalene, deuterated 2-isopropylnaphthalene, deuterated 1-tert-butylnaphthalene, deuterium 2-tert-butylnaphthalene, deuterated 1-hydroxynaphthalene, deuterated 2-hydroxynaphthalene, deuterated naphthalene-1-carboxylic acid, deuterated naphthalene-2-carboxylic acid, deuterated quinoline, deuterated Hydrogenated 2-methylquinoline, deuterated 3-methylquinoline, deuterated 4-methylquinoline, deuterated 5-methylquinoline, deuterated 6-methylquinoline, deuterated 7-methylquinoline Norin, deuterated 8-methylquinoline, deuterated 2-ethylquinoline, deuterated 3-ethylquinoline, deuterated 4-ethylquinoline, deuterated 5-ethylquinoline, deuterated 6-ethylquinoline, Deuterated 7-ethyltetrahydroquinoline, deuterated 8-ethylquinoline, deuterated 2-isopropylquinoline, deuterated 3-isopropylquinoline, deuterated 4-isopropylquinoline, deuterated 5-isopropylquinoline, deuterated Hydrogenated 6-isopropylquinoline, deuterated 7-isopropylquinoline, deuterated 8-isopropylquinoline, deuterated 2-propylquinoline, deuterated 3-propylquinoline, deuterated 4-propylquinoline, deuterated 5-propylquinoline, deuterated 6-propylquinoline, deuterated 7-propylquinoline, deuterated 8-propylquinoline, deuterated 2-tert-butylquinoline, deuterated water 3-tert-butylquinoline, deuterated 4-tert-butylquinoline, deuterated 5-tert-butylquinoline, deuterated 6-tert-butylquinoline, deuterated 7-tert-butylquinoline, deuterium 8-tert-butylquinoline, deuterated 2-aminoquinoline, deuterated 3-aminoquinoline, deuterated 4-aminoquinoline, deuterated 2-hydroxyquinoline, deuterated 3-hydroxyquinoline, deuterium 4-hydroxyquinoline, deuterated quinoline-2-carboxylic acid, deuterated quinoline-3-carboxylic acid, deuterated quinoline-4-carboxylic acid, deuterated 2-methyl-8-hydroxyquinoline, deuterium 3-methyl-8-hydroxyquinoline, deuterated 4-methyl-8-hydroxyquinoline, deuterated 8-hydroxyquinoline-2-carboxylic acid, deuterated isoquinoline, deuterated 1-methylisoquinoline, deuterium 3-methylisoquinoline, deuterated 4-methyl Tilisoquinoline, deuterated 5-methylisoquinoline, deuterated 6-methylisoquinoline, deuterated 7-methylisoquinoline, deuterated 8-methylisoquinoline, deuterated 1-ethylisoquinoline, deuterated 3-ethylisoquinoline Deuterated 4-ethylisoquinoline, deuterated 5-ethylisoquinoline, deuterated 6-ethylisoquinoline, deuterated 7-ethylisoquinoline, deuterated 8-ethylisoquinoline, deuterated 2-isopropylisoquinoline, deuterated Hydrogenated 3-isopropylisoquinoline, deuterated 4-isopropylisoquinoline, deuterated 5-isopropylisoquinoline, deuterated 6-isopropylisoquinoline, deuterated 7-isopropylisoquinoline, deuterated 8-isopropylisoquinoline, deuterated 2-propylisoquinoline, deuterated 3-propylisoquinoline, deuterated 4-propi Isoquinoline, deuterated 5-propylisoquinoline, deuterated 6-propylisoquinoline, deuterated 7-propylisoquinoline, deuterated 8-propylisoquinoline, deuterated 1-tert-butylisoquinoline, deuterated 3-tert -Butylisoquinoline, deuterated 4-tert-butylisoquinoline, deuterated 5-tert-butylisoquinoline, deuterated 6-tert-butylisoquinoline, deuterated 7-tert-butylisoquinoline, deuterated 8-tert -Butylisoquinoline, deuterated 1-aminoisoquinoline, deuterated 3-aminoisoquinoline, deuterated 4-aminoisoquinoline, deuterated 1-hydroxyisoquinoline, deuterated 3-hydroxyisoquinoline, deuterated 4-hydroxy Isoquinoline, deuterated isoquinoline-1-carboxylic acid, deuterated isoquinoline-3-carboxylic acid, deuterated isoquinoline-4-carboxylic acid, deuterium 1,4-bis (isoquinolin-1-yl) benzene, deuterated 1,3-bis (isoquinolin-1-yl) benzene, deuterated 4,4 '-(isoquinolin-1-yl) biphenyl, deuterium 3,4 '-(isoquinolin-1-yl) biphenyl, deuterated 3,3'-(isoquinolin-1-yl) biphenyl, deuterated 1,4-bis (4- (isoquinolin-1-yl) Phenyl) benzene, deuterated 1,4-bis (quinolin-2-yl) benzene, deuterated 1,3-bis (quinolin-2-yl) benzene, deuterated 4,4'-bis (quinoline- 2-yl) biphenyl, deuterated 3,4'-bis (quinolin-2-yl) biphenyl, deuterated 3,3'-bis (quinolin-2-yl) biphenyl, deuterated 1,4-bis (4- (quinolin-2-yl) phenyl) benzene and the like. Among them, for example, deuterated naphthalene, deuterated 8-hydroxyquinoline-2-carboxylic acid, deuterated quino Phosphorus, deuterated isoquinoline and the like are preferable.

  Preferable specific examples of the deuterium compound represented by the general formula [7] include, for example, deuterated carbazole, deuterated 1-methylcarbazole, deuterated 2-methylcarbazole, deuterated 3-methylcarbazole, and deuterium. 4-methylcarbazole, deuterated 1-ethylcarbazole, deuterated 2-ethylcarbazole, deuterated 3-ethylcarbazole, deuterated 4-ethylcarbazole, deuterated 1-isopropylcarbazole, deuterated 2 -Isopropylcarbazole, deuterated 3-isopropylcarbazole, deuterated 4-isopropylcarbazole, deuterated 1-propylcarbazole, deuterated 2-propylcarbazole, deuterated 3-propylcarbazole, deuterated 4-propyl Carbazole, deuterated 1-tert-butylcarbazole, deuterated 2-tert-butylcarbazole, deuterated 3-tert -Butylcarbazole, deuterated 4-tert-butylcarbazole, deuterated 1-aminocarbazole, deuterated 2-aminocarbazole, deuterated 3-aminocarbazole, deuterated 4-aminocarbazole, deuterated 1 -Hydroxycarbazole, deuterated 2-hydroxycarbazole, deuterated 3-hydroxycarbazole, deuterated 4-hydroxycarbazole, deuterated carbazole-1-carboxylic acid, deuterated carbazole-2-carboxylic acid, deuterium Carbazole-3-carboxylic acid, deuterated carbazole-4-carboxylic acid, deuterated carbazole-5-carboxylic acid, deuterated carbazole-6-carboxylic acid, deuterated carbazole-7-carboxylic acid, deuterium Carbazole-8-carboxylic acid, deuterated 1-methoxycarbazole, deuterated 2-methoxycarbazole, deuterated 3-methoxycarbazol Deuterated 4-methoxycarbazole, deuterated 5-methoxycarbazole, deuterated 6-methoxycarbazole, deuterated 7-methoxycarbazole, deuterated 8-methoxycarbazole, deuterated 1-benzyloxy-carbazole Deuterated 2-benzyloxycarbazole, deuterated 3-benzyloxycarbazole, deuterated 4-benzyloxycarbazole, deuterated 5-benzyloxycarbazole, deuterated 6-benzyloxycarbazole, deuterated 7 -Benzyloxycarbazole, deuterated 8-benzyloxycarbazole, deuterated 1,4-bis (carbazol-9-yl) benzene, deuterated 1,3-bis (carbazol-9-yl) benzene, deuterium 3,4'-bis (carbazol-9-yl) biphenyl, deuterated 4,4'-bis (carbazol-9-yl) biphenyl, deuterated 1,4-biphenyl (4- (carbazol-9-yl) phenyl) benzene, deuterated 1- (3- (carbazol-9-yl) phenyl) -4- (4- (carbazol-9-yl) phenyl) benzene, deuterated Hydrogenated 1,4-bis (3- (carbazol-9-yl) phenyl) benzene, deuterated 4,4'-bis (carbazol-9-yl) biphenyl, deuterated fluorene, deuterated 1-methyl Fluorene, deuterated 2-methylfluorene, deuterated 3-methylfluorene, deuterated 4-methylfluorene, deuterated 9,9-dimethylfluorene, deuterated 1-ethylfluorene, deuterated 2-ethyl Fluorene, deuterated 3-ethylfluorene, deuterated 4-ethylfluorene, deuterated 9,9-diethylfluorene, deuterated 1-isopropyl-fluorene, deuterated 2-isopropylfluorene, deuterated 3- Isopropylfluorene, deuterated 4-isopropylfluorene Deuterated 1-propylfluorene, deuterated 2-propylfluorene, deuterated 3-propylfluorene, deuterated 4-propylfluorene, deuterated 9,9-dipropylfluorene, deuterated 1-tert- Butylfluorene, deuterated 2-tert-butylfluorene, deuterated 3-tert-butylfluorene, deuterated 4-tert-butylfluorene, deuterated 1-aminofluorene, deuterated 2-aminofluorene, deuterium Hydrogenated 3-aminofluorene, deuterated 4-aminofluorene, deuterated 9-aminofluorene, deuterated 1-hydroxyfluorene, deuterated 2-hydroxyfluorene, deuterated 3-hydroxyfluorene, deuterated 4-hydroxyfluorene, deuterated fluorene-1-carboxylic acid, deuterated fluorene-2-carboxylic acid, deuterated fluorene-3-carboxylic acid, deuterated fluorene-4-carboxylic acid, deuterated Hydrogenated 1-methoxyfluorene, deuterated 2-methoxyfluorene, deuterated 3-methoxyfluorene, deuterated 4-methoxyhydrofluorene, deuterated 1-benzyloxyfluorene, deuterated 2-benzyloxyfluorene, Examples include deuterated 3-benzyloxyfluorene and deuterated 4-benzyloxyfluorene. Among them, deuterated compounds such as deuterated carbazole and deuterated fluorene are preferable.

  Preferable specific examples of the compound represented by the general formula [28] include, for example, deuterated indole, deuterated 2-methylindole, deuterated 3-methylindole, deuterated 4-methylindole, deuterated 5 -Methylindole, deuterated 6-methylindole, deuterated 7-methylindole, deuterated 2-ethylindole, deuterated 3-ethylindole, deuterated 4-ethylindole, deuterated 5-ethyl Indole, deuterated 6-ethylindole, deuterated 7-ethylindole, deuterated 2-propylindole, deuterated 3-propylindole, deuterated 4-propylindole, deuterated 5-propylindole, Deuterated 6-propylindole, deuterated 7-propylindole, deuterated 2-isopropylhydroindole, deuterated 3-isopropylindole, deuterated 4-isopropylindole, deuterated 5-isopropylindole, deuterated 6-isopropylindole, deuterated 7-isopropylindole, deuterated 2-tert-butylindole, deuterated 3-tert-butylindole, deuterated Hydrogenated 4-tert-butylindole, deuterated 5-tert-butylindole, deuterated 6-tert-butylindole, deuterated 7-tert-butylindole, deuterated 2-aminoindole, deuterated 3-aminoindole, deuterated 2-hydroxyindole, deuterated 3-hydroxyindole, deuterated indole-2-carboxylic acid, deuterated indole-3-carboxylic acid, deuterated isoindole, deuterated 1-methylisoindole, deuterated 3-methylhydroisoindole, deuterated 4-methyltetrahydroisoindole, deuterated 5-methylisoindole, deuterated 6 -Methylisoindole, deuterated 7-methylisoindole, deuterated 1-ethylisoindole, deuterated 3-ethylisoindole, deuterated 4-ethylisoindole, deuterated 5-ethylisoindole, Deuterated 6-ethylisoindole, deuterated 7-ethylisoindole, deuterated 1-propylisoindole, deuterated 3-propylisoindole, deuterated 4-propylisoindole, deuterated 5- Propylisoindole, deuterated 6-propylisoindole, deuterated 7-propylisoindole, deuterated 1-isopropylisoindole, deuterated 3-isopropylisoindole, deuterated 4-isopropylisoindole, deuterated Hydrogenated 5-isopropylisoindole, deuterated 6-isopropylisoindole, deuterated 7-isopropylisoindole, Hydrogenated 1-tert-butylisoindole, deuterated 3-tert-butylisoindole, deuterated 4-tert-butylisoindole, deuterated 5-tert-butylisoindole, deuterated 6-tert- Butyl isoindole, deuterated 7-tert-butylisoindole, deuterated 1-aminoisoindole, deuterated 3-aminoisoindole, deuterated 1-hydroxyisoindole, deuterated 3-hydroxyisoindole , Deuterated isoindole-1-carboxylic acid, deuterated isoindole-3-carboxylic acid, deuterated indene, deuterated 2-methylindene, deuterated 3-methylindene, deuterated 4-methyl Indene, deuterated 5-methylindene, deuterated 6-methylindene, deuterated 7-methylindene, deuterated 2-ethylindene, deuterated 3-ethylindene, deuterated 4-ethylindene, Deuteration 5-ethylindene, deuterated 6-ethylindene, deuterated 7-ethylindene, deuterated 2-propylindene, deuterated 3-propylindene, deuterated 4-propylindene, deuterated 5- Propylindene, deuterated 6-propylindene, deuterated 7-propylindene, deuterated 2-isopropylindene, deuterated 3-isopropylindene, deuterated 4-isopropylindene, deuterated 5-isopropylindene Deuterated 6-isopropylindene, deuterated 7-isopropylindene, deuterated 2-tert-butylindene, deuterated 3-tert-butylindene, deuterated 4-tert-butylindene, deuterated 5-tert-butylindene, deuterated 6-tert-butylindene, deuterated 7-tert-butylindene, deuterated 2-aminoindene, deuterated 3-aminoindene, deuterated 2-hydroxyindene , Deuterated 3-hydroxyindene, deuterated inden-2-carboxylic acid, deuterated inden-3-carboxylic acid, deuterated 1,4-bis (1H-indazol-1-yl) benzene, deuterium 1,3-bis (1H-indazol-1-yl) benzene, deuterated 4,4'-bis (1H-indazol-1-yl) biphenyl, deuterated 3,4'-bis (1H-indazole) -1-yl) biphenyl, deuterated 3,3′-bis (1H-indazol-1-yl) biphenyl, deuterated 4,4′-bis (4- (1H-indazol-1-yl) phenyl) Benzene, deuterated 1,4-bis (indol-1-yl) benzene, deuterated 1,3-bis (indol-1-yl) benzene, deuterated 4,4'-bis (indole-1- Yl) biphenyl, deuterated 3,4'-bis (indol-1-yl) biphenyl, deuterated 3,3'-bis (indol-1-yl) biphenyl, deuterated 1,4-bis (4 - Indol-1-yl) phenyl) benzene, deuterated 1,4-bis (isoindol-2-yl) benzene, deuterated 1,3-bis (isoindol-2-yl) benzene, deuterated 4 , 4'-bis (isoindol-2-yl) biphenyl, deuterated 3,4'-bis (isoindol-2-yl) biphenyl, deuterated 3,3'-bis (isoindol-2-yl) ) Biphenyl, deuterated 1,4-bis (4- (isoindol-2-yl) phenyl) benzene, etc., among which deuterated indole, deuterated isoindole, deuterated indene, etc. preferable.

  Preferable specific examples of the compound represented by the general formula [32] include, for example, deuterated acridine, deuterated 1-methylacridine, deuterated 2-methylacridine, deuterated 3-methylacridine, deuterated 4 -Methyl acridine, deuterated 9-methyl acridine, deuterated 1-ethyl acridine, deuterated 2-ethyl acridine, deuterated 3-ethyl acridine, deuterated 4-ethyl acridine, deuterated 9-ethyl Acridine, deuterated 1-isopropyl acridine, deuterated 2-isopropyl acridine, deuterated 3-isopropyl acridine, deuterated 4-isopropyl acridine, deuterated 9-isopropyl acridine, deuterated 1-propyl acridine, Deuterated 2-propylacridine, deuterated 3-propylacridine, deuterated 4-propylacridine, deuterated 9-propylacridine , Deuterated 1-tert-butyl acridine, deuterated 2-tert-butyl acridine, deuterated 3-tert-butyl acridine, deuterated 4-tert-butyl acridine, deuterated 9-tert-butyl acridine Deuterated 1-aminoacridine, deuterated 2-aminoacridine, deuterated 3-aminoacridine, deuterated 4-aminoacridine, deuterated 9-aminoacridine, deuterated 1-hydroxyacridine, deuterated Hydrogenated 2-hydroxyacridine, deuterated 3-hydroxyacridine, deuterated 4-hydroxyacridine, deuterated 9-hydroxyacridine, deuterated acridine-1-carboxylic acid, deuterated acridine-2-carboxylic acid , Deuterated acridine-3-carboxylic acid, deuterated acridine-4-carboxylic acid, deuterated acridine-9-carboxylic acid, deuterated 1-methoxyacridine, deuterated 2-methoxyacridine Deuterated 3-methoxyacridine, deuterated 4-methoxyacridine, deuterated 9-methoxyacridine, deuterated 1-benzyloxyacridine, deuterated 2-benzyloxyacridine, deuterated 3-benzyloxyacridine Deuterated 4-benzyloxyacridine, deuterated 9-benzyloxyacridine, deuterated anthracene, deuterated 1-methylanthracene, deuterated 2-methylanthracene, deuterated 3-methylanthracene, deuterium 4-methylanthracene, deuterated 9-methylanthracene, deuterated 1-ethylanthracene, deuterated 2-ethylanthracene, deuterated 3-ethylanthracene, deuterated 4-ethylanthracene, deuterated 9 -Ethylanthracene, deuterated 1-isopropylanthracene, deuterated 2-isopropylanthracene, deuterated 3-isopropyl Pyranthracene, deuterated 4-isopropylanthracene, deuterated 9-isopropylanthracene, deuterated 1-propylanthracene, deuterated 2-propylanthracene, deuterated 3-propylanthracene, deuterated 4-propylanthracene Deuterated 9-propylanthracene, deuterated 1-tert-butylanthracene, deuterated 2-tert-butylanthracene, deuterated 3-tert-butylanthracene, deuterated 4-tert-butylanthracene, deuterated Hydrogenated 9-tert-butylanthracene, deuterated 1-aminoanthracene, deuterated 2-aminoanthracene, deuterated 3-aminoanthracene, deuterated 4-aminoanthracene, deuterated 9-aminoanthracene, deuterated Hydrogenated 1-hydroxyanthracene, Deuterated 2-hydroxyanthracene, Deuterated 3-hydroxyanthracene, Deuterated 4-H Droxyanthracene, deuterated 9-hydroxyanthracene, deuterated anthracene-1-carboxylic acid, deuterated anthracene-2-carboxylic acid, deuterated anthracene-3-carboxylic acid, deuterated anthracene-4-carboxylic acid Acid, deuterated anthracene-9-carboxylic acid, deuterated 1-methoxyanthracene, deuterated 2-methoxyanthracene, deuterated 3-methoxyanthracene, deuterated 4-methoxyanthracene, deuterated 9-methoxy Anthracene, deuterated 1-benzyloxyanthracene, deuterated 2-benzyloxyanthracene, deuterated 3-benzyloxyanthracene, deuterated 4-benzyloxyanthracene, deuterated 9-benzyloxyanthracene, deuterated Examples include acridine and deuterated anthracene.

In the deuteration method of the present invention, the deuterated solvent used may be, for example, deuterium (D ₂ O), such as deuterium, deuterium, deuterium, deuterium, when deuterium is deuterium. Heavy alcohols such as heavy butanol, heavy tert-butanol, heavy pentanol, heavy hexanol, heavy heptanol, heavy octanol, heavy nonanol, heavy decanol, heavy undecanol, heavy dodecanol, such as heavy formic acid, heavy acetic acid, heavy propionic acid, Heavy carboxylic acids such as heavy butyric acid, heavy isobutyric acid, heavy valeric acid, heavy isovaleric acid, heavy pivalic acid, such as heavy acetone, heavy methyl ethyl ketone, heavy methyl isobutyl ketone, heavy diethyl ketone, heavy dipropyl ketone, heavy diisopropyl ketone, heavy Deuterated heavy ketones such as dibutyl ketone and deuterated dimethyl sulfoxide Among them, heavy water and heavy alcohols are preferable, and specifically, heavy water and heavy methanol are particularly preferable. In view of the environment and workability, heavy water is preferable. In addition, examples of the deuterated solvent when deuterium is tritium include heavy water (T ₂ O). These may be used alone or in combination of two or more.

  The deuterated solvent may be any solvent in which one or more hydrogen atoms in the molecule are deuterated. For example, a hydrogen atom of a hydroxyl group in heavy alcohols, a hydrogen atom of a carboxyl group in heavy carboxylic acids. If is deuterated, it can be used in the deuteration method of the present invention, but it is particularly preferred that all hydrogen atoms in the molecule are deuterated.

  The greater the amount of deuterated solvent used, the easier the deuteration of the present invention proceeds, but considering the economic aspect, the amount of deuterium atoms contained in the deuterated solvent is General formula [6], [7], [28] or obtained by dehydrogenating a compound (substrate) represented by general formula [1], [2], [22] or [26] according to the invention The lower limit for the deuterated hydrogen atom of the light hydride corresponding to the compound represented by [32] is preferably as a lower limit in order, equimolar, 10 times mole, 20 times mole, 30 times mole, 40 times mole, The amount is preferably 60 times the mole and the upper limit in order, and the amount is 250 times the mole, 150 times the mole, and 100 times the mole.

  In the deuteration method of the present invention, a reaction solvent may be used as necessary. However, it is usually unnecessary to use a reaction solvent if the reaction substrate is a liquid, and the reaction substrate is a solid. However, since a deuterated solvent is used as the deuterium source, the reaction solvent need not be used.

  As the reaction solvent used as necessary, since the deuteration of the present invention may be in a suspension state, it is possible to use a reaction solvent that is difficult to dissolve the substrate, but the substrate is dissolved. What is easy to do is more preferable. Specific examples of the reaction solvent include ethers such as dimethyl ether, diethyl ether, diisopropyl ether, ethyl methyl ether, tert-butyl methyl ether, 1,2-dimethoxyethane, oxirane, 1,4-dioxane, dihydropyran, and tetrahydrofuran. Aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, cyclohexane, such as methanol, ethanol, isopropanol, butanol, tert-butanol, pentanol, hexanol, heptanol, octanol, nonanol, decanol, undecanol, Alcohols such as dodecanol, for example carboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, pivalic acid, such as acetone, methyl ethyl ketone, methyl Ketone, diethyl ketone, dipropyl ketone, diisopropyl ketone and dibutyl ketone, dimethyl sulfoxide and the like.

  The deuteration method of the present invention may be carried out in the presence of hydrogen gas in the reaction system in order to promote the deuteration reaction. In the deuteration method of the present invention, a substrate dehydrogenation reaction and a deuteration reaction are simultaneously performed. Therefore, when deuterating a substrate in which the deuteration reaction proceeds faster than the dehydrogenation reaction, it is preferable to coexist hydrogen gas in the reaction system.

  When the deuteration method of the present invention is performed in the presence of hydrogen gas, the gas phase portion of the deuteration reaction vessel can be hydrogen gas (light hydrogen gas or deuterium gas, which can be used for promoting the reaction. The same applies hereinafter. However, it may be replaced with a mixed gas of hydrogen gas and an inert gas such as nitrogen or argon.

  When hydrogen gas is used in the deuteration method of the present invention, the amount used is represented by the general formula [1], [2], [22] or [26] according to the present invention used as a reaction substrate. With respect to the compound to be obtained, it is preferably in order as a lower limit, equimolar, 10-fold mole, 20-fold mole, 30-fold mole, and preferably in order as an upper limit, 100-fold mole and 40-fold mole.

  In the case of using hydrogen gas in the deuteration method of the present invention, it is preferable that the reaction vessel be sealed or close to it so that hydrogen gas is not dissipated. The state close to sealing includes a case where a reaction substrate is continuously charged into a reaction vessel and a product is continuously taken out, for example, as in a so-called continuous reaction.

  Examples of the palladium catalyst used as the catalyst used in the deuteration method of the present invention include those having a palladium valence of 0 to 4, preferably 0 to 2, and more preferably 0.

  As a platinum catalyst, the valence of a platinum atom is usually 0 to 4, preferably 0 to 2, more preferably 0.

  As a nickel catalyst, the valence of a nickel atom is usually 0 to 2, preferably 0.

  As a cobalt catalyst, the valence of a cobalt atom is usually 0 or monovalent.

  Examples of the iridium catalyst include those in which the valence of the iridium atom is generally 0 to 4, preferably 0 to 3, and more preferably 0.

  Examples of the rhodium catalyst include those having a valence of a rhodium atom of generally 0 to 4, preferably 0.

  Examples of the ruthenium catalyst include those in which the valence of the ruthenium atom is usually 0 to 4, preferably 0.

  In the case of palladium, platinum, nickel, cobalt, iridium, rhodium and ruthenium, the catalyst as described above may be a metal itself (metal simple substance) or a hydroxide, oxide, halide or acetate of the metal, In the case of palladium, platinum, nickel, cobalt and iridium, the following ligands may be coordinated. Among these, a metal catalyst in which a ligand is not coordinated, such as a simple metal, its hydroxide, oxide, halide, acetate, etc. is preferable. These metals (metal simple substance), metal hydroxides, metal oxides, metal halides, acetates or metal complexes may be supported on various carriers.

Examples of the ligand of the metal catalyst with which the ligand may be coordinated include 1,5-cyclooctadiene (COD), dibenzylideneacetone (DBA), bipyridine (BPY), phenanthroline (PHE), benzoate. Nitrile (PhCN), isocyanide (RNC), triethylarsine (As (Et) ₃ ), acetylacetonate (acac), pentamethylcyclopentadienyl (Cp *), ethylenediamine (EN) such as dimethylphenylphosphine (P ( CH ₃ ) ₂ Ph), diphenylphosphinoferrocene (DPPF), trimethylphosphine (P (CH ₃ ) ₃ ), triethylphosphine (PEt ₃ ), tritert-butylphosphine (P ^t Bu ₃ ), tricyclohexylphosphine (PCy) ₃ ), trimethoxyphosphine (P (OCH ₃ ) ₃ ), triethoxyphosphine (P (OEt) ₃ ), tritert-butoxyphosphine (P (O ^t Bu) ₃ ), triphenylphosphine (PPh ₃ ), 1 , 2-bis (diphenylphosphino And organic phosphine ligands such as ethane (DPPE), triphenoxyphosphine (P (OPh) ₃ ), and tri-o-tolylphosphine (P (o-tolyl) ₃ ).

Specific examples of the palladium metal catalyst include, for example, palladium hydroxide catalysts such as Pd, for example Pd (OH) ₂ , palladium oxide catalysts such as PdO, for example, palladium halide catalysts such as PdBr ₂ , PdCl ₂ , PdI _2, etc. Palladium acetate catalysts such as palladium acetate (Pd (OAc) ₂ ), palladium trifluoroacetate (Pd (OCOCF ₃ ) ₂ ), such as Pd (RNC) ₂ Cl ₂ , Pd (acac) ₂ , diacetate bis (triphenyl) Phosphine) palladium [Pd (OAc) ₂ (PPh ₃ ) ₂ ], Pd (PPh ₃ ) ₄ , Pd ₂ (dba) ₃ , Pd (NH ₃ ) ₂ Cl ₂ , Pd (CH ₃ CN) ₂ Cl ₂ , Dichlorobis (Benzonitrile) palladium [Pd (PhCN) ₂ Cl ₂ ], Pd (dppe) Cl ₂ , Pd (dppf) Cl ₂ , Pd (PCy ₃ ) ₂ Cl ₂ , Pd (PPh ₃ ) ₂ Cl ₂ , Pd [P (o-tolyl) ₃ ] ₂ Cl ₂ , Pd (cod) ₂ Cl ₂ , Pd (PPh ₃ ) (CH ₃ CN) ₂ Cl ₂ , Pd (en), etc. Examples include complex catalysts.

Specific examples of the platinum metal catalyst include platinum oxide catalysts such as Pt, for example PtO ₂ , platinum halide catalysts such as PtCl ₄ , PtCl ₂ , K ₂ PtCl ₄ , such as PtCl ₂ (cod), PtCl ₂ (dba ), PtCl ₂ (PCy ₃ ) ₂ , PtCl ₂ (P (OEt) ₃ ) ₂ , PtCl ₂ (P (O ^t Bu) ₃ ) ₂ , PtCl ₂ (bpy), PtCl ₂ (phe), Pt (PPh ₃ ) ₄ , Pt (cod) ₂ , Pt (dba) ₂ , Pt (bpy) ₂ , Pt (phe) _2, etc.

Specific examples of the nickel metal catalyst such as Ni, for example, nickel oxide catalyst such as NiO, for example, NiCl ₂ or the like halogenated nickel catalysts, for example, _{NiCl 2 (dppe), NiCl 2} (PPh 3) 2, Ni (PPh 3) ₄ , Ni (P (OPh) ₃ ) ₄ , Ni (cod) _{2 and the} like, and nickel metal complex catalysts coordinated to the ligand.

Specific examples of the cobalt metal catalyst include cobalt metal complex catalysts coordinated to a ligand such as Co (C ₃ H ₅ ) {P (OCH ₃ ) ₃ } ₃ .

Specific examples of the iridium metal catalyst include, for example, Ir, for example, Ir (cod) (acac), Cp * (P (CH ₃ ) ₃ ) IrCl _{2, and the} like, such as an iridium metal complex catalyst coordinated to a ligand. Can be mentioned.

  Examples of rhodium-based metal catalysts include Rh.

  Specific examples of the ruthenium metal catalyst include Ru.

  Examples of the carrier in the case where the metal catalyst as described above is supported on a carrier include carbon, alumina, silica gel, zeolite, molecular sieve, ion exchange resin, polymer, and the like. Among them, for example, carbon, alumina, etc. In particular, carbon is more preferable.

  The ion exchange resin used as the carrier is not particularly limited as long as it does not adversely affect the deuteration of the present invention, and examples thereof include a cation exchange resin and an anion exchange resin.

  Examples of the cation exchange resin include a weak acid cation exchange resin and a strong acid cation exchange resin. Examples of the anion exchange resin include a weak base anion exchange resin and a strong base anion exchange resin. Can be mentioned.

  The ion exchange resin generally contains a polymer cross-linked with a bifunctional monomer as a backbone polymer, to which an acidic group or a basic group is bonded, and each is exchanged with various cations or anions (counterions). .

  Specific examples of the weakly acidic cation exchange resin include those obtained by hydrolyzing an acrylic ester or methacrylic ester polymer crosslinked with divinylbenzene.

  Specific examples of the strongly acidic cation exchange resin include a sulfonated styrene-divinylbenzene copolymer.

  Examples of the strongly basic anion exchange resin include those in which an amino group is bonded to the aromatic ring of a styrene-divinylbenzene copolymer.

  The basic strength of basic anion exchange resins increases in order as the bound amino group becomes a primary amino group, secondary amino group, tertiary amino group, and quaternary ammonium salt. Become.

  A commercially available ion exchange resin can also be used as a catalyst carrier in the deuteration method of the present invention in the same manner as the above ion exchange resin.

The polymer used as the carrier is not particularly limited as long as it does not adversely affect the deuteration method of the present invention. Examples of such a polymer include a monomer represented by the general formula [21]. Examples thereof include those obtained by polymerization or copolymerization.

Wherein R ²⁷ represents a hydrogen atom, a lower alkyl group, a carboxyl group, a carboxyalkyl group, an alkoxycarbonyl group, a hydroxyalkoxycarbonyl group, a cyano group or a formyl group, and R ²⁸ represents a hydrogen atom, a lower alkyl group or a carboxyl group. Represents an alkoxycarbonyl group, a hydroxyalkoxycarbonyl group, a cyano group or a halogen atom, and R ²⁹ represents a hydrogen atom, a lower alkyl group, a haloalkyl group, a hydroxyl group, an aryl group which may have a substituent, an aliphatic heterocycle Group, aromatic heterocyclic group, halogen atom, alkoxycarbonyl group, hydroxyalkoxycarbonyl group, sulfo group, cyano group, cyanoalkyl group, acyloxy group, carboxyl group, carboxyalkyl group, aldehyde group, amino group, aminoalkyl group , Carbamoy Group, N- represents alkylcarbamoyl group or a hydroxyalkyl group, also bonded to the R ²⁷ and R ^28, together with the adjacent -C = C-may form an aliphatic ring.)

In the general formula [21], the lower alkyl group represented by R ^{27 to} R ²⁹ may be linear, branched or cyclic, and examples thereof include an alkyl group having 1 to 6 carbon atoms. Specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, sec-butyl group, n-pentyl group, isopentyl group, sec-pentyl group Tert-pentyl group, neopentyl group, 1-methylpentyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, neohexyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc. Can be mentioned.

Examples of the carboxyalkyl group represented by R ²⁷ and R ²⁹ include those in which a part of hydrogen atoms of the lower alkyl group as described above is substituted with a carboxyl group, and specific examples include a carboxymethyl group, a carboxy group, and the like. Examples thereof include an ethyl group, a carboxypropyl group, a carboxybutyl group, a carboxypentyl group, and a carboxyhexyl group.

As the alkoxycarbonyl group represented by R ^{27 to} R ²⁹ , for example, those having 2 to 11 carbon atoms are preferable, and specifically, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, a butoxycarbonyl group, a pentyloxycarbonyl group. Hexyloxycarbonyl group, cyclohexyloxycarbonyl group, heptyloxycarbonyl group, 2-ethylhexyloxycarbonyl group, octyloxycarbonyl group, nonyloxycarbonyl group, decyloxycarbonyl group and the like.

The hydroxyalkoxy group represented by R ²⁷ to R ^29, which some of the hydrogen atoms of the alkoxycarbonyl group having 2 to 11 carbon atoms such as described above is replaced by a hydroxyl group, specifically, For example, hydroxymethoxycarbonyl group, hydroxyethoxycarbonyl group, hydroxypropoxycarbonyl group, hydroxybutoxycarbonyl group, hydroxypentyloxycarbonyl group, hydroxyhexyloxycarbonyl group, hydroxyheptyloxycarbonyl group, hydroxyoctyloxycarbonyl group, hydroxynonyloxycarbonyl group And a hydroxydecyloxycarbonyl group.

Examples of the halogen atom represented by R ²⁸ and R ²⁹ include fluorine, chlorine, bromine, iodine and the like.

As the haloalkyl group represented by R ²⁹ , for example, part or all of the hydrogen atoms in the lower alkyl group represented by R ^{27 to} R ²⁹ are halogenated (for example, fluorinated, chlorinated, brominated, iodinated). Etc.), specifically, for example, chloromethyl group, bromomethyl group, trifluoromethyl group, 2-chloroethyl group, 3-chloropropyl group, 3-bromopropyl group 3,3,3-trifluoropropyl group, 4-chlorobutyl group, 5-chloropentyl group, 6-chlorohexyl group and the like.

  Examples of the aryl group of the aryl group which may have a substituent include a phenyl group, a tolyl group, a xylyl group, a naphthyl group, and the like. Examples of the substituent include an amino group, a hydroxyl group, and a lower alkoxy group. And carboxyl group.

  The lower alkoxy group mentioned as a substituent may be linear, branched or cyclic, and usually includes those having 1 to 6 carbon atoms. Specific examples include a methoxy group, an ethoxy group, and n-propoxy. Group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-pentyloxy group, isopentyloxy group, sec-pentyloxy group, tert-pentyloxy group, neopentyloxy Group, n-hexyloxy group, isohexyloxy group, sec-hexyloxy group, tert-hexyloxy group, neohexyloxy group, cyclopropoxy group, cyclobutoxy group, cyclopentyloxy group, cyclohexyloxy group and the like.

  Specific examples of the substituted aryl group include aminophenyl group, toluidino group, hydroxyphenyl group, methoxyphenyl group, tert-butoxyphenyl group, carboxyphenyl group and the like.

  Examples of the aliphatic heterocyclic group include a 5-membered ring or a 6-membered ring, and examples thereof include those containing 1 to 3 heteroatoms such as a nitrogen atom, an oxygen atom, and a sulfur atom. Examples thereof include 2-oxopyrrolidyl group, piperidyl group, piperidino group, piperazinyl group, morpholino group and the like.

  Examples of the aromatic heterocyclic group include a 5-membered ring or a 6-membered ring, and examples include those containing 1 to 3 heteroatoms such as a nitrogen atom, an oxygen atom, and a sulfur atom. For example, pyridyl group, imidazolyl group, thiazolyl group, furyl group, pyranyl group and the like can be mentioned.

Examples of the cyanoalkyl group include those in which a part of the hydrogen atoms of the lower alkyl group represented by R ^{27 to} R ²⁹ are substituted with a cyano group. Specific examples include a cyanomethyl group and 2-cyanoethyl group. Group, 2-cyanopropyl group, 3-cyanopropyl group, 2-cyanobutyl group, 4-cyanobutyl group, 5-cyanopentyl group, 6-cyanohexyl group and the like.

  Examples of the acyloxy group include those derived from a carboxylic acid having 2 to 20 carbon atoms. Specific examples include an acetyloxy group, a propionyloxy group, a butyryloxy group, a pentanoyloxy group, a nonanoyloxy group, and a decanoyloxy group. And benzoyloxy group.

Examples of the aminoalkyl group include those in which a part of the hydrogen atoms of the lower alkyl group represented by R ^{27 to} R ²⁹ is substituted with an amino group. Specific examples include an aminomethyl group, an aminoethyl group, Examples include aminopropyl group, aminobutyl group, aminopentyl group, aminohexyl group and the like.

  Examples of the N-alkylcarbamoyl group include those in which a part of hydrogen atoms of the carbamoyl group is substituted with an alkyl group. Specific examples include N-methylcarbamoyl group, N-ethylcarbamoyl group, Nn-propylcarbamoyl group. Group, N-isopropylcarbamoyl group, Nn-butylcarbamoyl group, N-tert-butylcarbamoyl group and the like.

  Examples of the hydroxyalkyl group include those in which a part of the hydrogen atoms of the lower alkyl group as described above is substituted with a hydroxyl group. Specifically, for example, a hydroxymethyl group, a hydroxyethyl group, a hydroxypropyl group, a hydroxybutyl group, and the like. Group, hydroxypentyl group, hydroxyhexyl group and the like.

Examples of the aliphatic ring formed by combining R ²⁷ and R ²⁸ together with the adjacent —C═C— include, for example, an unsaturated aliphatic ring having 5 to 10 carbon atoms. It may be a ring or a polycycle. Specific examples of these rings include a norbornene ring, a cyclopentene ring, a cyclohexene ring, a cyclooctene ring, a cyclodecene ring, and the like.

  Specific examples of the monomer represented by the general formula [21] include, for example, ethylenically unsaturated aliphatic hydrocarbons having 2 to 20 carbon atoms such as ethylene, propylene, butylene and isobutylene, such as styrene, 4-methylstyrene, 4 An ethylenically unsaturated aromatic hydrocarbon having 8 to 20 carbon atoms such as ethylstyrene and divinylbenzene, for example, an alkenyl ester having 3 to 20 carbon atoms such as vinyl formate, vinyl acetate, vinyl propionate, and isopropenyl acetate; For example, halogen-containing ethylenically unsaturated compounds having 2 to 20 carbon atoms such as vinyl chloride, vinylidene chloride, vinylidene fluoride, tetrafluoroethylene, such as acrylic acid, methacrylic acid, itaconic acid, maleic acid, fumaric acid, crotonic acid, C3-C20 ethylenic unsaturation such as vinyl acetate, allyl acetate, vinyl benzoate, etc. Carboxylic acids (these acids may be in the form of salts such as alkali metal salts and ammonium salts such as sodium and potassium), for example, methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate , 2-ethylhexyl methacrylate, methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, 2-ethylhexyl acrylate, lauryl methacrylate, stearyl acrylate, methyl itaconate, ethyl itaconate, methyl maleate, male Ethylenically unsaturated carboxylic acid esters such as ethyl acrylate, methyl fumarate, ethyl fumarate, methyl crotonic acid, ethyl crotonic acid, and methyl 3-butenoate, for example, 3 carbon atoms such as acrylonitrile, methacrylonitrile, allyl cyanide, etc. ~ 2 Cyanoethylenically unsaturated compounds such as acrylamide, methacrylamide, etc., such as C3-20 ethylenically unsaturated amides, such as acrolein, crotonaldehyde, etc. C2-C20 ethylenically unsaturated sulfonic acids such as vinylsulfonic acid and 4-vinylbenzenesulfonic acid (these acids are in the form of salts such as alkali metal salts such as sodium and potassium) For example, vinylamine, allylamine and the like, for example, ethylenically unsaturated aliphatic amines having 2 to 20 carbon atoms, such as vinylaniline, for example, ethylenically unsaturated aromatic amines such as N- C5-C20 ethylenically unsaturated aliphatic heterocyclic such as vinylpyrrolidone and vinylpiperidine Min, such allyl alcohol, ethylenically unsaturated alcohols having 3 to 20, such as crotyl alcohol, such as 4-vinylphenol ethylenically unsaturated phenols having 8 to 20 carbon atoms such as and the like.

  In the catalyst supported on the carrier, the proportion of palladium, platinum, nickel, cobalt, iridium, rhodium or ruthenium as the catalyst metal is usually 1 to 99% by weight, preferably 1 to 50% by weight, more preferably Is 1 to 30% by weight, more preferably 1 to 20% by weight, and particularly preferably 5 to 10% by weight.

  In the deuteration method of the present invention, the above-described catalysts may be used singly or in combination of two or more.

  In the deuteration method of the present invention, among the carrier-supported metal catalysts as described above, a palladium catalyst, a platinum catalyst or a mixed catalyst thereof is preferable, and among them, palladium carbon, platinum carbon or a mixed catalyst thereof is more preferable, In particular, a mixed catalyst of palladium carbon and platinum carbon is even more preferable.

  The catalyst mixing ratio in the case of using a mixture of two or more of the catalysts according to the present invention may be mixed at any ratio, but is preferably 1:99 to 99: 1, more preferably 1: 9 to 9: 1.

  For example, when a mixed catalyst of a palladium catalyst and a platinum catalyst is used, the mixing ratio is usually 1:99 to 99: 1, preferably 1: 9 to 9: 1 as a metal amount. Good. Furthermore, for example, when a mixed catalyst composed of palladium carbon and platinum carbon is used, the metal weight ratio of the palladium metal amount of palladium carbon to the platinum metal amount of platinum carbon is usually 1:99 to 99: 1, preferably What is necessary is just to mix so that it may become 1: 9-9: 1, More preferably, it is 1: 5-5: 1, More preferably, it is 1: 2-2: 1, Most preferably, it is 1: 1.

  When the deuteration of the present invention is performed using the mixed catalyst, the deuteration rate of the target product is improved as compared with the case where a single catalyst is used.

  The amount of the catalyst used in the deuteration method of the present invention is the same regardless of whether it is supported on a support or the like (that is, when the metal catalyst is supported on a support or the like, it is supported on the support). In terms of the weight in the state), based on the deuterated solvent as the deuterium source, usually a so-called catalytic amount, and then preferably 0.01 to 200% by weight, 0.01 to 100% by weight, 0.01 to 50% by weight, 0.01 to The amount is 20% by weight, 0.1-20% by weight, 1-20% by weight, 5-20% by weight. Further, the upper limit of the amount of catalyst metal contained in the whole catalyst is preferably 20% by weight, 10% by weight, 5% by weight and 2% by weight in order, and the lower limit is preferably 0.0005% by weight, 0.005% by weight and 0.05% by weight in order. % And 0.5% by weight.

  The amount of deuterated solvent used in the deuteration method of the present invention increases as the deuterated rate of the resulting deuterated product increases. However, considering the economical aspect, the substrate to be used On the other hand, the lower limit is usually 1 mol, preferably in order, preferably 2 mol, 3 mol, and the upper limit is usually 50 mol, preferably 40 mol, 30 mol, 20 mol, 10 mol, 5 moles.

  The reaction pressure at the time of carrying out the deuteration method of the present invention is usually 2 atm in the lower limit, more preferably 3 atm, 4 atm, 5 atm, and the upper limit is usually 100 atm, more preferably in the order 50 atm, 30 atm, 20 atmospheres and 15 atmospheres.

  The deuteration method of the present invention may be carried out in a sealed state in the reaction system and pressurized by adding hydrogen gas. The reaction system may further contain, for example, an inert gas such as nitrogen gas or argon gas.

  When the deuteration method of the present invention is performed in a sealed state, it may be performed using, for example, a pressurized container or the like that is usually used for performing a pressure reaction, and the range of the reaction pressure and the amount of hydrogen gas used is limited. What is necessary is just to use suitably the pressurized container of the capacity | capacitance which satisfy | fills from a commercially available thing.

  In the deuteration method of the present invention, the dehydrogenation reaction of the substrate can be promoted by appropriately removing the hydrogen gas generated in the reaction system by the dehydrogenation reaction.

  The operation for removing the hydrogen gas in the reaction system includes, for example, a method of reducing the reaction temperature to below the boiling point of the deuterated solvent to be used and removing the hydrogen gas in a state close to normal pressure in the reaction system, The method of gradually removing hydrogen gas may be mentioned, but considering safety, the method of lowering the reaction temperature and removing hydrogen gas in a state close to normal pressure is preferable.

  Further, for example, a hydrogen gas absorbent (for example, an adsorption catalyst such as a metal catalyst, zeolite, alumina, activated carbon, etc.), and a reducing substance that can react with it and remove hydrogen gas [for example, aldehyde, ketone, olefin (for example, malee) Acid, dimethyl maleate, α-methylstyrene, transstilbene, tetralin, indene, etc.)] may be added to the reaction system in advance to remove the hydrogen gas.

  In the present invention, the removal of hydrogen gas is preferably carried out in several steps from 30 minutes after the start of the reaction to after the end of the reaction.

  The lower limit of the reaction temperature of the deuteration method of the present invention is usually 10 ° C, preferably 20 ° C, 40 ° C, 50 ° C in order, and the upper limit is usually 200 ° C, more preferably 180 ° C, 100 ° C, 60 ° C. ° C.

  The reaction time of the deuteration method of the present invention is usually 30 minutes to 120 hours, preferably 1 to 100 hours, more preferably 10 to 80 hours, and further preferably 12 to 60 hours.

  The deuteration method of the present invention will be described using an example in which deuterated water is used as a deuterated solvent and a palladium catalyst and / or a platinum catalyst is used as a catalyst.

That is, for example, 1 mol of a compound (substrate) represented by the general formula [1], [2], [22] or [26] according to the present invention and 0.01 to 200% by weight of a palladium catalyst (based on the substrate) Palladium metal is 0.0005-20% by weight with respect to the substrate), platinum catalyst (platinum metal is 0.0005-20% by weight with respect to the substrate), or mixed catalyst (1: 1) consisting of palladium catalyst and platinum catalyst (with palladium metal The total amount of platinum metal is 0.0005 to 20% by weight based on the substrate) to a deuterated solvent (1 to 20000 equivalents, preferably 10 to 700 equivalents to the mixed catalyst), and the reaction system is After sealing and replacing the inside of the system with hydrogen gas, the reaction is allowed to stir in an oil bath at about 20 to 200 ° C. for about 30 minutes to 100 hours. After completion of the reaction, the reaction solution is filtered to remove the catalyst, and after purification, ¹ H-NMR, ² H-NMR, Mass spectrum, etc. are measured to perform structural analysis.

If it is difficult to isolate the product from the reaction solution, the filtrate may be directly measured by ¹ H-NMR using an appropriate internal standard substance, and the structure of the product may be analyzed. In order to isolate the product from the reaction solution when the product is hardly soluble in the deuterated solvent, for example, the product is extracted from the reaction solution with an organic solvent or the like in which the product is dissolved, and further filtered. Purification may be performed according to a known purification method such as removing the catalyst.

  According to the deuteration method of the present invention, the substrate dehydrogenation reaction and deuteration reaction can be carried out in one pot, and the obtained deuterated product is obtained by directly deuterating the substrate dehydrogenated product. It can be produced at a higher deuteration rate than the case.

  The deuterated product obtained by the deuteration method of the present invention is useful as a raw material for optical fibers, organic EL materials and the like.

  The present invention will be described more specifically with reference to the following examples. However, the present invention is not limited to these examples.

  In the following examples, palladium carbon having a palladium metal content of 10% by weight and platinum carbon having a platinum metal content of 5% by weight were used.

  Moreover, the deuteration rate in the following Examples and Comparative Examples is obtained as follows.

That is, after completion of the predetermined reaction, the reaction solution was extracted with ether, the catalyst was filtered, the filtrate was concentrated under reduced pressure, ¹ H-NMR, ² H-NMR and Mass spectra were measured to perform structural analysis, and the reaction The deuteration rate of hydrogen atoms contained in the substrate was determined. In each table, each deuteration rate indicates the deuteration rate of the hydrogen atom at the position of the number appended to the structural formula of each reaction substrate.

Example 1.
After suspending 500 mg of 1,2,3,4-tetrahydronaphthalene, 50 mg of 10% palladium carbon and 100 mg of 5% platinum carbon in 17 ml of heavy water (D ₂ O) and purging the sealed reaction system with hydrogen, The reaction was allowed to proceed for about 24 hours at ° C. After completion of the reaction, the reaction solution was extracted with ethyl acetate, the catalyst was filtered off, the filtrate was concentrated under reduced pressure, and the structure was analyzed by measuring ¹ H-NMR and ² H-NMR. Deuterated naphthalene (target product) and deuterated 1,2,3,4-tetrahydronaphthalene (by-product) were separated by atmospheric distillation. Table 1 also shows the deuteration rate of the obtained target product and by-products. In Table 1, each deuteration rate indicates the deuteration rate of the hydrogen atom at the position of the number appended to the structural formula of the reaction substrate.

Example 2
A deuteration reaction was carried out in the same manner as in Example 1 except that the reaction time was 48 hours and the hydrogen gas in the system was removed several times. In the hydrogen gas removal operation, about 12 hours after the start of the reaction, the reaction temperature is lowered to about 80 ° C., the pressure in the reaction system is lowered to a state close to normal pressure, and then the sealed reaction vessel is opened. Was done. This operation was repeated three more times (every 12 hours). The results are also shown in Table 1.

Example 3
A deuteration reaction was carried out in the same manner as in Example 1 except that 100 mg of 10% palladium carbon and 200 mg of 5% platinum carbon were used as the catalyst, the reaction time was 48 hours, and the hydrogen gas in the system was removed several times. . In the hydrogen gas removal operation, about 12 hours after the start of the reaction, the reaction temperature is lowered to about 80 ° C., the pressure in the reaction system is lowered to a state close to normal pressure, and then the sealed reaction vessel is opened. Was done. This operation was repeated three more times (every 12 hours). The results are also shown in Table 1.

Example 4
A deuteration reaction was performed in the same manner as in Example 1 except that 50 mg of 10% palladium carbon was used as a catalyst, the reaction time was 48 hours, and hydrogen gas in the system was removed several times. In the hydrogen gas removal operation, about 12 hours after the start of the reaction, the reaction temperature is lowered to about 80 ° C., the pressure in the reaction system is lowered to a state close to normal pressure, and then the sealed reaction vessel is opened. Was done. This operation was repeated three more times (every 12 hours). The results are also shown in Table 1.

Comparative Example 1
A deuteration reaction was carried out in the same manner as in Example 1 except that naphthalene was used as a reaction substrate and 50 mg of 10% palladium carbon was used as a catalyst. The results are also shown in Table 1.

Comparative Example 2
A deuteration reaction was performed in the same manner as in Example 1 except that naphthalene was used as a reaction substrate and 100 mg of 5% platinum carbon was used as a catalyst. The results are also shown in Table 1.

Comparative Example 3
A deuteration reaction was performed in the same manner as in Example 1 except that naphthalene was used as a reaction substrate. The results are also shown in Table 1.

  As is clear from the results in Table 1, when deuteration was performed using naphthalene as the substrate, naphthalene could hardly be deuterated (results of Comparative Examples 1 to 3). On the other hand, when dehydrogenation and deuteration are performed in one pot using 1,2,3,4-tetrahydronaphthalene as a substrate, the desired deuterated naphthalene can be obtained with a high deuteration rate. It turned out that (result of Examples 1-4). Moreover, it turned out that the direction of using the mixed catalyst of a palladium catalyst and a platinum catalyst as a catalyst improves the yield of a target object rather than the case where a palladium single catalyst is used (Examples 1-3 and Example 4). Results). Furthermore, it was found that the production of the target product was promoted when the hydrogen gas was removed in the deuteration reaction (results of Examples 1 and 2-3).

Example 5 FIG.
1,2,3,4, -Tetrahydrocarbazole 500 mg, 10% palladium carbon (10 wt%) 50 mg and 5% platinum carbon (20 wt%) 100 mg were suspended in 17 ml of heavy water (D ₂ O), and the sealed reaction system was After purging with hydrogen, the reaction was carried out in an oil bath at 180 ° C. for about 24 hours. After completion of the reaction, the reaction solution was extracted with ethyl acetate, the catalyst was filtered off, the filtrate was concentrated under reduced pressure, and the structure was analyzed by measuring ¹ H-NMR and ² H-NMR. By recrystallization from acetone, almost pure deuterated carbazole (target product) could be obtained. Table 2 also shows the deuteration rate of the obtained target product and by-products. In Table 2, each deuteration rate indicates the deuteration rate of the hydrogen atom at the position of the number appended to the structural formula of the reaction substrate.

Example 6
A deuteration reaction was carried out in the same manner as in Example 5 except that the reaction time was 48 hours. The results are also shown in Table 2.

Example 7
A deuteration reaction was performed in the same manner as in Example 5 except that hydrogen in the system was removed several times. In the hydrogen gas removal operation, about 12 hours after the start of the reaction, the reaction temperature is lowered to about 80 ° C., the pressure in the reaction system is lowered to a state close to normal pressure, and then the sealed reaction vessel is opened. Was done. This operation was repeated three more times (every 12 hours). The results are also shown in Table 2.

Comparative Example 4
A deuteration reaction was performed in the same manner as in Example 3 except that carbazole was used as a reaction substrate. The results are also shown in Table 2.

Comparative Example 5
The deuteration reaction was performed in the same manner as in Example 3 except that the reaction time was 48 hours and carbazole was used as the reaction substrate. The results are also shown in Table 2.

Comparative Example 6
Deuteration reaction was carried out in the same manner as in Example 5 except that carbazole was used as a reaction substrate, 50 mg of 10% palladium carbon was used as a catalyst, the reaction time was 24 hours, and hydrogen gas in the system was removed several times. It was. The results are also shown in Table 2.

  As is clear from the results in Table 2, when carbazole was used as a substrate for deuteration, carbazole could hardly be deuterated (results of Comparative Examples 4 to 6). On the other hand, the method of the present invention in which dehydrogenation and deuteration are performed in one pot using 1,2,3,4-tetrahydrocarbazole as a substrate provides the desired deuterated carbazole at a high deuteration rate. (Results of Examples 5 to 7).

  As is clear from the results of Example 5 and Example 6, when the reaction time is longer, the target deuterated carbazole can be obtained at a higher deuteration rate and the generation of by-products can be suppressed. did it.

  As is clear from the results of Example 5 and Example 6, it was also found that when the hydrogen gas in the reaction system was removed several times during the deuteration reaction of the present invention, the production of the target product was further promoted. It was.

Claims (9)

In the coexistence of a catalyst selected from a palladium catalyst, a platinum catalyst, a nickel catalyst, a cobalt catalyst, an iridium catalyst, a rhodium catalyst and a ruthenium catalyst, the general formula [1]

{Wherein, two R ¹ s each independently represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, _{X 1} and _{X 4} are each independently a nitrogen atom or the formula [14]

(Wherein R ³ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms) . } Or a compound represented by the general formula [2]

{Wherein, four R ⁴ s each independently represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, _{X 2} represents an oxygen atom or a general formula [15]

(Wherein, ^{R 6} represents. A hydrogen atom or an alkyl group having 1 to 3 carbon atoms) a group represented by. } Is reacted with a deuterated solvent, represented by the general formula [6]

{Wherein the two R ^1a each independently, deuterated which may be an alkyl group having 1 to 3 carbon atoms, represents a heavy hydrogen atom or a hydrogen atom, four R ^2a are independently And X _1a and X _4a each independently represent a nitrogen atom or a general formula [18]

(Wherein, R ^3a is deuterated optionally alkyl group having 1 to 3 carbon atoms, a heavy hydrogen atom or a hydrogen atom.) Represents a group represented by. However, and that at least one deuterium atom of hydrogen atom the compounds possess. } Or a general formula [7]

{Wherein, four in the R ^4a each independently represent a deuterated which may be an alkyl group having 1 to 3 carbon atoms, represents a heavy hydrogen atom or a hydrogen atom, four R ^5a are independently And represents a deuterium atom or a hydrogen atom, and X _2a represents an oxygen atom or a general formula [19]

(Wherein, R ^6a is deuterated optionally alkyl group having 1 to 3 carbon atoms, a heavy hydrogen atom or a hydrogen atom.) Represents a group represented by. However, at least one of the hydrogen atoms possessed by the present compound is a deuterium atom. Method for producing a deuterated compound represented by}. 2 R ¹ , R ³ 4 R ⁴ And R ⁶ Are both hydrogen atoms, and two R ^1a , R ^3a 4 R ^4a And R ^6a The deuteration method according to claim 1, wherein each independently represents a deuterium atom or a hydrogen atom. The deuteration method according to claim 1 or 2 , which is carried out under sealed conditions. The deuteration method according to any one of claims 1 to 3 , wherein the catalyst is a mixed catalyst of a palladium catalyst and a platinum catalyst. The deuteration method according to any one of claims 1 to 4 , wherein the palladium catalyst is palladium carbon and the platinum catalyst is platinum carbon. The deuteration method according to any one of claims 1 to 5 , which is carried out in the presence of hydrogen gas. A deuterated solvent is heavy water (D 2 _O), deuteration method according to any of claims 1-6. A general formula [1] a compound represented by 1,2,3,4-tetrahydronaphthalene, the compound represented by the obtained formula [6] is a deuterated naphthalene, claim 1-7 The deuteration method described in 1. A compound 1,2,3,4-tetrahydrocarbazole of the formula [2], a compound represented by the obtained formula [7] is a deuterated carbazole, claim 1-7 The deuteration method described in 1.