JPH06256249A - Production of azulenequinone compound - Google Patents

Abstract

PURPOSE:To obtain in high purity a compound useful for medicines, electrophotographic sensitizers, liquid crystal elements, organic conductors, etc., by reaction between an azulene compound and bromine in acetic acid to form a bromoazulenequinone which is then made to react with a nucleophilic reagent. CONSTITUTION:An azulene compound of formula I (R is 1-4C alkyl; n is 0-6, etc.) is first made to react with bromine in acetic acid at 0 deg.C to room temperature to form a bromoazulenequinone compound of formula II or III (m is 1 or 2), which is then made to react with a nucleophilic reagent (e.g. sodium methylate) in an alcoholic solvent at 10-80 deg.C to easily obtain the azulenequinone compound of formula IV or V (Nu is 1-4C alkoxy, amino, 1-6C alkyl, anilino, etc.) at low cost. The compound of the formula II is e.g. 3-bromo-1,7- azulenequinone, while the compound of the formula IV is e.g. 3-(p-toluidino)-1,7- azulenequinone.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing azulene quinones, more specifically, pharmaceuticals, electrophotographic photoreceptors,
The present invention relates to a novel method for producing azulene quinones useful for liquid crystal elements, organic conductors and the like.

[0002]

BACKGROUND OF THE INVENTION Azulene is known as a component of the essential oils of Artemisia or Chamomile, which have long been regarded as a medicinal product by the private sector, but in recent years, azulene quinones are especially anti-inflammatory agents. In addition to its use as a drug for treating hyperlipidemia, anticancer drug, etc., it is also expected to be used for electrophotographic photoreceptors, liquid crystal elements, organic conductors, etc., and is attracting attention from various fields.

As a method for synthesizing azulene quinones, which are increasing in usefulness, the Uda-Takase method (Chemi
story Letters, 197 (1980); ib
id. , 1661 (1981); ibid. , 1303
(1982)), Nozomu and Matsubara method (Chemistry)
Letters, 627 (1984); ibid. , 6
31 (1984), Scott method (J. Am. Chem.
Soc. , 106 , 4852 (1984), ibi.
d. , 106 , 4857 (1984)) and the like.

However, each of the above-mentioned methods has problems such as multistep reaction steps, low reaction selectivity and low yield.

Therefore, it has been desired to develop a method for solving these problems and producing a high-purity azulenequinone easily and inexpensively.

[0006]

Means for Solving the Problems The inventors of the present invention have made extensive studies in view of such circumstances, and as a result, readily available azulene or alkyl-substituted azulene is reacted with bromine in acetic acid to give bromoazulenequinone. The inventors have found that the compounds can be obtained, and further that azulenequinones can be obtained by reacting the bromoazulenequinones with a nucleophile, and thus completed the present invention.

That is, the present invention provides the following general formula (5):

[0008]

[Chemical 4]

(In the formula, R represents an alkyl group having 1 to 4 carbon atoms, and n represents a number of 0 to 6, provided that at least one of the 1- and 3-positions, 5 and 7-positions is hydrogen. Azulene represented by the following general formula (1) or (2), characterized by reacting with bromine in acetic acid.

[0010]

[Chemical 5]

(In the formula, m represents an integer of 1 to 2, and R, n
Is as defined above. The present invention provides a method for producing bromoazulene quinones represented by the formula (1).

The present invention further comprises reacting the bromoazulene quinones (1) or (2) with a nucleophile, represented by the following general formula (3) or (4).

[0013]

[Chemical 6]

(In the formula, Nu is an alkoxy group having 1 to 4 carbon atoms or an amino group, an alkyl group having 1 to 6 carbon atoms, an alkylthio group or an alkyleneamino group, an anilino group,
The present invention provides a method for producing an azulenequinone represented by a toluidino group, a mercapto group or an active methylene group, and R, n and m have the same meanings as described above.

Specific examples of R in the above general formulas (1) to (5) include methyl, ethyl, propyl, isopropyl,
Examples thereof include alkyl groups such as butyl, isobutyl and t-butyl.

Specific examples of the group Nu produced by the nucleophile in the above general formulas (3) and (4) include alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy and t-butoxy, Alkylamino groups such as methylamino, dimethylamino, ethylamino, diethylamino, propylamino, anilino, toludino, pyrrolidino, piperidino, morpholino, aromatic amino groups and alkyleneamino groups, methylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio, etc. Alkylthio groups, active methylene radicals such as malonnitrile, diethyl malonate, and ethyl acetoacetate.

The bromoazulene quinones (1) or (2) according to the present invention are produced by adding 2 to 6 equivalents, preferably 3 to 4.5 equivalents of bromine in acetic acid or acetic acid to 1 equivalent of the azulene (5). The reaction is carried out in a mixed solvent of water and water at 0 ° C. to room temperature for 5 minutes to 5 hours. The acetic acid content in the acetic acid / water mixed solvent is preferably 10% or more.

The reaction liquid thus obtained is then preferably treated with water. The water treatment is carried out by pouring the obtained reaction mixture into water and filtering the precipitated crystals, or by pouring the reaction mixture into a suitable organic solvent such as benzene for extraction.

The crystals or extracts obtained as described above are preferably purified by known means such as fractional recrystallization and column chromatography. The desired bromoazulene quinones (1) or (2) are obtained by these purification means.
Can be obtained in a high yield of around 50%.

The azulenequinones (3) or (4) of the present invention can be produced by reacting the bromoazulenequinones (1) or (2) with a nucleophile.

The nucleophile used in the present invention is one in which the reagent participating in the reaction has a tendency to give an electron to the other party in an ionic reaction. Specifically, sodium alcoholate such as sodium methylate, toluidine, etc. And amines, thiols such as butylthiol, and active methylene compounds such as malonnitrile.

The production of azulenequinones (3) or (4) by reacting the bromoazulene quinones (1) or (2) with a nucleophile is carried out in an amount of 1 equivalent or more per 1 equivalent of the bromoazulene quinones. It is carried out by reacting a nucleophile in an alcoholic solvent at 10 to 80 ° C. for 5 minutes to 24 hours.

Examples of the alcohol used include lower alcohols such as methanol and ethanol.

The obtained reaction product is preferably purified by a known means such as fractional recrystallization or column chromatography. By these purification means, the target azulenequinones (3) or (4) can be obtained in a yield of 80% or more.

[0025]

According to the method of the present invention, high-purity azulenequinones useful for medicines, electrophotographic photoreceptors, liquid crystal devices, organic conductors, etc. can be obtained easily and inexpensively.

[0026]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited thereto.

Example 1 3-Brom-1,7-azulenequinone (1a) and 3-
Production of bromo-1,5-azulenequinone (2a) (75
% Acetic acid) Azulene 200 mg (1.56 mmo) in a 50 ml eggplant flask.
l) was taken and dissolved by heating in 40 ml of acetic acid. 14m to this
l of distilled water was added and cooled to room temperature. To this solution, 840 mg (5.25 mmol) of bromine dissolved in 4 ml of acetic acid was added at room temperature, and the mixture was stirred for 20 minutes. Then, add this reaction solution to 8
It was poured into 00 ml of distilled water and further stirred at room temperature for 1 hour.
After the formed precipitate was filtered by suction, the filtrate was extracted with benzene (twice), washed with water (twice), and dried over magnesium sulfate. After removing the solvent, the product (1
184 mg (0.78 mmol) of the mixture of a) and (2a)
Obtained (yield 50%). This mixture was subjected to silica gel column chromatography (Merck Art. 9385, K).
iselgel 60, benzene: methanol = 50:
Separation and purification according to 1) gave (1a) and (2a) in a ratio of 1: 3.

[0028]

[Chemical 7]

Pale yellow needles; mp 142 ° C decomposition IR (KBr): 3100,2920,1710,1642,1584,1522,1430,1380,12
80,1268,1172,1138,1040,997,925,850,812cm ^{-1 1} H NMR (270MHz, CDCl ₃ ) δ: 6.81 (1H, s, H-2), 6.91 (1H, ddd, J = 12.2,2.7,0.8Hz , H-
6), 7.05 (1H, ddd, J = 8.2,0.8,0.5Hz, H-4), 7.17 (1H, dd, J = 1
2.2,8.2Hz, H-5), 7.24 (1H, dd, J = 2.7,0.5Hz, H-8) .MS (70eV): m / z 238 (M ⁺ , 11%), 236 (M ⁺ , 11%), 210 (15%), 2
08 (15%), 129 (100%), 101 (50%).

[0030]

[Chemical 8]

Pale yellow needles; mp 135 ° C decomposition IR (KBr): 3080,3040,3000,1700,1640,1623,1585,1564,15
32,1430,1290,1233,1178,1013,905,872,849,816,624,59
5 cm ^{-1 1} H NMR (270 MHz, CDCl ₃ ) δ: 6.87 (1H, d, J = 0.7Hz, H-2), 7.02 (1H, ddd, J = 12.1,2.4,
1.5Hz, H-6), 7.11 (1H, dt, J = 2.4,0.7Hz, H-4), 7.17 (1H, dd,
J = 12.1,8.0Hz, H-7), 7.31 (1H, ddd, J = 8.0,1.5,0.7Hz, H-
8). ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ: 127.522 (d), 133.585 (d), 13
4.460 (d), 134.460 (s), 136.471 (d), 144.045 (d), 144.272
(s), 152.705 (s), 186.276 (s), 189.665 (s) .MS (70eV): m / z 238 (M ⁺ , 10%), 236 (M ⁺ , 10%), 210 (15%) , 2
. 08 (15%), 129 (100%) measurements:. C, 50.56; H, 2.23; N, 0.00% _{Calculated: (C 10 H 5 Br 2} ): C, 50.67; H, 2.13; N, 0.00%.

Example 2 3-Brom-1,7-azulenequinone (1a) and 3-
Production of Brom-1,5-azulenequinone (2a) (67
% Acetic acid) Azulene 200 mg (1.56 mmo) in a 50 ml eggplant flask.
l) was taken and dissolved by heating in 40 ml of acetic acid. 20m to this
l of distilled water was added and cooled to room temperature. To this solution, 840 mg (5.25 mmol) of bromine dissolved in 4 ml of acetic acid was added at room temperature, and the mixture was stirred for 20 minutes. Then, this reaction solution was treated in the same manner as in Example 1 to obtain 160 mg (0.68 mmol) of the desired mixture of (1a) and (2a) (yield 43.
%).

Example 3 3-Brom-1,7-azulenequinone (1a) and 3-
Production of Brom-1,5-azulenequinone (2a) (85
% Reaction in acetic acid) Azulene 200 mg (1.56 mmo) in a 50 ml eggplant flask.
l) was taken and dissolved by heating in 40 ml of acetic acid. 8 ml to this
Of distilled water was added, and the mixture was cooled to room temperature. To this solution, 840 mg (5.25 mmol) of bromine dissolved in 4 ml of acetic acid was added at room temperature, and the mixture was stirred for 20 minutes. Then, this reaction solution was treated in the same manner as in Example 1 to obtain 144 mg (0.61 mmol) of the desired mixture of (1a) and (2a) (yield 39%).

Example 4 3-Brom-1,7-azulenequinone (1a) and 3-
Production of bromo-1,5-azulenequinone (2a) (98
% Reaction in acetic acid) Azulene 200 mg (1.56 mmo) in a 50 ml eggplant flask.
l) was taken, dissolved by heating in 40 ml of acetic acid, and cooled to room temperature. 800 mg of bromine dissolved in 4 ml of acetic acid
(5.00 mmol) was added at room temperature and stirred for 10 minutes. Thereafter, this reaction solution was treated in the same manner as in Example 1 to obtain 140 mg (0.59 mm) of the desired mixture of (1a) and (2a).
ol) was obtained (yield 38%).

Example 5 3,5-dibromo-1,7-azulenequinone (1b) and 3,7-dibromo-1,5-azulenequinone (2b)
200 mg of azulene (1.56 mmo in a 50 ml eggplant flask)
l) was taken, dissolved by heating in 40 ml of acetic acid, and cooled to room temperature. 1.1 g of bromine dissolved in 4 ml of acetic acid
(6.88 mmol) was added at room temperature and stirred for 10 minutes.
Then, the reaction solution was poured into 800 ml of distilled water and further stirred at room temperature for 1 hour. The formed precipitate was filtered by suction, the filtrate was extracted with benzene (twice), washed with water (twice), and dried over magnesium sulfate. After removing the solvent, vacuum drying was performed to obtain 150 mg of (1a), (2a) and (1b),
The respective mixtures of (2b) were obtained. This mixture was subjected to silica gel column chromatography (Merck Art.
9385, Kiselgel 60, benzene: methanol = 50: 1) to separate and purify to obtain the desired mixture of (1b) and (2b) [yield: 15%, the ratio of (1b) and (2b): 1: 3].

[0036]

[Chemical 9]

Light yellow needle crystals; mp 153 ° C decomposition IR (KBr): 3100,2920,2850,1705,1636,1590,1524,1401,13
68,1296,1253,1239,1192,1037,910,902,853,811,739,61
2 cm ^{-1 1} H NMR (270 MHz, CDCl ₃ ) δ: 6.88 (1H, s, H-2), 7.19 (1H, dd, J = 2.6,0.7Hz, H-4), 7.25
(1H, dd, J = 2.3,0.7Hz, H-8), 7.42 (1H, dd, J = 2.6,2.3Hz, H-
6) .MS (70eV): m / z 318 (M ⁺ , 3%), 316 (M ⁺ , 5%), 314 (M ⁺ , 3%),
290 (20%), 288 (40%), 286 (21%), 209 (96%), 207 (100
Measured: M ⁺ , 313.8540,315.8586, and 317.8555 (1: 2: 1). Calculated: (C ₁₀ H ₄ OBr): M, 313.8578,315.8559,317.8539.

[0038]

[Chemical 10]

Pale yellow needle crystals; mp 138 ° C decomposition IR (KBr): 3090,2920,2850,1706,1635,1584,1530,1400,13
70,1300,1282,1250,1218,1190,1050,908,880,850,757,6
34,615 cm ^{-1 1} H NMR (270MHz, CDCl ₃ ) δ: 6.89 (1H, d, J = 0.6Hz, H-2), 7.06 (1H, ddd, J = 2.1,0.8,0.
6Hz, H-4), 7.48 (1H, dd, J = 2.3,0.8Hz, H-8), 7.50 (1H, dd, J =
2.3,2.1Hz, H-6) .MS (70eV): m / z 318 (M ⁺ , 5%), 316 (M ⁺ , 10%), 314 (M ⁺ , 6)
%), 290 (17%), 288 (33%), 286 (18%), 209 (100%), 207 (1
Measured value: M ⁺ , 313.8540,315.8586,317.8555 (1: 2: 1). Calculated value: (C ₁₀ H ₄ OBr): M, 313.8578,315.8559,317.8539.

Example 6 3- (p-toluidino) -1,7-azulenequinone (3
Preparation of a) 140 mg (0.59 mmol) of 3-bromo-1,7-azulenequinone (1a) was placed in a 20 ml eggplant flask and added to 20 ml.
Was dissolved in methanol by heating and cooled to room temperature. 90 mg of p-toluidine dissolved in 2 ml of methanol was added to this solution.
(0.84 mmol) was added at room temperature and stirred. After 1 hour of reaction, the formed precipitate was filtered and the mother liquor was subjected to silica gel column chromatography (benzene: methanol = 50:
Separation and purification according to 1) yielded (3a) (yield 95
%).

[0041]

[Chemical 11]

Yellow prismatic crystals; mp 282 ° C decomposition IR (KBr): 3240,2920,1668,1638,1590,1542,1508,1408,11
95,817,615 cm ^{-1 1} H NMR (270MHz, DMSO-d ₆ ) δ: 2.23 (3H, s, CH ₃ ), 5.79 (1H, s, H-2), 6.85 (1H, dd, J = 11.
9,2.8Hz, H-6), 6.88 (1H, d, J = 2.8Hz, H-8), 7.28 (4H, m, H-
2 ', 3', 5 ', 6'), 7.35 (1H, dd, J = 11.9,8.4Hz, H-5), 7.61 (1H,
d, J = 8.4Hz, H-4), 10.15 (1H, br, NH) .MS (70eV): m / z 263 (M ⁺ , 57%), 235 (94%), 234 (57%), 207
(100%), 206 (92%). Actual value: C, 77.49; H, 5.26; N, 4.99% .Calculated value: (C ₁₇ H ₁₃ NO ₂ ): C, 77.55; H, 4.98; N, 5.32 %.

Example 7 3- (p-toluidino) -1,5-azulenequinone (4
Production of a) In the same manner as in Example 6, 3-brom-1,5-azulenequinone (1a) was reacted with p-toluidine to obtain (4a) (yield 94%).

[0044]

[Chemical 12]

Yellow prismatic crystals; mp 290 ° C decomposition IR (KBr): 3240,3020,1664,1640,1592,1580,1545,1510,13
95,1238,1190,911,803cm ^{-1 1} H NMR (270MHz, DMSO-d ₆ ) δ: 2.22 (3H, s, CH ₃ ), 5.82 (1H, s, H-2), 6.88 (1H, ddd, J = 11.
6,2.6,0.8Hz, H-6), 7.17 (1H, dd, J = 7.8,0.8Hz, H-8), 7.28
(4H, m, H-2 ', 3', 5 ', 6'), 7.33 (1H, dd, J = 11.6,7.8Hz, H-7),
7.57 (1H, d, J = 2.6Hz, H-4), 9.81 (1H, br, NH) .MS (70eV): m / z 263 (M ⁺ , 87%), 246 (37%), 234 ( 100%), 207
(51%), 206 (77%). Actual value: C, 77.46; H, 5.29; N, 5.08% .Calculated value: (C ₁₇ H ₁₃ NO ₂ ): C, 77.55; H, 4.98; N, 5.32 %.

Example 8 3-Butylamino-1,7-azulenequinone (3b) and 3-butylamino-1,5-azulenequinone (4b)
Preparation of 110 mg (0.46 mmol) of a mixture of (1a) and (1b) (mixing ratio; 1: 3) was weighed in a 20 ml flask and 10
It was dissolved by heating in a mixed solution of methanol (5 ml) and chloroform (5 ml) and cooled to room temperature. To this solution, 70 mg (0.96 mmol) of n-butylamine dissolved in 1 ml of methanol was added at room temperature and stirred. After 30 minutes of reaction, the solvent was removed,
The residue was separated and purified by silica gel column chromatography (benzene: methanol = 50: 1), and
b) (23 mg, yield 86%) and (4b) (65 mg, yield 82%) were obtained.

[0047]

[Chemical 13]

Yellow needles; mp 178-180 ° C IR (KBr): 3240,2950,2920,2850,1665,1641,1610-1550,14
60,1376,1250,1212,1110,1035,995,905,855,795,645cm
^{-1 1} H NMR (270MHz, CDCl ₃ ) δ: 0.99 (3H, t, J = 7.3Hz, CH ₃ ), 1.46 (2H, m, CH ₂ ), 1.72 (2H,
m, CH ₂ ), 3.38 (2H, m, NCH ₂ ), 5.56 (1H, s, H-2), 5.61 (1H, br, N
H), 6.72 (1H, dd, J = 8.1,0.8Hz, H-4), 6.89 (1H, ddd, J = 12.2,
2.7,0.8Hz, H-6), 7.05 (1H, dd, J = 12.2,8.1Hz, H-5), 7.26 (1
H, d, J = 2.7Hz, H-8) .MS (70eV): m / z 229 (M ⁺ , 43%), 186 (15%), 159 (100%), 158
(25%), 145 (30%), 130 (48%). Actual value: M ⁺ , 229.1091. Calculated value: (C ₁₄ H ₁₅ NO ₂ ): M, 229.1102.

[0049]

[Chemical 14]

Yellow prism-like crystals; mp 202-204 ° C IR (KBr): 3250,2950,2925,2860,1665,1640,1600-1500,14
60,1438,1370,1235,1190,1105,915,855,792,628cm ^{-1 1} H NMR (270MHz, CDCl ₃ ) δ: 0.98 (3H, t, J = 7.3Hz, CH ₃ ), 1.46 (2H, m, CH ₂ ), 1.78 (2H,
m, CH ₂ ), 3.44 (2H, m, NCH ₂ ), 5.59 (1H, s, H-2), 5.82 (1H, br, N
H), 6.92 (1H, dt, J = 11.1,2.3Hz, H-6), 7.25 (1H, dd, J = 11.1,
8.3Hz, H-7), 7.29 (1H, dd, J = 8.3,2.3Hz, H-8), 7.47 (1H, d, J
= 2.3Hz, H-4). ¹³ C NMR (67.8MHz, CDCl ₃ ) δ: 13.736 (q, CH ₃ ), 20.159 (t, CH
₂ ), 30.522 (t, CH ₂ ), 45.393 (t, CH ₂ ), 101.830 (d), 124.568
(d), 127.341 (d), 137.428 (d), 141.142 (d), 141.369 (s), 14
3.315 (s), 164.966 (s), 187.768 (s), 188.043 (s) .MS (70eV): m / z 229 (M ⁺ , 45%), 186 (23%), 159 (100%), 158
(31%), 130 (58%). Actual value: M ⁺ , 229.1091. Calculated value: (C ₁₄ H ₁₅ NO ₂ ): M, 229.1102.

Example 9 3-Methoxy-1,7-azulenequinone (3c) and 3
Preparation of -methoxy-1,5-azulenequinone (4c) In a 50 ml round-bottomed flask, 150 mg (0.63 mmol) of the mixture (1: 3) of (1a) and (2a) was weighed and added to 20 ml.
Was dissolved in dry methanol by heating and cooled to room temperature. To this solution, 70 mg (1.30 mmol) of sodium methylate dissolved in 1 ml of methanol was added at room temperature and stirred. After 20 minutes from the reaction, the raw material disappeared, so saturated saline was added thereto, and the mixture was extracted with benzene (twice), washed with water (twice), and dried over magnesium sulfate. The extraction liquid removes the solvent,
The residue was separated and purified by silica gel column chromatography (benzene: methanol = 50: 1), and
c) (20 mg, 67% yield) and (4c) (55 mg, 62% yield) were obtained.

[0052]

[Chemical 15]

Pale yellow needles; mp 207 ° C IR (KBr): 3080,3020,2940,1705,1640,1600-1530,1440,13
50,1250,1230,1185,1095,1039,945,850,832,820,764,73
0,645cm ^{-1 1} H NMR (270MHz, CDCl ₃ ) δ: 4.07 (3H, s, OCH ₃ ), 5.72 (1H, s, H-2), 6.89 (1H, ddd, J = 1
1.9,2.5,1.3Hz, H-6), 7.00 (1H, ddd, J = 8.0,1.3,0.7Hz, H-
4), 7.09 (1H, dd, J = 11.9,8.0Hz, H-5), 7.27 (1H, dd, J = 2.5,
0.7 Hz, H-8). ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ: 59.308 (q), 104.328 (d), 122.
784 (d), 132.498 (d), 135.028 (d), 138.774 (s), 139.131
(s), 141.288 (d), 141.466 (s), 187.850 (s), 190.087 (s) .MS (70eV): m / z 188 (M ⁺ )

[0054]

[Chemical 16]

Pale yellow needles; mp 215 ° C IR (KBr): 3060,2950,2920,2850,1700,1640,1610-1540,14
32,1350,1255,1235,1188,1085,1035,940,912,850,820,8
00,715cm ^{-1 1} H NMR (270MHz, CDCl ₃ ) δ: 4.06 (3H, s, OCH ₃ ), 5.73 (1H, d, J = 0.8Hz, H-2), 6.95 (1H,
ddd, J = 12.1,2.6,1.1Hz, H-6), 7.06 (1H, dt, J = 2.6,0.8Hz, H
-4), 7.14 (1H, dd, J = 12.1,7.8Hz, H-7), 7.29 (1H, ddd, J = 7.
8, 1.1, 0.8 Hz, H-8). ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ: 59.292 (q), 105.447 (d), 106.
355 (s), 126.627 (d), 129.206 (d), 135.125 (d), 137.623
(s), 141.510 (s), 143.202 (s), 187.005 (s), 189.681 (s) .MS (70eV): m / z 188 (M ⁺ , 31%), 159 (28%), 102 (100 %).

Example 10 Preparation of 3-butylthio-1,7-azulenequinone (3d) and 3-butylthio-1,5-azulenequinone (4d) A mixture of (1a) and (2a) (ratio) in a 50 ml round-bottomed flask. Weigh 90 mg (0.38 mmol) of 1: 3), and
It was dissolved by heating in 5 ml of dry methanol and cooled to room temperature. 200 mg (2.22) of n-butylthiol was added to this solution.
mmol) was added at room temperature and stirred. After 3 hours of reaction, saturated saline was added to this, and benzene extraction (twice) was performed.
It was washed twice with N-NaOH, washed with water (twice), and dried over magnesium sulfate. The solvent was removed from the extract, and the residue was separated and purified by silica gel column chromatography (benzene: methanol = 50: 1) (3d) (16
mg, yield 69%) and (4d) (42 mg, yield 60%)
Got

[0057]

[Chemical 17]

Yellow crystal; mp 68-70 ° C. ¹ H NMR (270 MHz, CDCl ₃ ) δ: 1.00 (3 H, t, J = 7.3 Hz, CH ₃ ), 1.52 (2 H, m, CH ₂ ), 1.80 (2 H ,
m, CH ₂ ), 3.08 (2H, t, J = 7.3Hz SCH ₂ ), 6.33 (1H, s, H-2), 6.89
(1H, dd, J = 8.0,0.8Hz, H-4), 6.90 (1H, ddd, J = 12.4,2.8,0.8
Hz, H-6), 7.10 (1H, dd, J = 12.4,8.0Hz, H-5), 7.28 (1H, d, J =
2.8Hz, H-8) .MS (70eV): m / z 246 (M ⁺ , 27%), 218 (7%), 162 (100%).

[0059]

[Chemical 18]

Yellow crystal; mp 135-138 ° C. ¹ H NMR (270 MHz, CDCl ₃ ) δ: 0.99 (3H, t, J = 7.3Hz, CH ₃ ), 1.52 (2H, m, CH ₂ ), 1.80 (2H ,
m, CH ₂ ), 3.07 (2H, t, J = 7.3Hz SCH ₂ ), 6.36 (1H, s, H-2), 6.96
(1H, dd, J = 11.8,2.4,1.2Hz, H-6), 6.98 (1H, dd, J = 2.4Hz, H
-4), 7.15 (1H, dd, J = 11.8,7.9Hz, H-7), 7.26 (1H, dd, J = 7.9,
1.2 Hz, H-8). ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ: 13.514 (q), 22.058 (t), 29.97
9 (t), 32.564 (t), 96.153 (s), 1025.307 (d), 126.481 (d), 13
0.496 (d), 135.025 (d), 137.060 (s), 143.075 (d), 145.348
(s), 186.842 (s), 189.079 (s) .MS (70eV): m / z 246 (M ⁺ , 24%), 218 (10%), 162 (100%).

Example 11 Of 3-bromo-4,6,8-trimethyl-1,7-azulenequinone (3e) and 3-bromo-4,6,8-trimethyl-1,5-azulenequinone (4e) Manufacturing 4,6,8-Trimethylazulene 200mg in 50ml eggplant flask
(1.18 mmol) was taken and dissolved by heating in 40 ml of acetic acid. To this, 14 ml of distilled water was added and cooled to room temperature.
To this solution, 600 mg of bromine dissolved in 4 ml of acetic acid (3.7
(5 mmol) was added at room temperature and stirred for 20 minutes. afterwards,
The reaction solution was poured into 800 ml of distilled water and the mixture was further mixed at room temperature for 1 hour.
Stir for hours. The formed precipitate was filtered by suction, the filtrate was extracted with benzene (twice), washed with water (twice), and dried over magnesium sulfate. After removing the solvent, the residue was dried in vacuum to give 174 mg (0.6
2 mmol) was obtained (yield 53%).

[0062]

[Chemical 19]

(3e) pale yellow needle crystals; mp 128 ° C. decomposition,
(4e) Pale yellow needle crystals; mp 160 ℃ decomposition ¹ H NMR (270MHz, CDC
l ₃ ) (mixture) δ: 2.25 (3H, d, J = 1.5Hz, CH ₃ ), 2.58 (3H, s, CH ₃ ), 2.69 (3H,
s, CH ₃ ), 6.73 (1H, s, H-2), 6.90 (1H, q, J = 1.5Hz, H-5) .MS (70eV): m / z 280 (M ⁺ , 11%), 278 (M ⁺ , 11%), 252 (11%), 2
50 (11%), 171 (100%), 128 (31%).

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location C07C 221/00 225/20 7457-4H 319/14 323/22 7419-4H

Claims (2)

[Claims] 1. The following general formula (5): (In the formula, R represents an alkyl group having 1 to 4 carbon atoms, and n is 0
Indicates a number of ~ 6. However, at least one of the 1- and 3-positions, 5 and 7-positions is a hydrogen atom. ) The azulene represented by the formula (1) or (2) below is reacted with bromine in acetic acid. (In the formula, m represents an integer of 1 to 2, R and n have the same meanings as described above), and a method for producing bromoazulene quinones. 2. A bromoazulene quinone (1) or (2) according to claim 1, which is reacted with a nucleophile, represented by the following general formula (3) or (4): (In the formula, Nu represents an alkoxy group or amino group having 1 to 4 carbon atoms, an alkyl group having 1 to 6 carbon atoms, an alkylthio group or an alkyleneamino group, an anilino group, a toluidino group, a mercapto group or an active methylene group, and R , N,
and m has the same meaning as defined above).