JP5357559B2 - Compound having dimethoxynaphthalene skeleton and process for producing the same - Google Patents
Compound having dimethoxynaphthalene skeleton and process for producing the same Download PDFInfo
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- 0 COc1ccc(ccc(OC)c2C(c3ccc(*)cc3)=O)c2c1 Chemical compound COc1ccc(ccc(OC)c2C(c3ccc(*)cc3)=O)c2c1 0.000 description 7
- YIPPWOPVVKOGJL-UHFFFAOYSA-N COc(cc1)c(C(c(cc2)ccc2C(O)=O)=O)c2c1ccc(OC)c2C(c(cc1)ccc1F)=O Chemical compound COc(cc1)c(C(c(cc2)ccc2C(O)=O)=O)c2c1ccc(OC)c2C(c(cc1)ccc1F)=O YIPPWOPVVKOGJL-UHFFFAOYSA-N 0.000 description 1
- PPKHAIRFQKFMLE-UHFFFAOYSA-N COc(cc1)cc2c1ccc(OC)c2 Chemical compound COc(cc1)cc2c1ccc(OC)c2 PPKHAIRFQKFMLE-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
本発明は、新規なジメトキシナフタレン骨格を有する化合物及びその製造方法に関する。 The present invention relates to a compound having a novel dimethoxynaphthalene skeleton and a method for producing the same.
本発明者らは、ジメトキシナフタレン骨格を有する化合物についての研究を進めており、既に非特許文献１にて下記一般式(A)で示される１，８−ビス（４−クロロベンゾイル）−２，７−ジメトキシナフタレンを、非特許文献２にて下記一般式(B)で示される１，８−ジベンゾイル−２，７−ジメトキシナフタレンを提案した。 The present inventors are advancing research on a compound having a dimethoxynaphthalene skeleton, and 1,8-bis (4-chlorobenzoyl) -2 represented by the following general formula (A) in Non-Patent Document 1 has already been obtained. Non-patent document 2 proposed 1,8-dibenzoyl-2,7-dimethoxynaphthalene represented by the following general formula (B) in Non-Patent Document 2.
しかしながら、上記化合物は何れも対称型のものであって、反応性に欠ける等の問題がある。本発明者らは、更に研究を進め、非対称型（２つのベンゾイルに異なる置換基を有するもの）の２，７−ジメトキシナフタレン化合物の合成を図るものである。 However, the above compounds are all symmetrical and have problems such as lack of reactivity. The present inventors will further research and aim to synthesize an asymmetric type (having different substituents in two benzoyl groups) of 2,7-dimethoxynaphthalene compounds.
本発明者らは、新たに非対称型（２つのベンゾイルに異なる置換基を有するもの）の２，７−ジメトキシナフタレン化合物を効率良く製造する方法を見出し、本発明を完成するに至った。 The present inventors have found a new method for efficiently producing an asymmetric type (having different substituents on two benzoyl groups) of 2,7-dimethoxynaphthalene compounds, and have completed the present invention.
即ち本発明は、下記一般式（Ｉ）で示されるジメトキシナフタレン骨格を有する化合物である。 That is, the present invention is a compound having a dimethoxynaphthalene skeleton represented by the following general formula (I).
（式中、Ｒ1及びＲ2は、ＯＨ、ハロゲン、ＮＯ2、ＮＨ2、ＣＯＯＲ3、ＯＣＯＣＨ3及びＣＨ2Ｒ4から選ばれる基であり、Ｒ1とＲ2が同一であることはない。また、Ｒ3はＨまたはＣＨ3であり、Ｒ4はハロゲンまたはＯＨである。また、Ｍｅはメチル基を示す。ハロゲンとしてはフッ素、臭素等が挙げられる。） (In the formula, R 1 and R 2 are groups selected from OH, halogen, NO 2 , NH 2 , COOR 3 , OCOCH 3 and CH 2 R 4 , and R 1 and R 2 are not the same. R 3 is H or CH 3 , R 4 is halogen or OH, Me represents a methyl group, and examples of halogen include fluorine and bromine.
本発明の化合物の具体例としては、以下のものが挙げられる。 Specific examples of the compound of the present invention include the following.
以下、本発明の化合物の合成例を示す。 Hereafter, the synthesis example of the compound of this invention is shown.
本発明の化合物の製造方法において、出発原料は、下記一般式（II） In the process for producing the compound of the present invention, the starting material is represented by the following general formula (II)
（式中、Ｍｅはメチル基を示す。）
で示される２，７−ジメトキシナフタレンである。
(In the formula, Me represents a methyl group.)
Is 2,7-dimethoxynaphthalene.
本発明では、第一段階目のアロイル化として、上記２，７−ジメトキシナフタレンと下記一般式（III） In the present invention, as the first stage aroylation, the above 2,7-dimethoxynaphthalene and the following general formula (III)
（式中、Ｒ1は、ＯＨ、ハロゲン、ＮＯ2、ＮＨ2、ＣＯＯＲ3、ＯＣＯＣＨ3及びＣＨ2Ｒ4から選ばれる基であり、Ｒ3はＨまたはＣＨ3であり、Ｒ4はハロゲンまたはＯＨである。）
で示される化合物とをＡｌＣｌ3、ＳｂＣｌ5、ＦｅＣｌ3、ＴｅＣｌ2、ＳｎＣｌ4、ＴｉＣｌ4、ＴｅＣｌ4、ＢｉＣｌ3及びＺｎＣｌ2より選ばれる強ルイス酸（ａ）の存在下に反応させる。
Wherein R 1 is a group selected from OH, halogen, NO 2 , NH 2 , COOR 3 , OCOCH 3 and CH 2 R 4 , R 3 is H or CH 3 and R 4 is halogen or OH.)
Is reacted in the presence of a strong Lewis acid (a) selected from AlCl 3 , SbCl 5 , FeCl 3 , TeCl 2 , SnCl 4 , TiCl 4 , TeCl 4 , BiCl 3 and ZnCl 2 .
第一段階目のアロイル化反応において、強ルイス酸（ａ）の存在下に反応させることにより下記一般式（IV） In the aroylation reaction in the first stage, the reaction is carried out in the presence of a strong Lewis acid (a) to give the following general formula (IV)
で示される化合物（１−モノ置換体）が得られる。 Is obtained (1-mono-substituted product).
次いで、上記一般式（IV）で示される化合物（１−モノ置換体）と下記一般式（Ｖ） Subsequently, the compound represented by the above general formula (IV) (1-mono-substituted product) and the following general formula (V)
（式中、Ｒ2は、ＯＨ、ハロゲン、ＮＯ2、ＮＨ2、ＣＯＯＲ3、ＯＣＯＣＨ3及びＣＨ2Ｒ4から選ばれる基であり、Ｒ3はＨまたはＣＨ3であり、Ｒ4はハロゲンまたはＯＨである。）
で示される化合物とを上記強ルイス酸（ａ）より相対的に弱いルイス酸（ｂ）の存在下に反応（第二段階目のアロイル化反応）させることにより、選択的に目的とする一般式（Ｉ）で示されるジメトキシナフタレン骨格を有する化合物（１，８−ジ置換体）が得られる。
(Wherein R 2 is a group selected from OH, halogen, NO 2 , NH 2 , COOR 3 , OCOCH 3 and CH 2 R 4 , R 3 is H or CH 3 , and R 4 is halogen or OH.)
Is reacted in the presence of a Lewis acid (b) that is relatively weaker than the strong Lewis acid (a) (second-stage aroylation reaction) to selectively produce a general formula of interest. A compound (1,8-disubstituted product) having a dimethoxynaphthalene skeleton represented by (I) is obtained.
この第二段階目のアロイル化反応では、第一段階目のアロイル化反応で用いた上記強ルイス酸（ａ）より相対的に弱いルイス酸（ｂ）が使用される。 In the second stage aroylation reaction, a Lewis acid (b) that is relatively weaker than the strong Lewis acid (a) used in the first stage aroylation reaction is used.
このようなルイス酸（ｂ）としては、ＴｉＣｌ4や強ルイス酸（ａ）として例示したものの中から選択して使用することもできるが、ＴｉＣｌ4が好ましい。 Such Lewis acid (b) can be selected from TiCl 4 and those exemplified as strong Lewis acid (a), but TiCl 4 is preferred.
尚、第二段階目のアロイル化反応では、下記一般式（VI） In the second stage aroylation reaction, the following general formula (VI)
（式中、Ｒ2は、ＯＨ、ハロゲン、ＮＯ2、ＮＨ2、ＣＯＯＲ3、ＯＣＯＣＨ3及びＣＨ2Ｒ4から選ばれる基であり、Ｒ3はＨまたはＣＨ3であり、Ｒ4はハロゲンまたはＯＨである。）
で示される化合物とを五酸化二リン−メタンスルホン酸等のリン酸系の酸性縮合剤の存在下で直接縮合反応させることもできる。
(Wherein R 2 is a group selected from OH, halogen, NO 2 , NH 2 , COOR 3 , OCOCH 3 and CH 2 R 4 , R 3 is H or CH 3 , and R 4 is halogen or OH.)
It is also possible to carry out a direct condensation reaction with a compound represented by the above in the presence of a phosphoric acid-based acidic condensing agent such as diphosphorus pentoxide-methanesulfonic acid.
本発明の製造方法では、後記実施例で示すように、適当な化合物を反応させることにより、所望とする置換基を有する化合物に変換可能である。 In the production method of the present invention, as shown in Examples described later, it can be converted into a compound having a desired substituent by reacting an appropriate compound.
実施例１
1-(4-ブロモメチルベンゾイル)-8-(4-フルオロベンゾイル)-2,7-ジメトキシナフタレンの合成（経路1）
Example 1
Synthesis of 1- (4-bromomethylbenzoyl) -8- (4-fluorobenzoyl) -2,7-dimethoxynaphthalene (Route 1)
減圧加熱乾燥および窒素置換した10 mLナスフラスコに, 4-ブロモメチル安息香酸クロリド(0.22 mmol, 51,4 mg), CH2Cl2 (1.0 mL) を加え, 氷浴でかき混ぜた。そこへAlCl3 (0.44 mmol, 53.3 mg) を加え数分かき混ぜた。さらに, 2,7-ジメトキシナフタレン (0.20 mmol, 37.6 mg)を加え, 6時間かき混ぜた。反応終了後, 反応溶液を氷水にあけクロロホルムで抽出し(10 mL×3), 2M水酸化ナトリウム水溶液(10 mL×3),飽和食塩水 (10 mL×3) で洗浄した。有機層を無水硫酸マグネシウムで乾燥させ, エバポレーターで溶媒留去した。得られた粗生成物は,クロロホルム/ヘキサン混合溶媒より再結晶(白色, 針状)して精製した(収率 86%)。その後, 1H-NMRスペクトルにより構造確認およびX線結晶構造解析を行い、目的化合物が得られたことを確認した。 4-Bromomethylbenzoic acid chloride (0.22 mmol, 51,4 mg) and CH 2 Cl 2 (1.0 mL) were added to a 10 mL eggplant flask heated under reduced pressure and purged with nitrogen, and the mixture was stirred in an ice bath. AlCl 3 (0.44 mmol, 53.3 mg) was added thereto and stirred for several minutes. Furthermore, 2,7-dimethoxynaphthalene (0.20 mmol, 37.6 mg) was added and stirred for 6 hours. After completion of the reaction, the reaction solution was poured into ice water, extracted with chloroform (10 mL × 3), washed with 2M aqueous sodium hydroxide solution (10 mL × 3) and saturated brine (10 mL × 3). The organic layer was dried over anhydrous magnesium sulfate and evaporated using an evaporator. The obtained crude product was purified by recrystallization (white, needle-like) from a chloroform / hexane mixed solvent (yield 86%). Thereafter, structure confirmation and X-ray crystal structure analysis were performed by 1 H-NMR spectrum, and it was confirmed that the target compound was obtained.
次いで、三方コックを付した10 mL一口ナスフラスコを減圧加熱乾燥後窒素置換し, 4-フルオロ安息香酸クロリド(0.44 mmol, 69.8 mg), CH2Cl2 (0.25 mL) を加え室温でかき混ぜた。そこへTiCl4 (1.8 mmol, 0.3414 g) を入れ, 数分かき混ぜた。さらに, 1-(4-ブロモメチルベンゾイル)-2,7-ジメトキシナフタレン(0.20 mmol, 77.1 mg)のCH2Cl2 (0.5 mL) 溶液を加え, 3時間かき混ぜた。反応終了後, 反応溶液を氷水にあけてクロロホルムで抽出(10 mL×3), 有機層を2M水酸化ナトリウム水溶液 (10 mL×3),飽和食塩水 (10 mL×3) で洗浄後, 無水硫酸マグネシウムで乾燥させた。エバポレーターで溶媒を留去した後, 得られた粗生成物はEtOHより再結晶(収率 65%, 黄色, 針状)またはEt2O/ヘキサン混合溶媒を用いて精製した(収率 83%)。その後, 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定およびX線結晶構造解析を行った。結果を以下に示す。 Next, a 10 mL one-necked eggplant flask equipped with a three-way cock was dried by heating under reduced pressure, purged with nitrogen, 4-fluorobenzoic acid chloride (0.44 mmol, 69.8 mg), CH 2 Cl 2 (0.25 mL) was added, and the mixture was stirred at room temperature. TiCl 4 (1.8 mmol, 0.3414 g) was put there and stirred for several minutes. Further, a solution of 1- (4-bromomethylbenzoyl) -2,7-dimethoxynaphthalene (0.20 mmol, 77.1 mg) in CH 2 Cl 2 (0.5 mL) was added and stirred for 3 hours. After completion of the reaction, the reaction solution was poured into ice water and extracted with chloroform (10 mL × 3) .The organic layer was washed with 2M aqueous sodium hydroxide solution (10 mL × 3) and saturated brine (10 mL × 3), then anhydrous. Dried over magnesium sulfate. After distilling off the solvent with an evaporator, the obtained crude product was purified by recrystallization from EtOH (yield 65%, yellow, needle-like) or using Et 2 O / hexane mixed solvent (yield 83%). . After that, the structure was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Furthermore, melting point measurement and X-ray crystal structure analysis were performed. The results are shown below.
1H-NMR (300 MHz, CDCl3) : 3.70 (6H, s), 4.50 (2H, s), 7.00 (2H, t, J= 8.4, 8.4 Hz), 7.21 (2H, d, J= 9.0 Hz), 7.34 (2H, d, J= 7.2 Hz), 7.61〜7.72 (4H, m), 7.96 (2H, d, J=9.0 Hz) ppm
13C-NMR (300 MHz, CDCl3) : 32.676, 56.355, 56.388, 111.104, 111.162, 115.002, 115.291, 120.887, 120.977, 125.453, 128.758, 129.483, 129.755, 131.584, 131.700, 132.268, 138.433, 141.994, 156.243, 156.383, 167.196, 195.465, 196.256 ppm
IR (KBr) : 1664 (C=O), 1608, 1510 (Ar), 1268 (Ar-O), 1044 (O-Me) cm-1
C27H20BrFO4 ; Anal. Calcd for C, 63.92; H, 3.97
Found C, 63.72; H, 4.16
m.p.=151.9〜152.4℃
実施例２
1-(4-ブロモメチルベンゾイル)-8-(4-フルオロベンゾイル)-2,7-ジメトキシナフタレンの合成（経路２）
1 H-NMR (300 MHz, CDCl 3 ): 3.70 (6H, s), 4.50 (2H, s), 7.00 (2H, t, J = 8.4, 8.4 Hz), 7.21 (2H, d, J = 9.0 Hz ), 7.34 (2H, d, J = 7.2 Hz), 7.61-7.72 (4H, m), 7.96 (2H, d, J = 9.0 Hz) ppm
13 C-NMR (300 MHz, CDCl 3 ): 32.676, 56.355, 56.388, 111.104, 111.162, 115.002, 115.291, 120.887, 120.977, 125.453, 128.758, 129.483, 129.755, 131.584, 131.700, 132.268, 138.433, 141.994, 156.243, 156.383, 167.196, 195.465, 196.256 ppm
IR (KBr): 1664 (C = O), 1608, 1510 (Ar), 1268 (Ar-O), 1044 (O-Me) cm -1
C 27 H 20 BrFO 4 ; Anal. Calcd for C, 63.92; H, 3.97
Found C, 63.72; H, 4.16
mp = 151.9-152.4 ° C
Example 2
Synthesis of 1- (4-bromomethylbenzoyl) -8- (4-fluorobenzoyl) -2,7-dimethoxynaphthalene (Route 2)
三方コックを付した10 mL一口ナスフラスコを減圧加熱乾燥後窒素置換し, 4-フルオロ安息香酸クロリド(0.44 mmol, 69.8 mg), CH2Cl2 (1.0 mL) を加え, 氷浴でかき混ぜた。そこへAlCl3 (0.48 mmol, 64.0 mg) を入れ, 数分かき混ぜた。さらに, 2,7-ジメトキシナフタレン(0.40 mmol, 75.3 mg)を加え, 3時間かき混ぜた。反応溶液を氷水にあけてクロロホルムで抽出(20 mL×3), 有機層を2M 水酸化ナトリウム水溶液(20 mL×3),飽和食塩水 (20 mL×3) で洗浄後, 無水硫酸マグネシウムで乾燥させた。エバポレーターで溶媒を留去した後, Et2Oより再結晶(無色, 針状)またはエタノール/ヘキサンを用いて精製した(収率 79%)。得られた生成物は, 1H-NMRスペクトルで構造確認およびX線結晶構造解析を行い、目的化合物が得られたことを確認した。 A 10 mL round neck flask equipped with a three-way cock was heated under reduced pressure and purged with nitrogen. 4-Fluorobenzoic acid chloride (0.44 mmol, 69.8 mg) and CH 2 Cl 2 (1.0 mL) were added, and the mixture was stirred in an ice bath. AlCl 3 (0.48 mmol, 64.0 mg) was added thereto and stirred for several minutes. Furthermore, 2,7-dimethoxynaphthalene (0.40 mmol, 75.3 mg) was added and stirred for 3 hours. The reaction solution was poured into ice water and extracted with chloroform (20 mL × 3) .The organic layer was washed with 2M aqueous sodium hydroxide solution (20 mL × 3) and saturated brine (20 mL × 3), and then dried over anhydrous magnesium sulfate. I let you. After evaporating the solvent with an evaporator, it was recrystallized from Et 2 O (colorless, needle-like) or purified using ethanol / hexane (yield 79%). The obtained product was subjected to structure confirmation and X-ray crystal structure analysis by 1 H-NMR spectrum to confirm that the target compound was obtained.
次いで、三方コックを付した10 mL一口ナスフラスコを減圧加熱乾燥後窒素置換し, 4-ブロモメチル安息香酸(0.22 mmol, 47.3 mg),五酸化二リン−メタンスルホン酸 (0.44 mL) を入れ, 60oCで完全に溶解するまでかき混ぜた。その後, 1-(4-フルオロベンゾイル)-2,7-ジメトキシナフタレン(0.20 mmol, 62.1 mg)を入れ1時間かき混ぜた。反応溶液を氷水にあけてクロロホルムで抽出(10 mL×3), 有機層を2M水酸化ナトリウム水溶液(10 mL×3),飽和食塩水 (10 mL×3)で洗浄後, 無水硫酸マグネシウムで乾燥させた。エバポレーターで溶媒を留去し, 粗生成物を得た(収率 89%)。その後, シリカゲルカラムクロマトグラフィー(クロロホルム)より精製し(収率 26%), 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定およびX線結晶構造解析を行った。結果は実施例１と同様であった。 Next, a 10 mL one-necked eggplant flask equipped with a three-way cock was dried by heating under reduced pressure and purged with nitrogen, and 4-bromomethylbenzoic acid (0.22 mmol, 47.3 mg), diphosphorus pentoxide-methanesulfonic acid (0.44 mL) were added, and o Stir with C until completely dissolved. Then, 1- (4-fluorobenzoyl) -2,7-dimethoxynaphthalene (0.20 mmol, 62.1 mg) was added and stirred for 1 hour. The reaction solution was poured into ice water and extracted with chloroform (10 mL × 3) .The organic layer was washed with 2M aqueous sodium hydroxide solution (10 mL × 3) and saturated brine (10 mL × 3), then dried over anhydrous magnesium sulfate. I let you. The solvent was distilled off with an evaporator to obtain a crude product (yield 89%). After purification by silica gel column chromatography (chloroform) (yield 26%), the structure was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Furthermore, melting point measurement and X-ray crystal structure analysis were performed. The result was the same as in Example 1.
実施例３
1-(4-フルオロベンゾイル)-8-(4-ヒドロキシメチルベンゾイル)-2,7-ジメトキシナフタレンの合成
Example 3
Synthesis of 1- (4-fluorobenzoyl) -8- (4-hydroxymethylbenzoyl) -2,7-dimethoxynaphthalene
ジムロー冷却管を付した30 mL一口ナスフラスコに,実施例１で得た1-(4-ブロモメチルベンゾイル)-8-(4-フルオロベンゾイル)-2,7-ジメトキシナフタレン(0.20 mmol, 0.1015 g), 1,4-ジオキサン(4.0 mL)を加えて溶液にした。さらに1.3M炭酸カルシウム水溶液(3.2 mL) を加え, 12時間加熱還流させた。反応終了後, 反応溶液に2M塩酸水溶液をかき混ぜながら徐々に加えて均一な溶液としてから, 水(15.0 mL)を加えた。析出した固体を吸引ろ集した(収率 91%)。得られた生成物は, 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定を行った。結果を以下に示す。 1- (4-Bromomethylbenzoyl) -8- (4-fluorobenzoyl) -2,7-dimethoxynaphthalene (0.20 mmol, 0.1015 g) obtained in Example 1 was added to a 30 mL one-necked eggplant flask equipped with a Dimro condenser. ), 1,4-dioxane (4.0 mL) was added to give a solution. Furthermore, 1.3M calcium carbonate aqueous solution (3.2 mL) was added, and the mixture was heated to reflux for 12 hours. After completion of the reaction, 2M aqueous hydrochloric acid solution was gradually added to the reaction solution with stirring to obtain a homogeneous solution, and then water (15.0 mL) was added. The precipitated solid was collected by suction filtration (yield 91%). The structure of the obtained product was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Further, the melting point was measured. The results are shown below.
1H-NMR (300 MHz, CDCl3) : 3.68 (3H, s), 3.69 (3H, s), 4.74 (2H, s), 7.00 (2H, t, J= 8.7, 8.7 Hz), 7.20 (1H, d, J= 9.0 Hz), 7.21 (1H, d, J= 9.0 Hz), 7.34 (2H, d, J= 8.4 Hz), 7.67〜7.73 (4H, m), 7.95 (2H, d, J=9.0 Hz) ppm
13C-NMR (300 MHz, CDCl3) : 56.339, 56.367, 64.853, 111.058, 111.077, 111.191, 114.995, 120.888, 121.202, 125.483, 126.189, 129.364, 129.783, 131.595, 131.690, 132.138, 132.253, 132.291, 137.869, 145.706, 156.185, 156.309, 195.458, 196.640 ppm
IR (KBr) : 3442 (OH), 1660 (C=O), 1608, 1596, 1509 (Ar), 1267, 1236 (Ar-O), 1044 (O-Me) cm-1
MS (FAB) : C27H22FO5 ; Exact Mass, 444.1373
[m/z + H+], 445.1484, +3.2 mmu
m.p.= 156.9〜158.8℃
実施例４
1-(4-カルボキシベンゾイル)-8-(4-フルオロベンゾイル)-2,7-ジメトキシナフタレンの合成
1 H-NMR (300 MHz, CDCl 3 ): 3.68 (3H, s), 3.69 (3H, s), 4.74 (2H, s), 7.00 (2H, t, J = 8.7, 8.7 Hz), 7.20 (1H , d, J = 9.0 Hz), 7.21 (1H, d, J = 9.0 Hz), 7.34 (2H, d, J = 8.4 Hz), 7.67-7.73 (4H, m), 7.95 (2H, d, J = 9.0 Hz) ppm
13 C-NMR (300 MHz, CDCl 3 ): 56.339, 56.367, 64.853, 111.058, 111.077, 111.191, 114.995, 120.888, 121.202, 125.483, 126.189, 129.364, 129.783, 131.595, 131.690, 132.138, 132.253, 132.291, 137.869, 145.706, 156.185, 156.309, 195.458, 196.640 ppm
IR (KBr): 3442 (OH), 1660 (C = O), 1608, 1596, 1509 (Ar), 1267, 1236 (Ar-O), 1044 (O-Me) cm -1
MS (FAB): C 27 H 22 FO 5 ; Exact Mass, 444.1373
[m / z + H + ], 445.1484, +3.2 mmu
mp = 156.9-158.8 ° C
Example 4
Synthesis of 1- (4-carboxybenzoyl) -8- (4-fluorobenzoyl) -2,7-dimethoxynaphthalene
ジムロー冷却管を付した30 mL二口ナスフラスコに10 mL滴下ロートを付し,実施例３で得た 1-(4-フルオロベンゾイル)-8-(4-ヒドロキシメチルベンゾイル)-2,7-ジメトキシナフタレン(0.078 mmol, 34.7 mg), アセトン(3.0 mL)を加え加熱還流させた。さらに,過マンガン酸カリウム水溶液 (0.470 mmol, 74.0 mg/1.60 mL) を徐々に滴下し, さらに6時間加熱還流した。反応終了後, 反応溶液をろ過し, ろ液に2M硫酸水溶液を酸性になるまで加え, さらに水(20.0 mL)を加えた。析出した固体を吸引ろ集した(収率 89%)。得られた生成物は, 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定を行った。結果を以下に示す。 1- (4-Fluorobenzoyl) -8- (4-hydroxymethylbenzoyl) -2,7- obtained in Example 3 was attached to a 30 mL two-necked eggplant flask equipped with a Dimro condenser. Dimethoxynaphthalene (0.078 mmol, 34.7 mg) and acetone (3.0 mL) were added and heated to reflux. Furthermore, potassium permanganate aqueous solution (0.470 mmol, 74.0 mg / 1.60 mL) was gradually added dropwise, and the mixture was further heated under reflux for 6 hours. After completion of the reaction, the reaction solution was filtered, and 2M aqueous sulfuric acid solution was added to the filtrate until acidic, and water (20.0 mL) was further added. The precipitated solid was collected by suction filtration (yield 89%). The structure of the obtained product was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Further, the melting point was measured. The results are shown below.
1H-NMR (300 MHz, CDCl3) : 3.67 (3H, s), 3.71 (3H, s), 4.74 (2H, s), 7.04 (2H, t, J= 8.7, 8.7 Hz), 7.21 (1H, d, J= 9.0 Hz), 7.22 (1H, d, J= 9.0 Hz), 7.74 (2H, q, J= 5.7, 3.0, 5.7 Hz), 7.80 (2H, d, J= 8.7 Hz), 8.01 (2H, d, J= 9.0 Hz), 8.10 (2H, d, J=8.7 Hz) ppm
13C-NMR (300 MHz, CDCl3) : 56.291, 56.329, 77.200, 111.058, 111.134, 115.129, 115.348, 120.497, 120.688, 125.521, 128.868, 130.012, 131.690, 131.786, 132.367, 132.453, 132.634, 142.569, 156.404, 156.604, 170.649, 1969.058, 196.930 ppm
IR (KBr) : 3443 (OH), 1689, 1662 (C=O), 1611, 1595, 1509 (Ar), 1267 (Ar-O), 1233 (O-Me) cm-1
MS (FAB) : C27H19FO6 ; Exact Mass, 458.1166
[m/z + H+], 459.1255, +1.1 mmu
m.p.= 247.9〜249.7≡C
実施例５
1-(4-フルオロベンゾイル)-8-(4-メトキシカルボニルベンゾイル)-2,7-ジメトキシナフタレンの合成
1 H-NMR (300 MHz, CDCl 3 ): 3.67 (3H, s), 3.71 (3H, s), 4.74 (2H, s), 7.04 (2H, t, J = 8.7, 8.7 Hz), 7.21 (1H , d, J = 9.0 Hz), 7.22 (1H, d, J = 9.0 Hz), 7.74 (2H, q, J = 5.7, 3.0, 5.7 Hz), 7.80 (2H, d, J = 8.7 Hz), 8.01 (2H, d, J = 9.0 Hz), 8.10 (2H, d, J = 8.7 Hz) ppm
13 C-NMR (300 MHz, CDCl 3 ): 56.291, 56.329, 77.200, 111.058, 111.134, 115.129, 115.348, 120.497, 120.688, 125.521, 128.868, 130.012, 131.690, 131.786, 132.367, 132.453, 132.634, 142.569, 156.404, 156.604, 170.649, 1969.058, 196.930 ppm
IR (KBr): 3443 (OH), 1689, 1662 (C = O), 1611, 1595, 1509 (Ar), 1267 (Ar-O), 1233 (O-Me) cm -1
MS (FAB): C 27 H 19 FO 6 ; Exact Mass, 458.1166
[m / z + H + ], 459.1255, +1.1 mmu
mp = 247.9-249.7≡C
Example 5
Synthesis of 1- (4-fluorobenzoyl) -8- (4-methoxycarbonylbenzoyl) -2,7-dimethoxynaphthalene
ジムロー冷却管を付した10 mL一口ナスフラスコに,実施例４で得た 1-(4-カルボキシベンゾイル)-8-(4-フルオロベンゾイル)-2,7-ジメトキシナフタレン(0.20 mmol, 91.7 mg), MeOH (2.0 mL) 加えた。加熱還流後, 濃硫酸を一滴加えてさらに6時間加熱還流した。反応終了後, 反応溶液に水(5.0 mL)を加えクロロホルムで抽出し(10 mL×3),飽和食塩水 (10 mL×3) で洗浄した。有機層を無水硫酸マグネシウムで乾燥させ, エバポレーターで溶媒留去して生成物を得た(収率 84%)。得られた生成物は, 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定を行った。結果を以下に示す。 1- (4-Carboxybenzoyl) -8- (4-fluorobenzoyl) -2,7-dimethoxynaphthalene (0.20 mmol, 91.7 mg) obtained in Example 4 was placed in a 10 mL one-necked eggplant flask equipped with a Dimro condenser. , MeOH (2.0 mL) was added. After heating to reflux, a drop of concentrated sulfuric acid was added and the mixture was further heated to reflux for 6 hours. After completion of the reaction, water (5.0 mL) was added to the reaction solution, extracted with chloroform (10 mL × 3), and washed with saturated brine (10 mL × 3). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off with an evaporator to obtain the product (yield 84%). The structure of the obtained product was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Further, the melting point was measured. The results are shown below.
1H-NMR (300 MHz, CDCl3) : 3.66 (3H, s), 3.70 (3H, s), 3.93 (3H, s), 7.02 (2H, t, J= 8.7 Hz, 8.7 Hz), 7.20 (1H, d, J= 9.0 Hz), 7.21 (1H, d, J= 9.0 Hz), 7.70 (2H, q, J= 2.7, 6.0, 2.7 Hz), 7.76 (2H, d, J= 8.7 Hz), 8.01 (1H, d, J= 9.0 Hz), 8.02 (1H, d, J= 9.0 Hz), 8.03 (2H, d, J=8.7 Hz) ppm
13C-NMR (300 MHz, CDCl3) : 52.315, 56.281, 56.329, 77.210, 111.067, 111.124, 115.081, 115.300, 120.525, 120.620, 120.745, 125.521, 128.820, 128.859, 129.364, 132.396, 132.548, 133.302, 141.930, 156.366, 156.547, 166.596, 195.801, 196.630 ppm
IR (KBr) : 1723 (C=O), 1668 (C=O), 1606, 1596, 1510 (Ar), 1269 (Ar-O), 1231 (O-Me) cm-1
MS (FAB) : C28H21FO6 ; Exact Mass, 472.1322
[m/z + H+], 473.1365, -3.6 mmu
m.p.= 89.4〜92.1℃
実施例６
1-(4-カルボキシベンゾイル)-8-(4-ヒドロキシベンゾイル)-2,7-ジメトキシナフタレンの合成
1 H-NMR (300 MHz, CDCl 3 ): 3.66 (3H, s), 3.70 (3H, s), 3.93 (3H, s), 7.02 (2H, t, J = 8.7 Hz, 8.7 Hz), 7.20 ( 1H, d, J = 9.0 Hz), 7.21 (1H, d, J = 9.0 Hz), 7.70 (2H, q, J = 2.7, 6.0, 2.7 Hz), 7.76 (2H, d, J = 8.7 Hz), 8.01 (1H, d, J = 9.0 Hz), 8.02 (1H, d, J = 9.0 Hz), 8.03 (2H, d, J = 8.7 Hz) ppm
13 C-NMR (300 MHz, CDCl 3 ): 52.315, 56.281, 56.329, 77.210, 111.067, 111.124, 115.081, 115.300, 120.525, 120.620, 120.745, 125.521, 128.820, 128.859, 129.364, 132.396, 132.548, 133.302, 141.930, 156.366, 156.547, 166.596, 195.801, 196.630 ppm
IR (KBr): 1723 (C = O), 1668 (C = O), 1606, 1596, 1510 (Ar), 1269 (Ar-O), 1231 (O-Me) cm -1
MS (FAB): C 28 H 21 FO 6 ; Exact Mass, 472.1322
[m / z + H + ], 473.1365, -3.6 mmu
mp = 89.4〜92.1 ℃
Example 6
Synthesis of 1- (4-carboxybenzoyl) -8- (4-hydroxybenzoyl) -2,7-dimethoxynaphthalene
ジムロー冷却管を付した10 mL一口ナスフラスコに実施例４で得た1-(4-カルボキシベンゾイル)-8-(4-フルオロベンゾイル)-2,7-ジメトキシナフタレン(0.30 mmol, 0.1375 g)を入れ, DMSO (0.50 mL) に溶かした。18M水酸化ナトリウム水溶液 (3.0 mmol, 0.1200 g/0.60 mL)を加え, 120oCで12時間かき混ぜた。反応溶液に水(5.0 mL)を入れ反応溶液を均一にしてから, 2M塩酸水溶液 (20.0 mL) に滴下し, 析出した固体を吸引ろ集した(収率 97%)。得られた生成物はクロロホルムで洗浄し(収率 88%), 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定を行った。結果を以下に示す。 1- (4-Carboxybenzoyl) -8- (4-fluorobenzoyl) -2,7-dimethoxynaphthalene (0.30 mmol, 0.1375 g) obtained in Example 4 was placed in a 10 mL one-necked eggplant flask equipped with a Dimro condenser. And dissolved in DMSO (0.50 mL). 18M Aqueous sodium hydroxide solution (3.0 mmol, 0.1200 g / 0.60 mL) was added, and the mixture was stirred at 120 ° C. for 12 hr. Water (5.0 mL) was added to the reaction solution, and the reaction solution was homogenized. The solution was added dropwise to 2M aqueous hydrochloric acid (20.0 mL), and the precipitated solid was collected by suction filtration (yield 97%). The obtained product was washed with chloroform (yield 88%), and the structure was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Further, the melting point was measured. The results are shown below.
1H-NMR (300 MHz, (CD3)2SO2) : 3.52 (3H, s), 3.57 (3H, s), 6.62 (2H, br s), 7.27 (2H, br s), 7.38 (2H, d, J= 9.0 Hz), 7.50 (2H, d, J= 7.5 Hz) 7.86 (2H, d, J= 7.5 Hz), 8.09 (1H, d, J=9.0 Hz), 8.10 (1H, d, J=9.0 Hz), 10. (1H, s) ppm
13C-NMR δ (300 MHz, (CD3)2SO2) : 56.346, 56.370, 79.175, 111.631, 111.829, 114.787, 119.922, 120.664, 124.908, 128.526, 128.757, 129.062, 130.117, 131.345, 132.029, 132.515, 133.834, 141.268, 155.682, 155.954, 161.905, 166.850, 195.036 ppm
IR (KBr) : 3347 (OH), 1666 (C=O), 1606, 1574, 1510 (Ar), 1269 (Ar-O), 1233 (O-Me) cm-1
MS (FAB) : C27H21O7 ; Exact Mass, 456.1209
[m/z + H+], 457.1297, +1.0 mmu
m.p.= 256.6〜262.9℃
実施例７
1-(4-カルボキシベンゾイル)-8-(4-ヒドロキシベンゾイル)-2,7-ジメトキシナフタレンの合成
1 H-NMR (300 MHz, (CD 3 ) 2 SO 2 ): 3.52 (3H, s), 3.57 (3H, s), 6.62 (2H, br s), 7.27 (2H, br s), 7.38 (2H , d, J = 9.0 Hz), 7.50 (2H, d, J = 7.5 Hz) 7.86 (2H, d, J = 7.5 Hz), 8.09 (1H, d, J = 9.0 Hz), 8.10 (1H, d, J = 9.0 Hz), 10. (1H, s) ppm
13 C-NMR δ (300 MHz, (CD 3 ) 2 SO 2 ): 56.346, 56.370, 79.175, 111.631, 111.829, 114.787, 119.922, 120.664, 124.908, 128.526, 128.757, 129.062, 130.117, 131.345, 132.029, 132.515, 133.834, 141.268, 155.682, 155.954, 161.905, 166.850, 195.036 ppm
IR (KBr): 3347 (OH), 1666 (C = O), 1606, 1574, 1510 (Ar), 1269 (Ar-O), 1233 (O-Me) cm -1
MS (FAB): C 27 H 21 O 7 ; Exact Mass, 456.1209
[m / z + H + ], 457.1297, +1.0 mmu
mp = 256.6-262.9 ° C
Example 7
Synthesis of 1- (4-carboxybenzoyl) -8- (4-hydroxybenzoyl) -2,7-dimethoxynaphthalene
ジムロー冷却管を付した10 mL一口ナスフラスコに実施例５で得た1-(4-フルオロベンゾイル)-8-(4-メトキシカルボニルベンゾイル)-2,7-ジメトキシナフタレン(0.30 mmol, 0.1417 g)を入れ, DMSO (0.50 mL) に溶かした。18M水酸化ナトリウム水溶液(3.0 mmol, 0.1200 g/0.60 mL)を加え, 120℃で12時間かき混ぜた。反応溶液に水(5.0 mL)を入れ反応溶液を均一にしてから, 2M塩酸水溶液 (20.0 mL) に滴下し, 析出した固体を吸引ろ集した(収率 92%)。得られた生成物はクロロホルムで洗浄し(収率 78%), 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定を行った。結果は実施例６と同様であった。
実施例８
1-(4-ヒドロキシベンゾイル)-8-(4-メトキシカルボニルベンゾイル)-2,7-ジメトキシナフタレンの合成
1- (4-Fluorobenzoyl) -8- (4-methoxycarbonylbenzoyl) -2,7-dimethoxynaphthalene (0.30 mmol, 0.1417 g) obtained in Example 5 was added to a 10 mL one-necked eggplant flask equipped with a Dimro condenser. Was dissolved in DMSO (0.50 mL). 18M aqueous sodium hydroxide solution (3.0 mmol, 0.1200 g / 0.60 mL) was added, and the mixture was stirred at 120 ° C. for 12 hr. Water (5.0 mL) was added to the reaction solution, and the reaction solution was homogenized, and then added dropwise to 2M aqueous hydrochloric acid (20.0 mL), and the precipitated solid was collected by suction filtration (yield 92%). The obtained product was washed with chloroform (yield 78%), and the structure was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Further, the melting point was measured. The result was the same as in Example 6.
Example 8
Synthesis of 1- (4-hydroxybenzoyl) -8- (4-methoxycarbonylbenzoyl) -2,7-dimethoxynaphthalene
ジムロー冷却管を付した10 mL一口ナスフラスコに,実施例７で得た 1-(4-カルボキシベンゾイル)-8-(4-ヒドロキシベンゾイル)-2,7-ジメトキシナフタレン(0.20 mmol, 91.7 mg), MeOH (2.0 mL) 加えた。加熱還流後, 濃硫酸を一滴加えてさらに6時間加熱還流した。反応終了後, 反応溶液に水(5.0 mL)を加え, 析出した固体を吸引ろ集した(収率 90%)。得られた生成物はクロロホルムで洗浄し, 1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。さらに融点測定およびMeOHによる結晶化を行った。結果を以下に示す。 1- (4-Carboxybenzoyl) -8- (4-hydroxybenzoyl) -2,7-dimethoxynaphthalene (0.20 mmol, 91.7 mg) obtained in Example 7 was added to a 10 mL one-necked eggplant flask equipped with a Dimro condenser. , MeOH (2.0 mL) was added. After heating to reflux, a drop of concentrated sulfuric acid was added and the mixture was further heated to reflux for 6 hours. After completion of the reaction, water (5.0 mL) was added to the reaction solution, and the precipitated solid was collected by suction filtration (yield 90%). The obtained product was washed with chloroform, and the structure was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. Furthermore, melting point measurement and crystallization with MeOH were performed. The results are shown below.
1H-NMR (300 MHz, (CD3)2SO2) : 3.52 (3H, s), 3.70 (3H,s), 3.87 (3H,s), 6.80 (2H, d, J= 7.8 Hz), 7.32 (2H, d, J= 7.8 Hz), 7.44 (2H, d, J= 9.0 Hz), 7.58 (2H, d, J= 8.4 Hz), 7.93 (2H, d, J= 8.4 Hz), 8.15 (1H, d, J=9.0 Hz), 8.16 (1H, d, J=9.0 Hz) ppm
13C-NMR (300 MHz, (CD3)2SO2) : 39.723, 52.390, 56.206, 111.466, 111.655, 114.738, 119.469, 120.276, 122.790, 124.694, 128.576, 128.897, 129.054, 129.837, 132.111, 132.532, 141.325, 155.600, 155.897, 156.770, 161.789, 165.894, 195.143 ppm
IR (KBr): 3229 (OH), 1719, 1649 (C=O), 1607, 1583, 1510 (Ar), 1272 (O-Me) cm-1
MS (FAB) : C28H23O7 ; Exact Mass, 470.1366
[m/z + H+], 471.1488, +4.4 mmu
m.p.= 152.5〜153.5℃
実施例９
1-(4-アセトキシベンゾイル)-8-(4-カルボキシベンゾイル)-2,7-ジメトキシナフタレンの合成
1 H-NMR (300 MHz, (CD 3 ) 2 SO 2 ): 3.52 (3H, s), 3.70 (3H, s), 3.87 (3H, s), 6.80 (2H, d, J = 7.8 Hz), 7.32 (2H, d, J = 7.8 Hz), 7.44 (2H, d, J = 9.0 Hz), 7.58 (2H, d, J = 8.4 Hz), 7.93 (2H, d, J = 8.4 Hz), 8.15 ( 1H, d, J = 9.0 Hz), 8.16 (1H, d, J = 9.0 Hz) ppm
13 C-NMR (300 MHz, (CD 3 ) 2 SO 2 ): 39.723, 52.390, 56.206, 111.466, 111.655, 114.738, 119.469, 120.276, 122.790, 124.694, 128.576, 128.897, 129.054, 129.837, 132.111, 132.532, 141.325 , 155.600, 155.897, 156.770, 161.789, 165.894, 195.143 ppm
IR (KBr): 3229 (OH), 1719, 1649 (C = O), 1607, 1583, 1510 (Ar), 1272 (O-Me) cm -1
MS (FAB): C 28 H 23 O 7 ; Exact Mass, 470.1366
[m / z + H + ], 471.1488, +4.4 mmu
mp = 152.5-153.5 ℃
Example 9
Synthesis of 1- (4-acetoxybenzoyl) -8- (4-carboxybenzoyl) -2,7-dimethoxynaphthalene
（ここでAcはアセチル基を表す）
三方コックを付した10 mL一口ナスフラスコを減圧加熱乾燥後窒素置換し, 実施例７で得た1-(4-カルボキシベンゾイル)-8-(4-ヒドロキシベンゾイル)-2,7-ジメトキシナフタレン(0.20 mmol, 91.7 mg),無水酢酸(0.50 mL) を入れて, 室温で数分かき混ぜた。そこへ濃硫酸を一滴加え, さらに30分間かき混ぜた。反応溶液に2M水酸化ナトリウム水溶液で中和し, さらに水(5.0 mL)を加え, 析出した固体を吸引ろ集した(収率 96%)。得られた生成物は1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。結果を以下に示す。
1H-NMR (300 MHz, CDCl3) : 2.30 (3H, s), 3.68 (3H, s), 3.71 (3H, s), 7.10 (2H, t, J= 8.4 Hz), 7.21 (1H, d, J= 9.0 Hz), 7.23 (1H, d, J= 9.0 Hz), 7.72 (2H, d, J= 8.4 Hz), 7.79 (2H, d, J= 8.1 Hz), 7.97 (1H, d, J= 9.0 Hz), 7.98 (1H, d, J= 9.0 Hz) 8.09 (2H, d, J=8.1 Hz) ppm
(Ac here represents an acetyl group)
A 10 mL one-necked eggplant flask equipped with a three-way cock was heated under reduced pressure and then purged with nitrogen, and 1- (4-carboxybenzoyl) -8- (4-hydroxybenzoyl) -2,7-dimethoxynaphthalene obtained in Example 7 ( 0.20 mmol, 91.7 mg) and acetic anhydride (0.50 mL) were added, and the mixture was stirred at room temperature for several minutes. A drop of concentrated sulfuric acid was added thereto, and the mixture was further stirred for 30 minutes. The reaction solution was neutralized with 2M aqueous sodium hydroxide solution, water (5.0 mL) was further added, and the precipitated solid was collected by suction filtration (yield 96%). The structure of the obtained product was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. The results are shown below.
1 H-NMR (300 MHz, CDCl 3 ): 2.30 (3H, s), 3.68 (3H, s), 3.71 (3H, s), 7.10 (2H, t, J = 8.4 Hz), 7.21 (1H, d , J = 9.0 Hz), 7.23 (1H, d, J = 9.0 Hz), 7.72 (2H, d, J = 8.4 Hz), 7.79 (2H, d, J = 8.1 Hz), 7.97 (1H, d, J = 9.0 Hz), 7.98 (1H, d, J = 9.0 Hz) 8.09 (2H, d, J = 8.1 Hz) ppm
（ここでAcはアセチル基を表す）
13C-NMR (300 MHz, CDCl3) : 21.295, 56.297, 56.346, 77.165, 110.956, 111.162, 120.508, 120.714, 121.117, 125.461, 128.856, 129.977, 130.068, 130.735, 132.540, 136.125, 142.521, 154.133, 156.507, 156.548, 168.779, 170.889, 181.628, 196.512 ppm
IR (KBr) : 3527 (OH), 1696, 1673 (C=O), 1611, 1596 , 1511 (Ar), 1267, 1231 (Ar-O), 1198, 1159 (O-Me) cm-1
MS (FAB) : C28H23O8 ; Exact Mass, 498.1315
[m/z + H+], 499.1427, +3.4 mmu
m.p.= 243.7〜244.4℃
実施例１０
1-(4-ブロモメチルベンゾイル)-8-(4-ニトロベンゾイル)-2,7-ジメトキシナフタレンの合成
(Ac here represents an acetyl group)
13 C-NMR (300 MHz, CDCl 3 ): 21.295, 56.297, 56.346, 77.165, 110.956, 111.162, 120.508, 120.714, 121.117, 125.461, 128.856, 129.977, 130.068, 130.735, 132.540, 136.125, 142.521, 154.133, 156.507, 156.548, 168.779, 170.889, 181.628, 196.512 ppm
IR (KBr): 3527 (OH), 1696, 1673 (C = O), 1611, 1596, 1511 (Ar), 1267, 1231 (Ar-O), 1198, 1159 (O-Me) cm -1
MS (FAB): C 28 H 23 O 8 ; Exact Mass, 498.1315
[m / z + H + ], 499.1427, +3.4 mmu
mp = 243.7-244.4 ° C
Example 10
Synthesis of 1- (4-bromomethylbenzoyl) -8- (4-nitrobenzoyl) -2,7-dimethoxynaphthalene
三方コックを付した30 mL一口ナスフラスコを減圧加熱乾燥後窒素置換し, 4-ニトロ安息香酸 (8.8 mmol, 1.4706 g),五酸化二リン−メタンスルホン酸(17.6 mL)を入れ, 40oCで30分かき混ぜた。そこへ, 2,7-ジメトキシナフタレン(4.0 mmol, 0.7529 g)を加え, さらに30分かき混ぜた。反応溶液を氷水にあけてクロロホルムで抽出(10 mL×3), 有機層を2M水酸化ナトリウム水溶液(10 mL×3),飽和食塩水 (10 mL×3)で洗浄後, 無水硫酸マグネシウムで乾燥させた。エバポレーターで溶媒を留去し, 粗生成物を得た。シリカゲルカラムクロマトグラフィー(トルエン), 再結晶(Et2O)により精製した(収率 34%, 黄色, 針状)。その後, 1H-NMRスペクトルにより構造確認を行い、目的化合物が得られたことを確認した。 The 30 mL single neck eggplant flask equipped with a three-way cock was purged with nitrogen after vacuum heat drying, 4-nitrobenzoic acid (8.8 mmol, 1.4706 g), phosphorus pentoxide - put methanesulfonic acid (17.6 mL), 40 o C Stir for 30 minutes. 2,7-dimethoxynaphthalene (4.0 mmol, 0.7529 g) was added there and stirred for another 30 minutes. The reaction solution was poured into ice water and extracted with chloroform (10 mL × 3) .The organic layer was washed with 2M aqueous sodium hydroxide solution (10 mL × 3) and saturated brine (10 mL × 3), then dried over anhydrous magnesium sulfate. I let you. The solvent was distilled off with an evaporator to obtain a crude product. The product was purified by silica gel column chromatography (toluene) and recrystallization (Et 2 O) (yield 34%, yellow, needle-like). Thereafter, the structure was confirmed by 1 H-NMR spectrum, and it was confirmed that the target compound was obtained.
次いで、三方コック, 窒素風船を付した10 mL一口ナスフラスコを減圧乾燥後, 1-(4-ニトロベンゾイル)-2,7-ジメトキシナフタレン(0.2 mmol, 67 mg), 4-ブロモメチル安息香酸(0.22 mol, 47 mg), 五酸化二リン−メタンスルホン酸(0.44 mL)を入れ, 60≡Cで1.5時間かき混ぜた。反応溶液を氷にあけ, クロロホルム(5.0 mL×3)で抽出し, 2.0 M水酸化ナトリウム水溶液(10 mL×3), 飽和食塩水(10 mL×3)で順次洗浄した後に, 無水硫酸マグネシウムで乾燥した。溶媒をエバポレーターにより留去し, 粗生成物を得た。粗生成物はシリカゲルカラムクロマトグラフ(ヘキサン：酢酸エチル=２：１)により精製した(単離収率82%)。 Next, a 10 mL one-necked eggplant flask equipped with a three-way cock and nitrogen balloon was dried under reduced pressure, and then 1- (4-nitrobenzoyl) -2,7-dimethoxynaphthalene (0.2 mmol, 67 mg), 4-bromomethylbenzoic acid (0.22 mol, 47 mg), diphosphorus pentoxide-methanesulfonic acid (0.44 mL) was added, and the mixture was stirred at 60≡C for 1.5 hours. The reaction solution is poured into ice, extracted with chloroform (5.0 mL × 3), washed sequentially with 2.0 M aqueous sodium hydroxide (10 mL × 3) and saturated brine (10 mL × 3), and then anhydrous magnesium sulfate. Dried. The solvent was removed by an evaporator to obtain a crude product. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) (isolation yield 82%).
得られた生成物は1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。結果を以下に示す。
1H NMR (300 MHz, CDCl3) δ 3.68 (3H, s), 3.71 (3H, s), 4.50 (2H, s) 7.20-7.23 (2H, m), 7.38 (2H, d, J = 8.4 Hz), 7.66 (2H, d, J = 8.4 Hz), 7.86 (2H, d, J = 8.4 Hz), 7.98-8.02 (2H, m), 8.21 (2H, d, J = 8.4 Hz);
13C NMR (75 MHz, CDCl3)δ≡197.0 195.7 156.7 150.0 143.2 142.3 141.9 138.4 133.0 132.6 130.0 129.8 129.5 128.8 125.5 123.4 120.7 119.9 111.3 110.9 56.4 56.3 32.5;
IR (KBr): 1668, 1608, 1512, 1345, 1270, 1229. Elemental anal. calcd (%) for C27H20BrNO6: C, 60.69; H, 3.77. Found: C, 60.63; H, 3.78.
実施例１１
1-(4-ヒドロキシメチルベンゾイル)-8-(4-ニトロベンゾイル)-2,7-ジメトキシナフタレンの合成
The structure of the obtained product was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. The results are shown below.
1 H NMR (300 MHz, CDCl 3 ) δ 3.68 (3H, s), 3.71 (3H, s), 4.50 (2H, s) 7.20-7.23 (2H, m), 7.38 (2H, d, J = 8.4 Hz ), 7.66 (2H, d, J = 8.4 Hz), 7.86 (2H, d, J = 8.4 Hz), 7.98-8.02 (2H, m), 8.21 (2H, d, J = 8.4 Hz);
13 C NMR (75 MHz, CDCl 3 ) δ≡197.0 195.7 156.7 150.0 143.2 142.3 141.9 138.4 133.0 132.6 130.0 129.8 129.5 128.8 125.5 123.4 120.7 119.9 111.3 110.9 56.4 56.3 32.5;
IR (KBr): 1668, 1608, 1512, 1345, 1270, 1229.Elemental anal.calcd (%) for C 27 H 20 BrNO 6 : C, 60.69; H, 3.77. Found: C, 60.63; H, 3.78.
Example 11
Synthesis of 1- (4-hydroxymethylbenzoyl) -8- (4-nitrobenzoyl) -2,7-dimethoxynaphthalene
アリーン冷却管, 塩化カルシウム管を付した10 mL一口ナスフラスコを減圧乾燥後,実施例１０で得た1-(4-ブロモメチルベンゾイル)-8-(4-ニトロベンゾイル)-2,7-ジメトキシナフタレン(0.10 mmol, 54 mg), 1,4-ジオキサン(2.0 mL)を入れ, そこへ0.50 M炭酸カルシウム水溶液(2.0 mL)を加え, 加熱還流下16時間かき混ぜた。反応溶液に塩酸を加え酸性とし, クロロホルム(5.0 mL×3)で抽出し, 飽和食塩水(10 mL×3)で洗浄した後に, 無水硫酸マグネシウムで乾燥した。溶媒をエバポレーターにより留去し, 生成物を得た(単離収率95%)。
得られた生成物は1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。結果を以下に示す。
1H NMR (300 MHz, DMSO-d6)δ≡3.65 (3H, s), 3.67 (3H, s), 4.54 (2H, d, J = 5.7 Hz), 5.34 (1H, t, J = 5.7 Hz), 7.31 (2H, d, J = 9.0 Hz), 7.46 (4H, m), 7.74 (2H, d, J = 9.0 Hz), 8.19≡8.24 (4H, m);
13C NMR (75 MHz, DMSO-d6) ≡≡56.3, 56.4, 62.6, 66.3, 111.6, 111.9, 118.9, 119.9, 123.5, 124.9, 125.9, 128.7, 129.7, 132.6, 133.1, 136.7, 142.6, 148.0, 149.6, 156.2, 156.3, 194.9, 196.3;
IR (KBr): 1667, 1608, 1513, 1346, 1269, 1232.
実施例１２
1-(4-カルボキシベンゾイル)-8-(4-ニトロベンゾイル)-2,7-ジメトキシナフタレンの合成
A 10 mL one-necked eggplant flask equipped with an Allen condenser tube and a calcium chloride tube was dried under reduced pressure, and then 1- (4-bromomethylbenzoyl) -8- (4-nitrobenzoyl) -2,7-dimethoxy obtained in Example 10 was used. Naphthalene (0.10 mmol, 54 mg) and 1,4-dioxane (2.0 mL) were added, 0.50 M calcium carbonate aqueous solution (2.0 mL) was added thereto, and the mixture was stirred for 16 hours with heating under reflux. The reaction solution was acidified with hydrochloric acid, extracted with chloroform (5.0 mL × 3), washed with saturated brine (10 mL × 3), and dried over anhydrous magnesium sulfate. The solvent was distilled off by an evaporator to obtain the product (isolation yield 95%).
The structure of the obtained product was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. The results are shown below.
1 H NMR (300 MHz, DMSO-d 6 ) δ≡3.65 (3H, s), 3.67 (3H, s), 4.54 (2H, d, J = 5.7 Hz), 5.34 (1H, t, J = 5.7 Hz ), 7.31 (2H, d, J = 9.0 Hz), 7.46 (4H, m), 7.74 (2H, d, J = 9.0 Hz), 8.19≡8.24 (4H, m);
13 C NMR (75 MHz, DMSO-d 6 ) ≡≡56.3, 56.4, 62.6, 66.3, 111.6, 111.9, 118.9, 119.9, 123.5, 124.9, 125.9, 128.7, 129.7, 132.6, 133.1, 136.7, 142.6, 148.0, 149.6, 156.2, 156.3, 194.9, 196.3;
IR (KBr): 1667, 1608, 1513, 1346, 1269, 1232.
Example 12
Synthesis of 1- (4-carboxybenzoyl) -8- (4-nitrobenzoyl) -2,7-dimethoxynaphthalene
ジムロー冷却管, 塩化カルシウム管, 滴下漏斗を付した30 mL二口ナスフラスコを減圧乾燥後,実施例１１で得た 1-(4-ヒドロキシメチルベンゾイル)-8-(4-ニトロベンゾイル)-2,7-ジメトキシナフタレン(0.30 mmol, 0.14 g), アセトン(3.6 mL)を入れ, 加熱還流下かき混ぜた。次いで, 過マンガン酸カリウム(0.93 mmol, 0.15 g)の水(2.4 mL)溶液を30分かけて滴下し, 加熱還流下8時間かき混ぜた。反応溶液から固体をろ去し, 得られたろ液に塩酸を加え, 析出した固体を吸引ろ集し, 生成物を得た(単離収率85%)。
得られた生成物は1H-NMRスペクトル, 13C-NMRスペクトル, IR, 元素分析により構造確認を行った。結果を以下に示す。
1H NMR (300 MHz, DMSO-d6)δ≡3.66 (6H, s), 7.51 (2H, d, J = 9.0 Hz), 7.62 (2H, d, J = 8.4 Hz), 7.76 (2H, d, J = 8.7 Hz), 7.93 (2H, d, J = 8.4 Hz), 8.22≡8.27 (4H, m);
13C NMR (75 MHz, DMSO-d6)δ≡56.4, 56.5, 111.8, 112.0, 118.8, 119.4, 123.6, 125.0, 128.2, 128.7, 128.9, 129.0, 129.3, 129.8, 133.1, 133.3, 140.9, 142.6, 149.7, 156.6, 156.6, 195.4, 196.6;
IR (KBr) 1717, 1670, 1609, 1513, 1346, 1270. Elemental anal. calcd (%) for C27H19NO8: C, 66.80; H, 3.95. Found: C, 66.60; H, 3.91.
1- (4-hydroxymethylbenzoyl) -8- (4-nitrobenzoyl) -2 obtained in Example 11 after drying a 30 mL two-necked eggplant flask equipped with a Jimlow condenser, calcium chloride tube, and dropping funnel under reduced pressure , 7-Dimethoxynaphthalene (0.30 mmol, 0.14 g) and acetone (3.6 mL) were added, and the mixture was stirred with heating under reflux. Then, a solution of potassium permanganate (0.93 mmol, 0.15 g) in water (2.4 mL) was added dropwise over 30 minutes, and the mixture was stirred with heating under reflux for 8 hours. The solid was removed from the reaction solution by filtration, hydrochloric acid was added to the obtained filtrate, and the precipitated solid was collected by suction filtration to obtain the product (isolation yield 85%).
The structure of the obtained product was confirmed by 1 H-NMR spectrum, 13 C-NMR spectrum, IR, and elemental analysis. The results are shown below.
1 H NMR (300 MHz, DMSO-d 6 ) δ≡3.66 (6H, s), 7.51 (2H, d, J = 9.0 Hz), 7.62 (2H, d, J = 8.4 Hz), 7.76 (2H, d , J = 8.7 Hz), 7.93 (2H, d, J = 8.4 Hz), 8.22≡8.27 (4H, m);
13 C NMR (75 MHz, DMSO-d 6 ) δ≡56.4, 56.5, 111.8, 112.0, 118.8, 119.4, 123.6, 125.0, 128.2, 128.7, 128.9, 129.0, 129.3, 129.8, 133.1, 133.3, 140.9, 142.6, 149.7, 156.6, 156.6, 195.4, 196.6;
IR (KBr) 1717, 1670, 1609, 1513, 1346, 1270.Elemental anal.calcd (%) for C 27 H 19 NO 8 : C, 66.80; H, 3.95.Found: C, 66.60; H, 3.91.
本発明の非対称型の２，７−ジメトキシナフタレン化合物は反応性に富み、各種芳香族ポリマーへの応用が期待される。 The asymmetric type 2,7-dimethoxynaphthalene compound of the present invention is highly reactive and is expected to be applied to various aromatic polymers.
Claims (2)
で示される２，７−ジメトキシナフタレンと下記一般式（III）
で示される化合物とをＡｌＣｌ3、ＳｂＣｌ5、ＦｅＣｌ3、ＴｅＣｌ2、ＳｎＣｌ4、ＴｉＣｌ4、ＴｅＣｌ4、ＢｉＣｌ3及びＺｎＣｌ2より選ばれる強ルイス酸（ａ）の存在下に反応させることにより下記一般式（IV）
で示される化合物とを上記強ルイス酸（ａ）より相対的に弱いルイス酸（ｂ）の存在下に反応させるか、下記一般式（VI）
で示される化合物とをリン酸系の酸性縮合剤の存在下で直接縮合反応させることを特徴とする下記一般式（Ｉ）で示されるジメトキシナフタレン骨格を有する化合物の製造方法。
2,7-dimethoxynaphthalene represented by the following general formula (III)
Is reacted in the presence of a strong Lewis acid (a) selected from AlCl 3 , SbCl 5 , FeCl 3 , TeCl 2 , SnCl 4 , TiCl 4 , TeCl 4 , BiCl 3 and ZnCl 2. Formula (IV)
In the presence of a Lewis acid (b) that is relatively weaker than the strong Lewis acid (a), or the following general formula (VI)
A method for producing a compound having a dimethoxynaphthalene skeleton represented by the following general formula (I), wherein a direct condensation reaction is carried out in the presence of a phosphoric acid-based acid condensing agent.
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