JPH0128010B2 - - Google Patents
Info
- Publication number
- JPH0128010B2 JPH0128010B2 JP55174974A JP17497480A JPH0128010B2 JP H0128010 B2 JPH0128010 B2 JP H0128010B2 JP 55174974 A JP55174974 A JP 55174974A JP 17497480 A JP17497480 A JP 17497480A JP H0128010 B2 JPH0128010 B2 JP H0128010B2
- Authority
- JP
- Japan
- Prior art keywords
- nitro
- compound
- present
- formaldehyde
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 20
- GAKLFAZBKQGUBO-UHFFFAOYSA-N 2-methyl-3-nitrophenol Chemical class CC1=C(O)C=CC=C1[N+]([O-])=O GAKLFAZBKQGUBO-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- 229940067107 phenylethyl alcohol Drugs 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical class OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims 1
- -1 2-nitro-6-hydroxy-β-phenylethyl Chemical group 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 235000019256 formaldehyde Nutrition 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NLMQHXUGJIAKTH-UHFFFAOYSA-N 4-hydroxyindole Chemical class OC1=CC=CC2=C1C=CN2 NLMQHXUGJIAKTH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- JZQKKSLKJUAGIC-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=C1C=CN2 JZQKKSLKJUAGIC-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
- MGAXYKDBRBNWKT-UHFFFAOYSA-N (5-oxooxolan-2-yl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC(=O)CC1 MGAXYKDBRBNWKT-UHFFFAOYSA-N 0.000 description 1
- XTRDKALNCIHHNI-UHFFFAOYSA-N 2,6-dinitrotoluene Chemical compound CC1=C([N+]([O-])=O)C=CC=C1[N+]([O-])=O XTRDKALNCIHHNI-UHFFFAOYSA-N 0.000 description 1
- PBSZHNXXFIYDBU-UHFFFAOYSA-N 2-methyl-1-nitro-3-phenylmethoxybenzene Chemical compound C1=CC=C([N+]([O-])=O)C(C)=C1OCC1=CC=CC=C1 PBSZHNXXFIYDBU-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003613 toluenes Chemical class 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は一般式
The present invention is based on the general formula
【式】
（式中R1はベンジル基を表わす）で表わされ
る２―ニトロ―６―ヒドロキシ―β―フエニルエ
チルアルコール誘導体に関する。
〔〕式で表わされる本発明化合物は４―置換
インドール類を製造する為の中間体として非常に
重要である。
すなわち式〔〕の新規な化合物をそのままあ
るいは一度アミノ化合物に誘導した後、触媒の存
在下加熱することによつて容易にかつ高収率で４
―ヒドロキシインドール及びその誘導体へ導くこ
とが出来る。
４ー置換インドール類は医薬又は農薬の合成原
料として有用である，例えば４―ヒドロキシイン
ドールは、抗不整脈剤及び降圧剤として賞用され
ているピンドロール〔４―（２―ヒドロキシ―３
―イソプロピルアミノ―プロポキシ）インドー
ル〕の合成原料として使用される。
本発明になる化合物〔〕は、一般式〔〕で
表わされる２―ニトロ―６―ヒドロキシトルエン
誘導体をホルムアルデヒド類と反応させることに
よつて、得ることが出来る。
置換トルエンをホルムアルデヒド類と反応させ
て、β―フエニルエチルアルコール類を製造する
ことは知られている。しかし本発明化合物につい
てはまつたく知られていない。
本発明者らは鋭意研究を続けた結果、２―ニト
ロ―６―ヒドロキシトルエン誘導体を、ホルムア
ルデヒド類と反応させることにより極めて高収率
で本発明化合物〔〕が得られることを見出し本
発明方法を完成した。原料である一般式〔〕の
２―ニトロ―６―ヒドロキシトルエン誘導体は工
業的に極めて安価に入手出来る２，６ジニトロト
ルエンを出発原料として容易に得ることが出来
る。
本発明化合物の製造方法は非プロトン性極性溶
媒中に、２―ニトロ―６―ヒドロキシトルエン誘
導体を溶解し、触媒としてアルカリ金属アルコキ
シドを加えた後ホルムアルデヒド類を加え反応さ
せることにより好適に実施される。
非プロトン性極性溶媒としてはジメチルホルム
アミド、ジメチルアセトアミド、ジメチルスルホ
キシド、ジメチルスルホン、ヘキサメチルホスホ
ルアミドなどを挙げることが出来る。特にはジメ
チルスルホキシド、ジメチルホルムアミドが好ま
しい。
アルカリ金属アルコキシドとしては低級アルコ
ール及びフエノール類のアルカリ金属塩が使用出
来る。具体的にはメタノール、エタノール、フエ
ノールのアルカリ金属塩例えばナトリウムメトキ
シド、ナトリウムエトキシド、ナトリウムフエノ
キシドを挙げることが出来る。
アルコキシドの使用量は原料である一般式
〔〕の化合物に対して１ないし50モル％使用す
ればよい。
本発明の方法で使用するホルムアルデヒド類と
しては、ホルムアルデヒドあるいはパラホルムア
ルデヒド、ポリオキシメチレンのように反応条件
下で容易に分解してホルムアルデヒドを発生する
ホルムアルデヒドの縮重合体を挙げることが出来
る。
これらホルムアルデヒド類の使用量は一般式
〔〕で表わされる化合物に対して0.2ないし1.5
倍モルの範囲である。
反応温度は０℃ないし100℃好ましくは10℃な
いし70℃において実施される。
反応時間は特に限定されるべきものではない
が、一般には、0.2ないし２時間反応を行なわし
めるのが収率上好ましい。反応終了後は、反応混
合物から溶媒を留去した後、水を加え新たに別の
溶媒を用いて目的化合物をとり出す。
次に本発明方法を実施例によりさらに具体的に
説明する。
実施例 １
２―ニトロ―６―ベンジルオキシ―トルエン
9.8ｇ（40ミリモル）をジメチルスルホキシド100
mlに溶解せしめ、パラホルムアルデヒド2.2ｇ
（70ミリモル）とナトリウムメトキシド0.75ｇ
（14ミリモル）を加え、撹拌しながら25℃で30分
反応させた。反応終了後、溶媒を留去し、水を
100ml加え、クロロホルムで抽出し（40ml×３
回）、水洗（60ml×１回）した。無水硫酸ナトリ
ウムで乾燥後、減圧濃縮し残留物12.1ｇを得た。
これをクロマトグラフイー（シリカゲル、クロロ
ホルム）で分離精製し、２―ニトロ―６―ベンジ
ルオキシ―β―フエニルエチルアルコール10.4ｇ
を得た。収率95％この化合物の物性を示せば次の
通りである。
IR(KBr.cm-1)；3350cm-1(-OH)
1520cm-1，1350cm-1(-NO2)
MS(m/e)；273(M+)
NMR(CDCl3)
δ(ppm)；2.95〜3.20 （2H，ｔ）
3.70〜3.93 （2H，ｔ）
5.04 （2H，ｓ）
7.0〜7.33 （8H）The present invention relates to a 2-nitro-6-hydroxy-β-phenylethyl alcohol derivative represented by the formula: (wherein R 1 represents a benzyl group). The compound of the present invention represented by the formula [] is very important as an intermediate for producing 4-substituted indoles. That is, by heating the novel compound of formula [] as it is or once deriving it into an amino compound and then heating it in the presence of a catalyst, 4 can be easily and in high yield.
-Can lead to hydroxyindoles and their derivatives. 4-Substituted indoles are useful as raw materials for the synthesis of medicines or agricultural chemicals. For example, 4-hydroxyindole is used as an antiarrhythmic agent and antihypertensive agent, such as pindolol [4-(2-hydroxy-3
-isopropylamino-propoxy)indole] is used as a synthetic raw material. The compound [] of the present invention can be obtained by reacting a 2-nitro-6-hydroxytoluene derivative represented by the general formula [] with formaldehyde. It is known to react substituted toluene with formaldehyde to produce β-phenylethyl alcohols. However, little is known about the compound of the present invention. As a result of intensive research, the present inventors discovered that the compound of the present invention [] could be obtained in extremely high yield by reacting a 2-nitro-6-hydroxytoluene derivative with formaldehydes, and developed the method of the present invention. completed. The 2-nitro-6-hydroxytoluene derivative of the general formula [], which is a raw material, can be easily obtained using 2,6 dinitrotoluene, which is industrially available at extremely low cost, as a starting material. The method for producing the compound of the present invention is suitably carried out by dissolving a 2-nitro-6-hydroxytoluene derivative in an aprotic polar solvent, adding an alkali metal alkoxide as a catalyst, and then adding formaldehyde for reaction. . Examples of the aprotic polar solvent include dimethylformamide, dimethylacetamide, dimethylsulfoxide, dimethylsulfone, and hexamethylphosphoramide. Particularly preferred are dimethyl sulfoxide and dimethyl formamide. As the alkali metal alkoxide, lower alcohols and alkali metal salts of phenols can be used. Specific examples include methanol, ethanol, and alkali metal salts of phenol, such as sodium methoxide, sodium ethoxide, and sodium phenoxide. The amount of alkoxide to be used may be 1 to 50 mol % based on the compound of the general formula [] as a raw material. Formaldehydes used in the method of the present invention include formaldehyde, paraformaldehyde, and formaldehyde condensation polymers that easily decompose under reaction conditions to generate formaldehyde, such as polyoxymethylene. The amount of formaldehyde used is 0.2 to 1.5 per the compound represented by the general formula [].
It is in the double molar range. The reaction temperature is 0°C to 100°C, preferably 10°C to 70°C. Although the reaction time is not particularly limited, it is generally preferable to carry out the reaction for 0.2 to 2 hours in terms of yield. After the reaction is completed, the solvent is distilled off from the reaction mixture, water is added, and a new solvent is used to take out the target compound. Next, the method of the present invention will be explained in more detail with reference to Examples. Example 1 2-nitro-6-benzyloxy-toluene
9.8 g (40 mmol) of dimethyl sulfoxide 100
2.2 g of paraformaldehyde dissolved in ml
(70 mmol) and 0.75 g of sodium methoxide
(14 mmol) was added, and the mixture was reacted at 25°C for 30 minutes with stirring. After the reaction is complete, the solvent is distilled off and the water is removed.
Add 100ml and extract with chloroform (40ml x 3
2 times) and washed with water (60 ml x 1 time). After drying over anhydrous sodium sulfate, it was concentrated under reduced pressure to obtain 12.1 g of a residue.
This was separated and purified by chromatography (silica gel, chloroform), and 10.4 g of 2-nitro-6-benzyloxy-β-phenylethyl alcohol was used.
I got it. Yield: 95% The physical properties of this compound are as follows. IR(KBr.cm -1 ); 3350cm -1 (-OH) 1520cm -1 , 1350cm -1 (-NO 2 ) MS(m/e); 273(M + ) NMR(CDCl 3 ) δ(ppm); 2.95~3.20 (2H, t) 3.70~3.93 (2H, t) 5.04 (2H, s) 7.0~7.33 (8H)
Claims (1)
―β―フエニルエチルアルコール誘導体。 ２ 一般式 （式中R1は上記と同じ）で表わされる２―ニ
トで表わされる２―ニトロ―６―ヒドロキシトル
エン誘導体をホルムアルデヒド類と反応させるこ
とを特徴とする２―ニトロ―６―ヒドロキシ―β
―フエニルエチルアルコール誘導体の製造法。[Claims] 1. General formula (In the formula, R 1 represents a benzyl group) A compound 2-nitro-6-hydroxy-β-phenylethyl alcohol derivative. 2 General formula 2-nitro-6-hydroxy-β, which is characterized by reacting a 2-nitro-6-hydroxytoluene derivative represented by 2-nito (wherein R 1 is the same as above) with formaldehyde.
-Process for producing phenylethyl alcohol derivatives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55174974A JPS5799558A (en) | 1980-12-11 | 1980-12-11 | 2-nitro-6-hydroxy-beta-phenylethyl alcoholic derivative and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55174974A JPS5799558A (en) | 1980-12-11 | 1980-12-11 | 2-nitro-6-hydroxy-beta-phenylethyl alcoholic derivative and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5799558A JPS5799558A (en) | 1982-06-21 |
| JPH0128010B2 true JPH0128010B2 (en) | 1989-05-31 |
Family
ID=15987992
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP55174974A Granted JPS5799558A (en) | 1980-12-11 | 1980-12-11 | 2-nitro-6-hydroxy-beta-phenylethyl alcoholic derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5799558A (en) |
-
1980
- 1980-12-11 JP JP55174974A patent/JPS5799558A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5799558A (en) | 1982-06-21 |
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