JP4984676B2 - Preparation of aniline having benzyloxy group - Google Patents

Preparation of aniline having benzyloxy group Download PDF

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JP4984676B2
JP4984676B2 JP2006173562A JP2006173562A JP4984676B2 JP 4984676 B2 JP4984676 B2 JP 4984676B2 JP 2006173562 A JP2006173562 A JP 2006173562A JP 2006173562 A JP2006173562 A JP 2006173562A JP 4984676 B2 JP4984676 B2 JP 4984676B2
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platinum
aniline
aralkyloxy
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JP2007051128A (en
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繁栄 西野
秀好 島
広行 小田
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Ube Corp
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本発明は、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼンと水素とを反応させ、脱アラルキル化又は脱ヘテロアラルキル化をさせることなく、アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンを製造する方法に関する。アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンは、例えば、医薬・農薬等の原料や合成中間体として有用な化合物である。   The present invention relates to a method for producing an aniline having an aralkyloxy or heteroaralkyloxy group by reacting nitrobenzene having an aralkyloxy or heteroaralkyloxy group with hydrogen, without causing dearalkylation or deheteroaralkylation. Aniline having an aralkyloxy or heteroaralkyloxy group is a useful compound as a raw material for pharmaceuticals, agricultural chemicals, etc., or a synthetic intermediate.

従来、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼンと水素とを反応させ、アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンを製造する方法としては、例えば、塩化スズを使用する方法(例えば、非特許文献1参照)、鉄及び塩化鉄を使用する方法(例えば、非特許文献2参照)や鉄及び塩酸を使用する方法(例えば、非特許文献3参照)が開示されている。しかしながら、これらの方法では、金属類を反応液から取り除くために煩雑な操作を行わなければならず、工業的に好適なアラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンの製法としては不利であった。
J.Org.Chem.,66(8),2881(2001) J.Med.Chem.,45(17),3772(2002) Tetrahedron,51(19),5617(1995)
Conventionally, as a method for producing aniline having an aralkyloxy or heteroaralkyloxy group by reacting nitrobenzene having an aralkyloxy or heteroaralkyloxy group with hydrogen, for example, a method using tin chloride (for example, non-patent literature) 1), a method using iron and iron chloride (for example, see Non-Patent Document 2) and a method using iron and hydrochloric acid (for example, see Non-Patent Document 3). However, in these methods, complicated operations must be performed to remove metals from the reaction solution, which is disadvantageous as an industrially suitable method for producing anilines having an aralkyloxy or heteroaralkyloxy group.
J. Org. Chem., 66 (8), 2881 (2001) J. Med. Chem., 45 (17), 3772 (2002) Tetrahedron, 51 (19), 5617 (1995)

本発明の課題は、即ち、上記問題点を解決し、温和な条件下、簡便な方法によって、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼンと水素とを反応させ、脱アラルキル化又は脱ヘテロアラルキル化をさせることなく、アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンを提供することにある。   The object of the present invention is to solve the above-mentioned problems, by reacting nitrobenzene having an aralkyloxy or heteroaralkyloxy group with hydrogen by a simple method under mild conditions to dearalkylate or deheteroaralkylate. An object of the present invention is to provide an aniline having an aralkyloxy or heteroaralkyloxy group.

本発明の課題は、金属触媒の存在下、一般式(1)   The subject of this invention is general formula (1) in presence of a metal catalyst.

(式中、Arは、置換基を有していても良いアリール基又はヘテロアリール基、Zは、置置換基を有していても良い二価の芳香族基を示す。)
で示されるアラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼンと水素とを反応させることを特徴とする、一般式(2)
(In the formula, Ar represents an aryl group or heteroaryl group which may have a substituent, and Z represents a divalent aromatic group which may have a substituent.)
A nitrobenzene having a aralkyloxy or heteroaralkyloxy group represented by formula (2) is reacted with hydrogen.

(式中、Ar及びZは、前記と同義である。)
でアラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンの製法によって解決される。
(In the formula, Ar and Z are as defined above.)
This is solved by a process for preparing anilines having an aralkyloxy or heteroaralkyloxy group.

本発明により、温和な条件下、簡便な方法によって、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼンと水素とを反応させ、脱アラルキル化又は脱ヘテロアラルキル化をさせることなく、アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンを提供することができる。   According to the present invention, nitrobenzene having an aralkyloxy or heteroaralkyloxy group is reacted with hydrogen by a simple method under mild conditions, without causing aralkyloxy or heteroaralkyloxylation without dearalkylation or deheteroaralkylation. An aniline having a group can be provided.

本発明の反応で使用するアラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼンは、前記の一般式(1)で示される。その一般式(1)において、Arは、置換基を有していても良いアリール基又はヘテロアリール基であり、アリール基としては、例えば、フェニル基、p-トリル基、ナフチル基、アントリル基等;ヘテロアリール基としては、例えば、フリル基、チエニル基、ピロリル基、オキサゾリル基、ピリジル基、キノリニル基、カルバゾリル基等が挙げられる。なお、これらの基は、各種異性体を含む。   The nitrobenzene having an aralkyloxy or heteroaralkyloxy group used in the reaction of the present invention is represented by the general formula (1). In the general formula (1), Ar is an aryl group or heteroaryl group which may have a substituent, and examples of the aryl group include a phenyl group, a p-tolyl group, a naphthyl group, and an anthryl group. The heteroaryl group includes, for example, a furyl group, a thienyl group, a pyrrolyl group, an oxazolyl group, a pyridyl group, a quinolinyl group, and a carbazolyl group. These groups include various isomers.

前記のアリール基又はヘテロアリール基は、置換基を有していても良い。その置換基としては、炭素原子を介して出来る置換基、酸素原子を介して出来る置換基、窒素原子を介して出来る置換基、硫黄原子を介して出来る置換基、ハロゲン原子等が挙げられる。   The aryl group or heteroaryl group may have a substituent. Examples of the substituent include a substituent formed through a carbon atom, a substituent formed through an oxygen atom, a substituent formed through a nitrogen atom, a substituent formed through a sulfur atom, and a halogen atom.

前記炭素原子を介して出来る置換基としては、例えば、メチル基、エチル基、プロピル基、ブチル基、ペンチル基、ヘキシル基等のアルキル基;シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基、シクロヘプチル基等のシクロアルキル基;ビニル基、アリル基、プロペニル基、シクロプロペニル基、シクロブテニル基、シクロペンテニル基等のアルケニル基;キノリル基、ピリジル基、ピロリジル基、ピロリル基、フリル基、チエニル基等の複素環基;フェニル基、トリル基、フルオロフェニル基、キシリル基、ビフェニリル基、ナフチル基、アントリル基、フェナントリル基等のアリール基;アセチル基、プロピオニル基、アクリロイル基、ピバロイル基、シクロヘキシルカルボニル基、ベンゾイル基、ナフトイル基、トルオイル基等のアシル基(アセタール化されていても良い);カルボキシル基;メトキシカルボニル基、エトキシカルボニル基等のアルコキシカルボニル基;フェノキシカルボニル基等のアリールオキシカルボニル基;トリフルオロメチル基等のハロゲン化アルキル基;シアノ基が挙げられる。なお、これらの基は、各種異性体を含む。   Examples of the substituent formed through the carbon atom include alkyl groups such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group; a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cyclo group. Cycloalkyl groups such as heptyl group; Alkenyl groups such as vinyl group, allyl group, propenyl group, cyclopropenyl group, cyclobutenyl group, cyclopentenyl group; quinolyl group, pyridyl group, pyrrolidyl group, pyrrolyl group, furyl group, thienyl group, etc. An aryl group such as phenyl group, tolyl group, fluorophenyl group, xylyl group, biphenylyl group, naphthyl group, anthryl group, phenanthryl group; acetyl group, propionyl group, acryloyl group, pivaloyl group, cyclohexylcarbonyl group, Benzoyl group, naphthoyl Group, acyl group such as toluoyl group (may be acetalized); carboxyl group; alkoxycarbonyl group such as methoxycarbonyl group and ethoxycarbonyl group; aryloxycarbonyl group such as phenoxycarbonyl group; trifluoromethyl group and the like A halogenated alkyl group; and a cyano group. These groups include various isomers.

前記酸素原子を介して出来る置換基としては、例えば、ヒドロキシル基;メトキシル基、エトキシル基、プロポキシル基、ブトキシル基、ペンチルオキシル基、ヘキシルオキシル基、ヘプチルオキシル基、ベンジルオキシル基等のアルコキシル基;フェノキシル基、トルイルオキシル基、ナフチルオキシル基等のアリールオキシル基が挙げられる。なお、これらの基は、各種異性体を含む。   Examples of the substituent formed through the oxygen atom include a hydroxyl group; an alkoxyl group such as a methoxyl group, an ethoxyl group, a propoxyl group, a butoxyl group, a pentyloxyl group, a hexyloxyl group, a heptyloxyl group, and a benzyloxyl group; Aryloxyl groups such as phenoxyl group, toluyloxyl group, naphthyloxyl group and the like can be mentioned. These groups include various isomers.

本発明の反応において使用する金属触媒としては、例えば、白金/炭素、硫化白金/炭素、パラジウム−白金/炭素、酸化白金、白金/アルミナ及びロジウム/炭素が挙げられるが、硫黄により活性を低下させた白金/炭素(例えば、硫化白金/炭素)が好適に使用される。なお、これらの金属触媒は、単独又は二種以上を混合して使用しても良く、含水品でも無水品でも構わない。 Examples of the metal catalyst used in the reaction of the present invention include platinum / carbon, platinum sulfide / carbon, palladium-platinum / carbon, platinum oxide , platinum / alumina, and rhodium / carbon. Platinum / carbon (for example, platinum sulfide / carbon) is preferably used. In addition, these metal catalysts may be used individually or in mixture of 2 or more types, and may be a water-containing product or an anhydrous product.

前記金属触媒の使用量は、金属原子換算で、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼン1gに対して、好ましくは0.1〜1000mg、更に好ましくは0.5〜500mgである。   The amount of the metal catalyst used is preferably 0.1 to 1000 mg, more preferably 0.5 to 500 mg, based on 1 g of nitrobenzene having an aralkyloxy or heteroaralkyloxy group, in terms of metal atoms.

本発明の反応で使用する水素の量は、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼン1モルに対して、好ましくは2〜50モル、更に好ましくは2〜10モルである。   The amount of hydrogen used in the reaction of the present invention is preferably 2 to 50 mol, more preferably 2 to 10 mol, per 1 mol of nitrobenzene having an aralkyloxy or heteroaralkyloxy group.

本発明の反応は溶媒の存在、非存在下で行うことができるが、使用する溶媒としては、反応を阻害するものでなければ特に限定されず、例えば、水;メタノール、エタノール、イソプロピルアルコール、n-ブチルアルコール、t-ブチルアルコール等のアルコール類;酢酸メチル、酢酸エチル、プロピオン酸メチル等のカルボン酸エステル類;ベンゼン、トルエン、キシレン、メシチレン等の芳香族炭化水素類;ジエチルエーテル、ジメトキシエタン、テトラヒドロフラン、ジオキサン、ジイソプロピルエーテル等のエーテル類が挙げられるが、好ましくはエステル類、エーテル類が使用される。なお、これらの溶媒は、単独又は二種以上を混合して使用しても良い。   The reaction of the present invention can be carried out in the presence or absence of a solvent, but the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, water; methanol, ethanol, isopropyl alcohol, n -Alcohols such as butyl alcohol and t-butyl alcohol; carboxylic acid esters such as methyl acetate, ethyl acetate and methyl propionate; aromatic hydrocarbons such as benzene, toluene, xylene and mesitylene; diethyl ether, dimethoxyethane, Ethers such as tetrahydrofuran, dioxane, diisopropyl ether and the like can be mentioned, and esters and ethers are preferably used. In addition, you may use these solvents individually or in mixture of 2 or more types.

前記溶媒の使用量は、反応液の均一性や攪拌性等によって適宜調節するが、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼン1gに対して、好ましくは0〜100g、更に好ましくは0〜30gである。   The amount of the solvent used is appropriately adjusted depending on the uniformity and stirring properties of the reaction solution, but is preferably 0 to 100 g, more preferably 0 to 30 g based on 1 g of nitrobenzene having an aralkyloxy or heteroaralkyloxy group. is there.

本発明の反応は、例えば、水素ガスの存在下(不活性ガスで希釈されていても良い)にて、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼン、金属触媒及び溶媒を混合して攪拌させる等の方法によって行われる。その際の反応温度は、好ましくは0〜300℃、更に好ましくは20〜200℃であり、反応圧力は、好ましくは0.1〜10MPa、更に好ましくは0.1〜2MPaである。   In the reaction of the present invention, for example, nitrobenzene having an aralkyloxy or heteroaralkyloxy group, a metal catalyst and a solvent are mixed and stirred in the presence of hydrogen gas (which may be diluted with an inert gas). It is done by the method. The reaction temperature at that time is preferably 0 to 300 ° C., more preferably 20 to 200 ° C., and the reaction pressure is preferably 0.1 to 10 MPa, more preferably 0.1 to 2 MPa.

本発明の反応によって、アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンが得られるが、これは、反応終了後、例えば、中和、抽出、濾過、濃縮、蒸留、再結晶、晶析、カラムクロマトグラフィー等の一般的な方法によって単離・精製される。   By the reaction of the present invention, an aniline having an aralkyloxy or heteroaralkyloxy group is obtained, which can be obtained, for example, after neutralization, extraction, filtration, concentration, distillation, recrystallization, crystallization, column chromatography. It is isolated and purified by a general method such as

次に、実施例を挙げて本発明を具体的に説明するが、本発明の範囲はこれらに限定されるものではない。   Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

参考例1(2-ベンジルオキシアニリンの合成)
攪拌装置、温度計、還流冷却器及び水素を充填した風船を備えた内容積100mlのガラス製容器に、2−ベンジルオキシニトロベンゼン3.0g(13.09mmol)、3質量%硫化白金/炭素(50%含水品)0.15g及び酢酸ブチル30mlを加え、水素雰囲気にて、攪拌しながら60℃で3時間反応させた。反応終了後、反応液を濾過し、濾液を減圧下で濃縮した。濃縮物をシリカゲルカラムクロマトグラフィーで精製(展開溶媒;ヘキサン:酢酸エチル=4:1(容量比))し、茶色液体として、2-ベンジルオキシアニリン2.46gを得た(単離収率;94.6%)。
2-ベンジルオキシアニリンの物性値は以下の通りであった。
Reference Example 1 (Synthesis of 2-benzyloxyaniline)
In a glass container with an internal volume of 100 ml equipped with a stirrer, thermometer, reflux condenser and balloon filled with hydrogen, 3.0 g (13.09 mmol) of 2-benzyloxynitrobenzene , 3 mass% platinum sulfide / carbon (50% water content) Product) 0.15 g and 30 ml of butyl acetate were added and reacted in a hydrogen atmosphere at 60 ° C. for 3 hours with stirring. After completion of the reaction, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (volume ratio)) to obtain 2.46 g of 2-benzyloxyaniline as a brown liquid (isolated yield; 94.6% ).
The physical properties of 2-benzyloxyaniline were as follows.

1H-NMR(CDCl3,δ(ppm));3.85(2H,brS)、5.11(2H,S)、6.70〜6.90(3H,m)、7.32〜7.48(4H,m)
CI-MS(m/e);200(M+)
1 H-NMR (CDCl 3 , δ (ppm)); 3.85 (2H, brS), 5.11 (2H, S), 6.70-6.90 (3H, m), 7.32-7.48 (4H, m)
CI-MS (m / e); 200 (M +)

参考例2(3-ベンジルオキシアニリンの合成)
参考例1において、2-ベンジルオキシニトロベンゼンを、3-ベンジルオキシニトロベンゼンに変えたこと以外は、参考例1と同様に反応を行った。その結果、ベージュ色固体として、3-ベンジルオキシアニリン1.80gを得た(単離収率;69.2%)。
3-ベンジルオキシアニリンの物性値は以下の通りであった。
Reference Example 2 (Synthesis of 3-benzyloxyaniline)
The reaction was performed in the same manner as in Reference Example 1 except that 2-benzyloxynitrobenzene was changed to 3-benzyloxynitrobenzene in Reference Example 1. As a result, 1.80 g of 3-benzyloxyaniline was obtained as a beige solid (isolation yield: 69.2%).
The physical properties of 3-benzyloxyaniline were as follows.

1H-NMR(CDCl3,δ(ppm));3.66(2H,brs)、5.04(2H,s)、6.31〜6.44(3H,m)、7.05〜7.11(1H,m)、7.30〜7.46(5H,m)
CI-MS(m/e);200(M+)
1 H-NMR (CDCl 3 , δ (ppm)); 3.66 (2H, brs), 5.04 (2H, s), 6.31 to 6.44 (3H, m), 7.05 to 7.11 (1H, m), 7.30 to 7.46 ( 5H, m)
CI-MS (m / e); 200 (M +)

参考例3(4-ベンジルオキシアニリンの合成)
参考例1において、2-ベンジルオキシニトロベンゼンを、4-ベンジルオキシニトロベンゼンに変えたこと以外は、参考例1と同様に反応を行った。その結果、茶色固体として、4-ベンジルオキシアニリン2.29gを得た(単離収率;88.0%)。
4-ベンジルオキシアニリンの物性値は以下の通りであった。
Reference Example 3 (Synthesis of 4-benzyloxyaniline)
The reaction was performed in the same manner as in Reference Example 1 except that 2-benzyloxynitrobenzene was changed to 4-benzyloxynitrobenzene in Reference Example 1. As a result, 2.29 g of 4-benzyloxyaniline was obtained as a brown solid (isolation yield; 88.0%).
The physical properties of 4-benzyloxyaniline were as follows.

1H-NMR(CDCl3,δ(ppm));3.44(2H,brs)、5.01(2H,s)、6.63〜6.68(2H,m)、6.81〜6.86(2H,m)、7.30〜6.68(5H,m)
CI-MS(m/e);200(M+)
1 H-NMR (CDCl 3 , δ (ppm)); 3.44 (2H, brs), 5.01 (2H, s), 6.63 to 6.68 (2H, m), 6.81 to 6.86 (2H, m), 7.30 to 6.68 ( 5H, m)
CI-MS (m / e); 200 (M +)

参考例4(4-(3-フルオロベンジルオキシ)-3-クロロアニリンの合成)
攪拌装置、温度計、還流冷却器及び水素を充填した風船を備えた内容積100mlのガラス製容器に、4-(3-フルオロベンジルオキシ)-3-クロロニトロベンゼン3.0g(10.65mmol)、3質量%硫化白金/炭素(50%含水品)0.15g及び酢酸ブチル30mlを加え、水素雰囲気にて、攪拌しながら60℃で3時間反応させた。反応終了後、反応液を濾過し、濾液を減圧下で濃縮した。濃縮物をシリカゲルカラムクロマトグラフィーで精製(展開溶媒;ヘキサン:酢酸エチル=4:1(容量比))し、茶色固体として、4-(3-フルオロベンジルオキシ)-3-クロロアニリン2.36gを得た(単離収率;88.0%)。
4-(3-フルオロベンジルオキシ)-3-クロロアニリンの物性値は以下の通りであった。
Reference Example 4 (Synthesis of 4- (3-fluorobenzyloxy) -3-chloroaniline)
In a 100 ml glass container equipped with a stirrer, thermometer, reflux condenser and balloon filled with hydrogen, 3.0 g (10.65 mmol) of 4- (3-fluorobenzyloxy) -3-chloronitrobenzene, 3 mass % Platinum sulfide / carbon (50% water-containing product) 0.15 g and butyl acetate 30 ml were added, and the mixture was reacted at 60 ° C. for 3 hours in a hydrogen atmosphere with stirring. After completion of the reaction, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (volume ratio)) to obtain 2.36 g of 4- (3-fluorobenzyloxy) -3-chloroaniline as a brown solid. (Isolated yield; 88.0%).
The physical properties of 4- (3-fluorobenzyloxy) -3-chloroaniline were as follows.

1H-NMR(CDCl3,δ(ppm));3.51(2H,brs)、5.04(2H,s)、6.49〜6.53(1H,m)、6.77〜6.80(2H,m)、6.97〜7.04(1H,m)、7.19〜7.23(2H,m)、7.31〜7.38(1H,m)
CI-MS(m/e);252(M+)
1 H-NMR (CDCl 3 , δ (ppm)); 3.51 (2H, brs), 5.04 (2H, s), 6.49 to 6.53 (1H, m), 6.77 to 6.80 (2H, m), 6.97 to 7.04 ( 1H, m), 7.19-7.23 (2H, m), 7.31-7.38 (1H, m)
CI-MS (m / e); 252 (M +)

参考例5(3-アミノ-2-ベンジルオキシピリジンの合成)
攪拌装置、温度計及び還流管を備えた内容積100mlのガラス製容器に、3-ニトロ-2-ベンジルオキシピリジン2.0g(8.68mmol)、3質量%硫化白金/炭素(50%含水品)0.10g及び酢酸ブチル20mlを加え、水素雰囲気にて、攪拌しながら60℃で3時間反応させた。反応終了後、反応液を濾過し、濾液を減圧下で濃縮した。濃縮物をシリカゲルカラムクロマトグラフィーで精製(展開溶媒;ヘキサン:酢酸エチル=1:1(容量比))し、茶色固体として、3-アミノ-2-ベンジルオキシピリジン0.80gを得た(単離収率;46.2%)。
3-アミノ-2-ベンジルオキシピリジンの物性値は以下の通りであった。
Reference Example 5 (Synthesis of 3-amino-2-benzyloxypyridine)
In a glass container with an internal volume of 100 ml equipped with a stirrer, thermometer and reflux tube, 2.0 g (8.68 mmol) of 3-nitro-2-benzyloxypyridine, 3% by mass of platinum sulfide / carbon (50% water-containing product) 0.10 g and 20 ml of butyl acetate were added, and the mixture was reacted at 60 ° C. for 3 hours with stirring in a hydrogen atmosphere. After completion of the reaction, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 1: 1 (volume ratio)) to obtain 0.80 g of 3-amino-2-benzyloxypyridine as a brown solid (isolated product). Rate; 46.2%).
The physical properties of 3-amino-2-benzyloxypyridine were as follows.

1H-NMR(CDCl3,δ(ppm));4.28(2H,brs)、5.16(2H,s)、6.01〜6.06(1H,m)、6.49〜6.52(1H,m)、6.70〜6.73(1H,m)、7.24〜7.36(5H,m)
CI-MS(m/e);201(M+)
1 H-NMR (CDCl 3 , δ (ppm)); 4.28 (2H, brs), 5.16 (2H, s), 6.01 to 6.06 (1H, m), 6.49 to 6.52 (1H, m), 6.70 to 6.73 ( 1H, m), 7.24-7.36 (5H, m)
CI-MS (m / e); 201 (M +)

実施例6(2-アミノ-4-ベンジルオキシ-5-メトキシ安息香酸メチルの合成)
攪拌装置、温度計、還流冷却器及び水素を充填した風船を備えた内容積20mlのガラス製容器に、4-ベンジルオキシ-5-メトキシ-2-ニトロ安息香酸メチル4.0g(12.6mmol)、3質量%硫化白金/炭素(60%含水品)0.2g及びジメトキシエタン20mlを加え、水素雰囲気にて、攪拌しながら室温で7時間反応させた。反応終了後、反応液を10日放置した後、濾過し、反応液を減圧下で濃縮して、薄茶色固体として、2-アミノ-4-ベンジルオキシ-5-メトキシ安息香酸メチル3.17gを得た(単離収率;87%)。
2-アミノ-4-ベンジルオキシ-5-メトキシ安息香酸メチルの物性値は以下の通りであった。
Example 6 (Synthesis of methyl 2-amino-4-benzyloxy-5-methoxybenzoate)
In a glass container with an internal volume of 20 ml equipped with a stirrer, thermometer, reflux condenser and balloon filled with hydrogen, 4.0 g (12.6 mmol) of methyl 4-benzyloxy-5-methoxy-2-nitrobenzoate, 3 0.2% by mass of platinum sulfide / carbon (60% water-containing product) and 20 ml of dimethoxyethane were added, and the mixture was reacted at room temperature for 7 hours with stirring in a hydrogen atmosphere. After completion of the reaction, the reaction solution is allowed to stand for 10 days and then filtered, and the reaction solution is concentrated under reduced pressure to obtain 3.17 g of methyl 2-amino-4-benzyloxy-5-methoxybenzoate as a light brown solid. (Isolation yield; 87%).
The physical properties of methyl 2-amino-4-benzyloxy-5-methoxybenzoate were as follows.

1H-NMR(CDCl3,δ(ppm));3.81(3H,s)、3.83(3H,s)、5.09(2H,s)、5.37(2H,brs)、6.15(1H,s)、7.31〜7.41(6H,m)
CI-MS(m/e);287(M+)
1 H-NMR (CDCl 3 , δ (ppm)); 3.81 (3H, s), 3.83 (3H, s), 5.09 (2H, s), 5.37 (2H, brs), 6.15 (1H, s), 7.31 ~ 7.41 (6H, m)
CI-MS (m / e); 287 (M +)

実施例7(2-アミノ-4-ベンジルオキシ-5-メトキシ安息香酸メチルの合成)
実施例6において、3質量%硫化白金/炭素を、5質量%白金/アルミナに変えたこと以外は、実施例6と同様に反応を行った。その結果、2-アミノ-4-ベンジルオキシ-5-メトキシ安息香酸メチルが2.17g生成していた(反応収率;54.6%)。
Example 7 (Synthesis of methyl 2-amino-4-benzyloxy-5-methoxybenzoate)
In Example 6, the reaction was performed in the same manner as in Example 6 except that 3% by mass of platinum sulfide / carbon was changed to 5% by mass of platinum / alumina. As a result, 2.17 g of methyl 2-amino-4-benzyloxy-5-methoxybenzoate was formed (reaction yield: 54.6%).

実施例8(2-アミノ-4-ベンジルオキシ-5-メトキシ安息香酸メチルの合成)
実施例6において、3質量%硫化白金/炭素を、5質量%ロジウム/炭素に変えたこと以外は、実施例6と同様に反応を行った。その結果、2-アミノ-4-ベンジルオキシ-5-メトキシ安息香酸メチルが3.15g生成していた(反応収率;79.2%)。
Example 8 (Synthesis of methyl 2-amino-4-benzyloxy-5-methoxybenzoate)
In Example 6, the reaction was performed in the same manner as in Example 6 except that 3% by mass of platinum sulfide / carbon was changed to 5% by mass of rhodium / carbon. As a result, 3.15 g of methyl 2-amino-4-benzyloxy-5-methoxybenzoate was produced (reaction yield: 79.2%).

本発明は、アラルキルオキシ又はヘテロアラルキルオキシ基を有するニトロベンゼンと水素とを反応させ、脱アラルキル化又は脱ヘテロアラルキル化をさせることなく、アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンを製造する方法に関する。アラルキルオキシ又はヘテロアラルキルオキシ基を有するアニリンは、例えば、医薬・農薬等の原料や合成中間体として有用な化合物である。   The present invention relates to a method for producing an aniline having an aralkyloxy or heteroaralkyloxy group by reacting nitrobenzene having an aralkyloxy or heteroaralkyloxy group with hydrogen, without causing dearalkylation or deheteroaralkylation. Aniline having an aralkyloxy or heteroaralkyloxy group is a useful compound as a raw material for pharmaceuticals, agricultural chemicals, etc., or a synthetic intermediate.

Claims (3)

白金/炭素、硫化白金/炭素、パラジウム−白金/炭素、酸化白金、白金/アルミナ及びロジウム/炭素からなる群より選ばれる少なくとも1種の金属触媒の存在下、一般式(1)

(式中、Rは、アルコキシカルボニル基を示す。)
示されるベンジルオキシ基を有するニトロベンゼンと水素とを反応させることを特徴とする、一般式(2)

(式中、は、前記と同義である。)
示されるベンジルオキシ基を有するアニリンの製法。
In the presence of at least one metal catalyst selected from the group consisting of platinum / carbon, platinum sulfide / carbon, palladium-platinum / carbon, platinum oxide, platinum / alumina and rhodium / carbon , the general formula (1)

(In the formula, R represents an alkoxycarbonyl group .)
Characterized by reacting a nitrobenzene and hydrogen with benzyl Oki sheet group represented in the general formula (2)

(Wherein, R has the same meaning as described above.)
Preparation of the aniline with benzyl Oki sheet group shown in.
前記金属触媒が、硫化白金/炭素、白金/アルミナ及びロジウム/炭素からなる群より選ばれる少なくとも1種である請求項1記載のベンジルオキシ基を有するアニリンの製法。 Wherein the metal catalyst is, preparation of aniline with benzyl Oki sheet group according to claim 1, wherein at least one selected from the group consisting of platinum sulfide / carbon, platinum / alumina and rhodium / carbon. 前記ベンジルオキシ基を有するニトロベンゼンが、4−ベンジルオキシ−5−メトキシ−2−ニトロ安息香酸メチルである請求項1又は2記載のベンジルオキシ基を有するアニリンの製法。The method for producing an aniline having a benzyloxy group according to claim 1 or 2, wherein the nitrobenzene having a benzyloxy group is methyl 4-benzyloxy-5-methoxy-2-nitrobenzoate.
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