CN105801422A - Preparation method of o-nitrobenzol - Google Patents

Preparation method of o-nitrobenzol Download PDF

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Publication number
CN105801422A
CN105801422A CN201610229777.4A CN201610229777A CN105801422A CN 105801422 A CN105801422 A CN 105801422A CN 201610229777 A CN201610229777 A CN 201610229777A CN 105801422 A CN105801422 A CN 105801422A
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China
Prior art keywords
benzoquinone
ethane
bis
reaction
methanol
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Pending
Application number
CN201610229777.4A
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Chinese (zh)
Inventor
唐鹏飞
彭本军
白广利
彭志刚
李铭
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Jiangsu Xinhuai River Pharmtech Co ltd
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Jiangsu Xinhuai River Pharmtech Co ltd
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Priority to CN201610229777.4A priority Critical patent/CN105801422A/en
Publication of CN105801422A publication Critical patent/CN105801422A/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06Preparation of nitro compounds
    • C07C201/12Preparation of nitro compounds by reactions not involving the formation of nitro groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a preparation method of o-nitrobenzol, which takes 1, 2-bis (o-nitrophenyl) ethane (13) as a raw material to react with benzoquinone; after the reaction is finished, evaporating excessive benzoquinone and a byproduct hydroquinone; adding methanol into the residue for dissolving, and then adding sodium borohydride for reduction; after the reduction reaction, the solvent methanol is recovered, and 160-165 ℃/15mmHg target product o-nitrobenzyl alcohol is collected by distillation. The method for preparing the o-nitrobenzol by directly reacting the raw material 1, 2-bis (o-nitrophenyl) ethane with benzoquinone has a symmetrical structure, is simple, can recycle byproducts, and has great industrial value.

Description

The preparation method of nitro alcohol
Technical field
The present invention relates to a kind of pharmaceutical-chemical intermediate, be specifically related to the preparation method of a kind of nitro alcohol.
Background technology
Nitro alcohol is important organic synthesis, medicine intermediate, can synthesize treatment coronary disease through nitro alcohol Sick angina drug nifedipine and hypertension agents nifedipine etc..Main preparation methods is as follows:
1, with ortho-methylnitrobenzene as raw material, the substitution reaction first issuing raw free radical with bromine in the catalysis of peroxide prepares adjacent nitre Bromide benzyl, then hydrolysis obtains nitro alcohol in the basic conditions, its synthetic route is as follows:
Intermediate product neighbour's nitro bromobenzyl that the method first step generates has stronger corrosivity, has higher requirement to equipment, And yield is relatively low, document is reported as 70%.
2, in United States Patent (USP) US4994568 A1 and US4260627 A1, with adjacent nitrochloroformate as raw material, with 4- Dimethylamino naphthyridine reaction prepares containing crude mixture, extracts organic facies, and vacuum drying obtains nitro alcohol, and it synthesizes road Line is as follows:
3, with 1-Formyl-2-nitrobenzene as raw material, reduction reaction is occurred to obtain adjacent nitre in oxolane with boron trifluoride diethyl etherate Base benzyl alcohol, its synthetic route is as follows:
The method route is simple, and yield is high, however it is necessary that and carries out at low temperatures, and raw material is costly.
4, with benzyl phenol as raw material, dichloromethane and dinitrogen pentoxide generation oxidation reaction obtain nitro alcohol and to nitre Base benzyl alcohol, its synthetic route is as follows:
The method obtains the mixture of nitro alcohol and p nitrobenzyl alcohol, is not readily separated purification, is not suitable for industry metaplasia Produce.
5, with p nitrobenzyl alcohol as raw material, under conditions of heating, react 2h with phosphotungstic acid, prepare ortho-nitrophenyl first Alcohol, its synthetic route is as follows:
The method obtains product ultimate yield and is about 86%, but course of reaction needs heating, and energy consumption is bigger.
Summary of the invention
It is an object of the invention to: the preparation method of a kind of nitro alcohol is provided,
The raw material 1 of symmetrical structure, 2-bis-(O-Nitrophenylfluorone) ethane and benzoquinone direct reaction is utilized to prepare nitro alcohol, Method is succinct, and by-product can recycle, great industrial value.
The technical solution of the present invention is: with 1, and 2-bis-(O-Nitrophenylfluorone) ethane is raw material, reacts with benzoquinone;Reaction After end, steam benzoquinone and the by-product hydroquinone of excess;In residue, add methanol dissolve, add sodium borohydride also Former reaction;After reduction reaction, recycling design methanol, 160-165 DEG C/15mmHg target product ortho-nitrophenyl first is collected in distillation Alcohol;Its reaction equation is as follows:
It specifically comprise the following steps that 1, the benzoquinone of 2-bis-(O-Nitrophenylfluorone) ethane and its 5-10 times of mole, in 120-150 DEG C is reacted 4-8 hour;After reaction terminates, the benzoquinone of recovered under reduced pressure excess and by-product hydroquinone;In residue Adding 1, the methanol of 3 times of weight of 2-bis-(O-Nitrophenylfluorone) ethane dissolves, and adds 1, and 2-bis-(O-Nitrophenylfluorone) ethane etc. rubs 15 DEG C of reduction reactions of sodium borohydride of your amount;After reduction reaction, recycling design methanol, 160-165 DEG C/15mmHg is collected in distillation Target product nitro alcohol.
The invention have the advantage that raw material 1,2-bis-(O-Nitrophenylfluorone) ethane is raw material condensation preparation by adjacent nitro benzyl chloride, The benzoquinone of excess and by-product hydroquinone can be to be utilized respectively after recovered under reduced pressure, separation, and concise in technology, industrial value is high.
Detailed description of the invention
Further illustrate the technical solution of the present invention below in conjunction with specific embodiment, these embodiments it is not intended that It it is the restriction to technical scheme.
The analytical tool used in embodiment and equipment: gas chromatography mass spectrometry, MS5973N-GC6890N(U.S. Agilent is public Department);Nuclear magnetic resonance analyser, AVANCE DMX II I 500M(TMS internal standard, Bruker company);High performance liquid chromatograph: Agilent Technologies 1200 Series。
Embodiment 1: 136 grams of 1,2-bis-(O-Nitrophenylfluorone) ethane (0.50mol), 324 grams of benzoquinone (3.0mol) are added In four mouthfuls of reaction bulbs of 1000 milliliters, after heating and melting, stirring and react 6 hours in 135-140 DEG C, high performance liquid chromatography is followed the tracks of Detection;After reaction, the benzoquinone of water pump recovered under reduced pressure excess and by-product hydroquinone;408 grams of methanol are added molten in residue Solve, add 19 grams of sodium borohydrides (0.5 mole), in 15 DEG C of stirring reactions 2 hours;After reduction reaction, recycling design methanol, 160-165 DEG C/15mmHg product 145.4 grams is collected in distillation, for target product nitro alcohol, liquid content 94.9%, yield 90.2%;Light yellow crystal 125.2 grams, mp70~72 DEG C, liquid content 99.2%, total recovery 81.1% is obtained with re crystallization from toluene.
Product structure is verified:1H NMR (CDCl3, 500 MHz) δ (ppm): 4.97 (s, 2H),7.47 (m, 1H), 7.67 (m, 1H), 7.73−7.47(m, 1H), 8.1 (dd, J = 8.0, 1 Hz, 1H);13C NMR (CDCl3, 125MHz) δ (ppm): 62.5, 124.9, 128.48, 129.9, 134.1, 136.8。
Embodiment 2~8: the preparation condition experiment of 1-Formyl-2-nitrobenzene
136 grams of 1,2-bis-(O-Nitrophenylfluorone) ethane (0.50mol), a certain amount of benzoquinone are joined four mouthfuls of 1000 milliliters instead Answer in bottle, after heating and melting, stir and react in uniform temperature, high performance liquid chromatography tracing detection;After reaction, water pump recovered under reduced pressure The benzoquinone of excess and by-product hydroquinone;In residue, add 408 grams of methanol dissolve, add 19 grams of sodium borohydrides (0.5 Mole), in 15 DEG C of stirring reactions 2 hours;After reduction reaction, recycling design methanol, 160-165 DEG C/15mmHg is collected in distillation Product, liquid phase analysis content, calculated yield, result such as following table.

Claims (2)

1. the preparation method of nitro alcohol, is characterized in that: with 1, and 2-bis-(O-Nitrophenylfluorone) ethane is raw material, anti-with benzoquinone Should;After reaction terminates, steam benzoquinone and the by-product hydroquinone of excess;In residue, add methanol dissolve, add boron Sodium hydride reduces;After reduction reaction, recycling design methanol, 160-165 DEG C/15mmHg target product ortho-nitrophenyl is collected in distillation Methanol;Its reaction equation is as follows:
The preparation method of nitro alcohol the most according to claim 1, it is characterized in that it specifically comprises the following steps that 1, 2-bis-(O-Nitrophenylfluorone) ethane and the benzoquinone of its 5-10 times of mole, react 4-8 hour in 120-150 DEG C;After reaction terminates, The benzoquinone of recovered under reduced pressure excess and by-product hydroquinone;3 times of weights of 1,2-bis-(O-Nitrophenylfluorone) ethane are added in residue The methanol of amount dissolves, and adds 1,15 DEG C of reduction reactions of the sodium borohydride of 2-bis-(O-Nitrophenylfluorone) ethane equimolar amounts;Reduction After reaction, recycling design methanol, 160-165 DEG C/15mmHg target product nitro alcohol is collected in distillation.
CN201610229777.4A 2016-04-14 2016-04-14 Preparation method of o-nitrobenzol Pending CN105801422A (en)

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CN201610229777.4A CN105801422A (en) 2016-04-14 2016-04-14 Preparation method of o-nitrobenzol

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1819984A (en) * 2003-08-27 2006-08-16 庵原化学工业株式会社 Production of aromatic aldehyde
CN102070596A (en) * 2011-01-22 2011-05-25 浙江大学 Preparation method for dihydrosafrole
CN105152947A (en) * 2015-09-09 2015-12-16 江苏正大清江制药有限公司 Preparation method of 2-amino-3,5-dibromobenzaldehyde

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1819984A (en) * 2003-08-27 2006-08-16 庵原化学工业株式会社 Production of aromatic aldehyde
CN102070596A (en) * 2011-01-22 2011-05-25 浙江大学 Preparation method for dihydrosafrole
CN105152947A (en) * 2015-09-09 2015-12-16 江苏正大清江制药有限公司 Preparation method of 2-amino-3,5-dibromobenzaldehyde

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LIPENG ZHOU ET AL.: "Electronic Effect of Substituent of Quinones on their Catalytic Performance in Hydrocarbons Oxidation", 《CATALYSIS LETTERS》 *
QIAOHONG ZHANG ET AL.: "Efficient metal-free aerobic oxidation of aromatic hydrocarbons utilizing aryl-tetrahalogenated N-hydroxyphthalimides and 1,4-diamino-2,3-dichloroanthraquinone", 《JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY》 *

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