CN110452133A - A kind of preparation method of diazanyl phthalic acid methyl ester derivative - Google Patents
A kind of preparation method of diazanyl phthalic acid methyl ester derivative Download PDFInfo
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- CN110452133A CN110452133A CN201910730298.4A CN201910730298A CN110452133A CN 110452133 A CN110452133 A CN 110452133A CN 201910730298 A CN201910730298 A CN 201910730298A CN 110452133 A CN110452133 A CN 110452133A
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- methyl ester
- phthalic acid
- acid methyl
- diazanyl
- hydrazine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C241/02—Preparation of hydrazines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C241/04—Preparation of hydrazides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/28—Nitrogen atoms
- C07D295/30—Nitrogen atoms non-acylated
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- Organic Chemistry (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The present invention relates to fragrant hydrazine preparation technical fields, and in particular to a kind of preparation method of diazanyl phthalic acid methyl ester derivative includes the following steps: that (1) dissolves 4,6- dinitro -1,3- phthalic acid methyl ester；(2) hydrazine or hydrazine derivative is added to prepare 4- nitro -6- diazanyl -1,3- phthalic acid methyl ester；(3) replace nitroso reaction, phthalic acid methyl ester derivative is made；The present invention directly synthesizes fragrant hydrazine by the way of replacing, and improves reaction yield, shortens reaction step, simplifies operation, and realize and react at room temperature, reduces the energy consumption and cost of reaction.
Description
Technical field
The present invention relates to fragrant hydrazine preparation technical fields, and in particular to a kind of preparation side of diazanyl phthalic acid methyl ester derivative
Method.
Background technique
Aryl hydrazine compound is a kind of very important organic synthesis intermediate, can synthesize aromatic heterocycle, by purification, is obtained
To a series of high-efficient low toxicity insecticides, foaming agent, novel specific medicament etc. is widely applied and the fields such as pharmaceutical chemistry, chemical industry.
Therefore, there is highly important theory significance and application value to the research and development of fragrant hydrazine and its derivative.
Mainly passing through primary amine generates diazonium salt through diazo-reaction for the synthesis of virtue hydrazine at present, then is reserved nitrogen reaction, raw
Obtained fragrant hydrazine is reacted at fragrant hydrazine and through Fischer virtue hydrazine.Both route of synthesis are all aryl primary amines through diazo-reaction, are generated
The problems such as diazonium salt, then prepare fragrant hydrazine through reduction, many and diverse, complicated for operation, reduction that there are reaction steps is not exclusively, conversion ratio is low,
As explicitly pointed out in document " synthesising process research of smooth class pharmaceutical intermediate hydrazinobenzene hydrochloride salt " " to such in many patent documents
The synthesis of compound by after corresponding nitrobenzene reduction, diazotising, SnCl2Three steps are restored to obtain.This method is gone back because nitro
Original uses hydrogen, and there are security risks, and the arylamine after reduction is unstable；Diazotising needs to complete under low temperature, reaction condition requirement
It is harsh；Diazonium salt is unstable, and there are security risks for easy decomposition generation nitrogen.The above reaction system is complicated, cumbersome, easily
Lead to problems such as total recovery low, and in document Schoutissen, H.A.J.Rec.Trav.Chim.1935,54,253-255.,
Samsoniya,S.A.；Targamadze,N.L.；Tretyakova,L.G.；Efimova,T.K.；Turchin,K.F.；
Gverdtsiteli,I.M.；Suvorov, N.N.Chem.Heterocycl.Comp.1977,13,757-763. and Rajca,
A.；Olankitwanit,A.；Rajca, S., | on the basis of J.Am.Chem.Soc.2011,133,4750-4753 is disclosed also simultaneously
The yield aspects of two diazanyl benzene make further investigation between not being directed to.
Although patent No. CN200610161376.6, which is disclosed, synthesizes two fragrant hydrazines and diphenyl amine by aromatic nitro compound
Method, by co-catalyst Isosorbide-5-Nitrae-how the synergistic effect of quinone or 1,4-naphthoquinone derivative and Pd/C catalyst, but this method is difficult
To control the technological parameter in reaction process, specific requirement are as follows: in the 30%-50% alkali made of sodium hydroxide or potassium hydroxide
Property solution in, be added the emulsifier of alkyl benzene sulfonate, co-catalyst Isosorbide-5-Nitrae-how quinone or 1,4-naphthoquinone derivative and Pd/C, virtue
Aromatic nitro compounds；50-100 DEG C of heating, is kept stirring speed 300r/min or so；Be passed through hydrogen, keep pressure 0.05~
0.5Mpa；When hydrogen does not reabsorb, reaction end is reached；It filters while hot, and elutes solid with water；It is diluted with water filtrate, it is cold
But to 10-15 DEG C, 6-8 hours is kept the temperature and is filtered, collect solid, drying；Crude product is recrystallized with alcohol.It is related to hydrogen in this method to lead
There are security risks in cause production.
So this field urgently it is expected that developing the mode that a safe, easy to operate, step of synthesis is simple and efficient synthesizes virtue
Hydrazine.
Summary of the invention
The present invention is in order to solve the above technical problems, provide a kind of preparation method of diazanyl phthalic acid methyl ester derivative.
It is realized particular by following technical scheme:
A kind of preparation method of diazanyl phthalic acid methyl ester derivative includes the following steps: that (1) dissolves 4,6- dinitro-
1,3- phthalic acid methyl ester；(2) hydrazine or hydrazine derivative is added to prepare 4- nitro -6- diazanyl -1,3- phthalic acid methyl ester；(3) it takes
For nitroso reaction, phthalic acid methyl ester derivative is made.
Further, the preparation method of diazanyl phthalic acid methyl ester derivative, specifically comprises the following steps:
(1) 4,6- dinitro -1,3- phthalic acid methyl ester is dissolved in solvent, is stirred at room temperature；
(2) hydrazine or hydrazine derivative are added into solution, after stirring, obtains 4- nitro -6- diazanyl -1,3- phthalic acid first
Ester；
(3) continue after stirring 2-10h, add water, be extracted with ethyl acetate, be concentrated, to get benzene after recrystallization or column chromatography
Dicarboxylic acid methyl ester derivative.
The solvent is tetrahydrofuran, acetonitrile, methanol, ethyl alcohol, any one in DMF, DMA or DMSO.
The hydrazine derivative be hydrazine hydrate, phenylhydrazine, heteroaromatic hydrazine, alkyl hydrazine, heterocycle hydrazine, any one in acid hydrazide or
It is several.
Recrystallization solvent used is water, ethyl acetate, petroleum ether, ether, tetrahydrofuran, methanol, any one in ethyl alcohol
Kind is several.
The phthalic acid methyl ester derivative be bis- diazanyl -1,3- phthalic acid methyl ester of 4,6-, diazanyl -1 4- nitro -6-,
Any one in 3- phthalic acid methyl ester or two kinds of mixture.
Compared with prior art, the beneficial effect of the invention is:
With the method for conventional synthesis phenylhydrazine (reduction of nitro, diazotising and diazonium salt reduction step, totally three step) compare
Compared with, the present invention by the way of replacing can direct one-step synthesis virtue hydrazine, shorten reaction step, simplify operation, improve reaction
Yield, and realize and react at room temperature, reduce the energy consumption output and cost input of reaction.
The present invention is compared with existing synthesis hydrazine class compound method, with synthesis step is few, is easy to operate and control, spreads out
The features such as two packing spaces, yield are high, at low cost.
Specific embodiment
Specific embodiments of the present invention will be described in further detail below, but the invention is not limited to these realities
Mode is applied, it is claimed to still fall within the claims in the present invention for any improvement or replacement on the present embodiment essence spirit
Range.
Embodiment 1
Present embodiments provide the synthetic method of 4,6-, bis- diazanyl -1,3- phthalic acid methyl ester derivative, concrete operations are as follows:
4,6- dinitro -1,3- the phthalic acid methyl ester and tetrahydrofuran of 2.50g, 8.79mmol is added in there-necked flask in 100mL
20mL, is stirred at room temperature down, and the hydrazine hydrate of 10mL, purity 80% is added, and continues to stir 8h, and thin-layered chromatography detects fully reacting,
Reaction solution, which is poured into 100mL water, solid precipitation, filters, and washing obtains the faint yellow solid 4 of 1.85g, bis- diazanyl of 6--
1,3- phthalic acid methyl ester.
The yield of the present embodiment is 83%；
The effect of nuclear magnetic resonance shows as follows: δ=9.00 (s, 2H) 1H NMR (CDCl3,400MHz), 8.52 (s, 1H),
6.90(s,1H),3.83(s,6H),3.67(s,4H)。
The present embodiment is that synthetic route is as follows:
Embodiment 2
Present embodiments provide the synthetic method of 4,6-, bis- diazanyl -1,3- phthalic acid methyl ester derivative, concrete operations are as follows:
4,6- dinitro -1,3- the phthalic acid methyl ester and tetrahydrofuran of 2.50g, 8.79mmol is added in there-necked flask in 100mL
20mL, is stirred at room temperature down, and the N- amino-morpholine of 2.24g, 22mmol is added, and continues to stir 6h, thin-layered chromatography detection has been reacted
Entirely, reaction solution is poured into 100mL water, ethyl acetate extraction, column chromatography for separation obtains the faint yellow solid 4,6- of 2.53g
Two diazanyl -1,3- phthalic acid methyl ester derivatives；
The yield 73% of the present embodiment.
The present embodiment is that synthetic route is as follows:
Embodiment 3
Present embodiments provide the synthetic method of 4,6-, bis- diazanyl -1,3- phthalic acid methyl ester derivative, concrete operations are as follows:
4,6- dinitro -1,3- the phthalic acid methyl ester and tetrahydrofuran of 2.50g, 8.79mmol is added in there-necked flask in 100mL
20mL, is stirred at room temperature down, and 2.38g, 22mmol phenylhydrazine is added, and continues stirring for 24 hours, and thin-layered chromatography detects fully reacting, will be anti-
Liquid is answered to be poured into 100mL water, ethyl acetate extraction, column chromatography for separation obtains the faint yellow solid 4 of 161g, bis- diazanyl -1 6-,
3- phthalic acid methyl ester derivative；
The yield of the present embodiment is 45%.
The present embodiment is that synthetic route is as follows:
Embodiment 4
Present embodiments provide the synthetic method of 4- nitro -6- diazanyl -1,3- phthalic acid methyl ester derivative, concrete operations
Are as follows: the 4,6- dinitro -1,3- phthalic acid methyl ester and tetrahydrofuran of 2.50g, 8.79mmol is added in there-necked flask in 100mL
20mL, is stirred at room temperature down, and the tertbutyloxycarbonyl hydrazine of 1.16g, 8.79mmol is added, and continues to stir 1h, thin-layered chromatography detection is anti-
It answers, reaction solution is poured into water, ethyl acetate extraction, column chromatography for separation obtains yellow solid 4- nitro -6- diazanyl -1,3- benzene
Dicarboxylic acid methyl ester；
The yield of the present embodiment is 30%；
The effect of nuclear magnetic resonance shows as follows: δ=9.50 (s, 1H) 1H NMR (CDCl3,400MHz), 8.53 (s, 1H),
7.26(s,1H),6.43(s,1H),3.94(s,3H),3.87(s,3H),1.45(s,9H)。
The present embodiment is that synthetic route is as follows:
Embodiment 5
Present embodiments provide the synthetic method of 4- nitro -6- diazanyl -1,3- phthalic acid methyl ester derivative, concrete operations
Are as follows: the 4,6- dinitro -1,3- phthalic acid methyl ester and tetrahydrofuran of 2.50g, 8.79mmol is added in there-necked flask in 100mL
20mL, is stirred at room temperature down, and the benzoyl hydrazine of 1.20g, 8.79mmol is added, and continues to stir 1h, thin-layered chromatography detection reaction will
Reaction solution is poured into water, and ethyl acetate extraction, column chromatography for separation obtains yellow solid 4- nitro -6- diazanyl -1,3- benzene diformazan
Sour methyl esters；
The yield 30% of the present embodiment；
The effect of nuclear magnetic resonance shows as follows: δ=9.71 (s, 1H) 1H NMR (CDCl3,400MHz), 8.45 (s, 1H),
8.32(s,1H),7.85(d,2H),7.57(t,1H),7.46(t,2H),7.13(s,1H),3.93(s,3H),3.85(s,3H)。
The present embodiment is that synthetic route is as follows:
Claims (6)
1. a kind of preparation method of diazanyl phthalic acid methyl ester derivative, which comprises the steps of: (1) 4 are dissolved,
6- dinitro -1,3- phthalic acid methyl ester；(2) hydrazine or hydrazine derivative is added to prepare 4- nitro -6- diazanyl -1,3- phthalic acid first
Ester；(3) replace nitroso reaction, phthalic acid methyl ester derivative is made.
2. the preparation method of diazanyl phthalic acid methyl ester derivative as described in claim 1, which is characterized in that diazanyl phthalic acid
The preparation method of methyl ester derivation, specifically comprises the following steps:
(1) 4,6- dinitro -1,3- phthalic acid methyl ester is dissolved in solvent, is stirred at room temperature；
(2) hydrazine or hydrazine derivative are added into solution, after stirring, obtains 4- nitro -6- diazanyl -1,3- phthalic acid methyl ester；
(3) continue after stirring 2-10h, add water, be extracted with ethyl acetate, be concentrated, to get benzene diformazan after recrystallization or column chromatography
Sour methyl ester derivation.
3. the preparation method of diazanyl phthalic acid methyl ester derivative as described in claim 1, which is characterized in that the solvent is four
Hydrogen furans, acetonitrile, methanol, ethyl alcohol, any one in DMF, DMA or DMSO.
4. the preparation method of diazanyl phthalic acid methyl ester derivative as described in claim 1, which is characterized in that the hydrazine is derivative
Object is hydrazine hydrate, phenylhydrazine, heteroaromatic hydrazine, alkyl hydrazine, heterocycle hydrazine, any one or a few in acid hydrazide.
5. the preparation method of diazanyl phthalic acid methyl ester derivative as described in claim 1, which is characterized in that recrystallization used is molten
Agent is water, ethyl acetate, petroleum ether, ether, tetrahydrofuran, methanol, any one or a few in ethyl alcohol.
6. the preparation method of diazanyl phthalic acid methyl ester derivative as described in claim 1, which is characterized in that the phthalic acid
Methyl ester derivation is bis- diazanyl -1,3- phthalic acid methyl ester of 4,6-, any in 4- nitro -6- diazanyl -1,3- phthalic acid methyl ester
One or two kinds of mixtures.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB594453A (en) * | 1943-02-10 | 1947-11-12 | Henry Dreyfus | Improvements in or relating to organic derivatives of hydrazine |
| GB629177A (en) * | 1945-12-21 | 1949-09-14 | Ciba Ltd | Manufacture of new hydrazine compounds and derivatives thereof |
-
2019
- 2019-08-08 CN CN201910730298.4A patent/CN110452133A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB594453A (en) * | 1943-02-10 | 1947-11-12 | Henry Dreyfus | Improvements in or relating to organic derivatives of hydrazine |
| GB629177A (en) * | 1945-12-21 | 1949-09-14 | Ciba Ltd | Manufacture of new hydrazine compounds and derivatives thereof |
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Application publication date: 20191115 |