CN108101808A - A kind of synthetic method of oxalic acid monoalkyl ester-[(aryl) methene] hydrazide kind compound - Google Patents
A kind of synthetic method of oxalic acid monoalkyl ester-[(aryl) methene] hydrazide kind compound Download PDFInfo
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- CN108101808A CN108101808A CN201711446931.4A CN201711446931A CN108101808A CN 108101808 A CN108101808 A CN 108101808A CN 201711446931 A CN201711446931 A CN 201711446931A CN 108101808 A CN108101808 A CN 108101808A
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- oxalic acid
- acid monoalkyl
- monoalkyl ester
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/16—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of hydrazones
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Abstract
The invention discloses a kind of synthetic methods of oxalic acid monoalkyl ester [(aryl) methene] hydrazide kind compound.It includes：The first step：Oxalic acid monoalkyl ester hydrazides is obtained by the reaction in dialkyl oxalate and hydrazine hydrate；Second step：Obtained oxalic acid monoalkyl ester hydrazides is obtained by the reaction to oxalic acid monoalkyl ester [(aryl) methene] hydrazide kind compound of corresponding construction from different benzaldehyde derivatives.It is synthesized from previous using organic solvent unlike such compound, the present invention makees solvent with water, has the characteristics that green, economical；And high conversion rate, yield is high, and reaction speed is fast, and post processing is simple.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of oxalic acid monoalkyl ester-[(aryl) methene] acyl
The synthetic method of hydrazine class compound.
Background technology
Schiff bases containing-CO-NH-N=C-structure, can be with transiting state metal shape due to the particularity of its structure
It is with a wide range of applications into stable Schiff base metal complex compound.Some Schiff base metal complex compounds have in field of medicaments
There are the bioactivity such as sterilization, antitumor, antituberculosis；Also there are many applications, such as the Schiff of some heterocyclics in terms of material
Alkali shows good fluorescence, is widely used in liquid crystal material, photochromic material etc.；In addition, some Schiffs
The complex compound that alkali is formed with W metal can come into operation as catalyst.The different structure of Schiff base metal complex compound determines it
Different application values, and the diversity of ligand determines that it forms the not same-action of various complex compounds with metal, due to Schiff
Alkali metal complex is widely applied value, and people have done substantial amounts of research to the synthetic method of Schiff base ligand.
Synthesis schiff base compounds generally involve the dehydrating condensation process of carbonyl and hydrazine.Such compound is synthesized to generate
Unique water byproduct needs azeotropic water removing to be smoothed out reaction for some reactions being difficult to；In addition, schiff bases
Covalent bond is a kind of dynamics covalent bond, and PH is too low to cause decomposition product for raw material, and this kind of compound is in alkaline conditions
It can be stabilized.Traditional synthetic method is mostly using common organic solvents such as ethyl alcohol, dichloromethane, toluene as solvent
Schiff bases are made in the method for heating or room temperature reaction.As the more and more application values of schiff base compound are found, people
Also to synthesize schiff bases method constantly improve and optimizate.
Di Braccio and Mario (European Journal of Medicinal Chemistry, 43 (3), 584-
594；2008) route shown in formula 1 is reported：
The molar ratio of dialkyl oxalate and hydrazine hydrate used is 3 in the document：1, the dropping temperature of hydrazine hydrate and reaction
Temperature is all room temperature, and the method by-product is more, and the waste of raw material dialkyl oxalate is too many.Water and second are used in document after reaction
Acetoacetic ester extracts reaction solution, and product is extracted into water phase, then adds in methanol：Ether=1：Solid is precipitated in 1 solution
Product, the method yield are 29%.
The content of the invention
For overcome the deficiencies in the prior art, the object of the present invention is to provide a kind of simpler, efficient, green a variety of
The synthetic method of the oxalic acid monoalkyl ester of structure-[(aryl) methene] hydrazide kind compound.This method reaction condition is mild, production
Produce rate is high, energy conservation and environmental protection.
Technical scheme is specifically described as follows.
A kind of synthetic method of oxalic acid monoalkyl ester-[(aryl) methene] hydrazide kind compound, is as follows：
The first step：Dialkyl oxalate and hydrazine hydrate are carried out that oxalic acid monoalkyl ester hydrazides is obtained by the reactionR isWherein：Dialkyl oxalate and hydrazine hydrate molar ratio are
1.95:1~2.05:1；
Second step：By oxalic acid monoalkyl ester hydrazidesReductive amination process is carried out with Benzaldehyde derivatives,
Obtain oxalic acid monoalkyl ester-[(aryl) methene] hydrazide kind compoundAr is selected from
In any one.
In the present invention, in the first step, after dialkyl oxalate is dissolved separately in ethyl alcohol with hydrazine hydrate, then in condition of ice bath
Under, it is that be added drop-wise to molar concentration be 1~2mol/ dialkyl oxalates to 0.5~1mol/L hydrazine hydrate ethanol solutions by molar concentration
In ethanol solution.
In the present invention, in the first step, solution is collected by filtration after reaction, the etoh solvent being spin-dried in solution uses acetic acid
Ethyl ester extracts raffinate with water, and product oxalic acid monoalkyl ester hydrazides is extracted into water phase, it is anti-to be directly used in second step
It should.
In the present invention, the molar ratio of aromatic aldehyde compound and hydrazine hydrate is 7:20~9:20.
In the present invention, in second step, solvent for use is water, and between reaction temperature is 25 DEG C -60 DEG C, the reaction time is
Between 15min~6h.
It in the present invention, in second step, washs, filter after reaction, is dry to get respective objects product.
It is compared with existing technology, the beneficial effects of the present invention are：It is heated instead using organic solvent with previously reported
The method that such compound should be synthesized compares, and the present invention use water that is economic, green, being easy to get as solvent, and when reacting
Between it is short, consumption of raw materials is few, and post processing is simple, and cost is greatly saved, shortens the reaction time, improves reaction yield；Reaction
Yield can reach 94%.
Specific embodiment
Technical scheme is explained in detail with reference to example.
It accurately weighs 0.5g (0.01mol) hydrazine hydrate to be dissolved in 15ml ethyl alcohol, weighs 2.72g (0.02mol) oxalic acid diethyl
Ester is dissolved in 15ml ethyl alcohol, and the ethanol solution (1mol/L) of hydrazine hydrate is slowly dropped to the ethyl alcohol containing diethy-aceto oxalate at 0 DEG C
In (1mol/L), 10min is dripped.It is stirred overnight at room temperature.Collected by suction filtrate after reaction, rotation are evaporated the solvent of filtrate
Residue is dissolved in 20ml ethyl acetate by ethyl alcohol, is extracted four times with 40ml water, collects water phase.
Embodiment 1
Oxalic acid mono ethyl ester-【(4- diethylin -2- hydroxy phenyls) methene】The preparation of hydrazides
It weighs 4,4- diethylin salicylide 120mg (0.62mmol) and is added to 10ml oxalic acid list second with ethyl oxalyl chloride
In the aqueous solution of ester hydrazides, 60 DEG C of stirring 5h, collected by suction solid, 30ml water washing filter cakes, vacuum drains to obtain yellow solid
Powder 170mg, compared with 4,4 diethylin salicylides calculate yield be 94%.
1H NMR(501MHz,Chloroform-d)δ10.99(s,1H),10.17(s,1H),8.39(s,1H),7.11
(d, J=8.5Hz, 1H), 6.32 (d, J=10.2Hz, 2H), 4.48 (q, J=7.1Hz, 2H), 3.47 (q, J=6.9Hz, 4H),
1.49 (t, J=7.1Hz, 3H), 1.28 (t, J=7.0Hz, 6H)13C NMR(126MHz,Chloroform-d)δ160.86,
154.19,151.87,132.90,106.01,103.88,98.12,63.15,44.49,13.96,12.62.
Embodiment 2
Oxalic acid mono ethyl ester-【(2- aminomethyl phenyls) methene】The preparation of hydrazides
Accurately weigh the oxalic acid mono ethyl ester hydrazides that 110mg (0.917mmol) 4- nitro -3- hydroxy benzaldehydes are added to 10ml
Aqueous solution in, stir 70min under room temperature, collected by suction solid, vacuum is drained, and is obtained with 30ml water washings solid three times
To white powder solid 150mg, compared with 4- nitro -3- hydroxy benzaldehydes calculate yield is 76.9%.
1H NMR(501MHz,Chloroform-d)δ10.41(s,1H),8.68(s,1H),7.96(s,1H),7.29(d,
J=8.2Hz, 1H), 7.22-7.15 (m, 2H), 4.39 (q, J=7.1Hz, 2H), 2.46 (s, 3H), 1.39 (t, J=7.1Hz,
3H).13C NMR(126MHz,Chloroform-d)δ160.37,152.63,150.34,137.76,131.08,130.93,
130.84,127.31,126.36,63.55,19.40,13.97.
Embodiment 3
Oxalic acid mono ethyl ester-【(3,4,5- trimethoxyphenyls) methene】The preparation of hydrazides
Accurately weigh 100mg (0.5mmol) 3,4,5-Trimethoxybenzaldehydes and 67mg (0.5mmol) ethyl oxalyl chloride
It is added in 10ml water, stirs 15min under room temperature, filter, filter cake is washed with water several times, vacuum is drained, and it is solid to obtain white
Body 158mg, compared with 3,4,5-Trimethoxybenzaldehyde calculate yield be 73.3%.
1H NMR(501MHz,Chloroform-d)δ10.82(s,1H),8.39(s,1H),7.03(s,2H),4.44(q,
J=7.1Hz, 2H), 3.93 (d, J=6.4Hz, 9H), 1.45 (t, J=7.1Hz, 3H)13C NMR(126MHz,
Chloroform-d)δ160.19,153.43,151.80,140.66,105.15,63.55,60.92,56.26,13.93。
Claims (6)
- A kind of 1. synthetic method of oxalic acid monoalkyl ester-[(aryl) methene] hydrazide kind compound, which is characterized in that specific step It is rapid as follows：The first step：Dialkyl oxalate and hydrazine hydrate are carried out that oxalic acid monoalkyl ester hydrazides is obtained by the reactionR isWherein：Dialkyl oxalate and hydrazine hydrate molar ratio are 1.95:1~2.05:1；Second step：By oxalic acid monoalkyl ester hydrazidesReductive amination process is carried out with Benzaldehyde derivatives, is obtained Oxalic acid monoalkyl ester-[(aryl) methene] hydrazide kind compoundAr is selected fromIn any one.
- 2. synthetic method according to claim 1, which is characterized in that in the first step, dialkyl oxalate and hydrazine hydrate point After not being dissolved in ethyl alcohol, then under condition of ice bath, molar concentration is added drop-wise to mole for 0.5~1mol/L hydrazine hydrate ethanol solutions Concentration is in 1~2mol/ dialkyl oxalate ethanol solutions.
- 3. synthetic method according to claim 2, which is characterized in that in the first step, solution is collected by filtration after reaction, The etoh solvent being spin-dried in solution extracts raffinate with water with ethyl acetate, and product oxalic acid monoalkyl ester hydrazides is extracted It gets in water phase, is directly used in second step reaction.
- 4. synthetic method according to claim 1, which is characterized in that the molar ratio of aromatic aldehyde compound and hydrazine hydrate is 7:20~9:20.
- 5. synthetic method according to claim 1, which is characterized in that in second step, solvent for use is water, and reaction temperature exists 25 DEG C -60 DEG C, the reaction time is between 15min~6h.
- 6. synthetic method according to claim 1, which is characterized in that in second step, wash, filter after reaction, is dry It is dry to get respective objects product.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109574870A (en) * | 2018-12-25 | 2019-04-05 | 维思普新材料（苏州）有限公司 | A kind of continuous preparation method of hydrazides |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109574870A (en) * | 2018-12-25 | 2019-04-05 | 维思普新材料（苏州）有限公司 | A kind of continuous preparation method of hydrazides |
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Application publication date: 20180601 |