CN109574870A - A kind of continuous preparation method of hydrazides - Google Patents
A kind of continuous preparation method of hydrazides Download PDFInfo
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- CN109574870A CN109574870A CN201811592618.6A CN201811592618A CN109574870A CN 109574870 A CN109574870 A CN 109574870A CN 201811592618 A CN201811592618 A CN 201811592618A CN 109574870 A CN109574870 A CN 109574870A
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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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/86—Hydrazides; Thio or imino analogues thereof
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Abstract
The present invention relates to a kind of continuous preparation methods of hydrazides.The preparation method includes: to make ester, acid anhydrides or acyl chlorides under solvent-free in micro passage reaction or pipeline reactor or the solution successive reaction with hydrazine or hydrazine prepares hydrazide kind compound in a solvent.Preparation method of the invention is simple, and process flow is short, and the three wastes are few, is conducive to protect environment, is suitble to industrialized production；The reactor reaction time that the present invention uses is short, highly-safe, it can be achieved that continuous production；Space utilization rate of the reactor that the present invention uses in workshop is high, it can be achieved that large-scale production；Using preparation method of the invention, solvent can recycle use, reduce production cost；Using preparation method of the invention, feed stock conversion is high, stay in grade, purity is high.
Description
Technical field
The present invention relates to a kind of continuous preparation methods of hydrazides, belong to chemical synthesis and industrial production technology field.
Background technique
In the 21st century, chemical process develops towards more green, safe and efficient direction, and new process, new equipment,
The exploitation of new technology is highly important for the progress of chemical process.In this context, micro- chemical system is inhaled
The very big concern of researcher and the producer are drawn.Micro- chemical system is not simple microminiature chemical system, and is referred to micro-
The novel chemical system of reaction or micro- separative unit.In micro- chemical system, microreactor is important one of core.
Pipeline reactor (or micro passage reaction) is the important kind of microreactor, and inside is comprising of various shapes micro- logical
Corresponding reaction occurs when reactant passes through microchannel for road.Since its internal micro-structure has microreactor equipment
Great specific surface area, up to even thousands of times of hundred times of stirred tank specific surface area.Microreactor have fabulous heat transfer and
Mass transfer ability, the moment that material may be implemented uniformly mixes and efficient heat transfer, therefore many can not be real in conventional reactor
The reaction that existing reaction can be realized in microreactor or conversion ratio is low can realize high conversion in microreactor
Rate.Meanwhile it is can wrap in microreactor containing millions of minitype channel, therefore also realize very high yield (every
Year flux kiloton or more may be implemented in microreactor).
Hydrazides, which refers to, contains-CONHNR3R4The general name of the compound of group a kind of in this way, they are widely used in pesticide, doctor
Medicine, dyestuff, in functional material.Report about their synthesis is more, usually with ester, acid anhydrides or acyl chlorides and corresponding hydrazine into
Row reaction obtains, this has many descriptions in some Chinese and foreign documents.
Such as: Chemische Berichte, 1894,27,2685；Chemische Berichte, 1924,57,1324；
Inorg.Synth., 1953,4,32；Chemical and Pharmaceutical Bulletin, 1970,18,217-218；
Synthetic Communications, 2006,36 (18), 2613~2619；US 3258485；US 4496761；DE
2112398；West China pharmaceutical journal, 1997,12 (4), 240-242；Modern, 2003,2 (2), 12~14；Fine petroleum
Work, 2004,4,44~48；Chemistry notification, 2006,9,668~673；Synthesis chemistry, 2011,19 (6), 775~77；The material containing energy
Material, 2016,24 (12), 1151~1155；Chemical Engineer, 2001,4,7~8；CN 106117079A；CN102558001A this
Kind occur the problem that (1) can be led because of violent exothermic reaction using the method that hybrid reaction is added dropwise in process of production
Cause the presence of the hidden dangers such as slug.(2) it will appear how acylated or acylated insufficient by-product；It is for some reaction products
The reaction of solid leads to the increase of by-product list hydrazides since the problem of wrapping up is in the case of bishydrazide reacts insufficient；By
In the mass transfer the problem of, the increase of mostly acylated by-product will lead to for the compound of single hydrazides.(3) it will lead to the increasing of the three wastes
Add.Since by-product increases in reaction process, quantity of three wastes can be further increased.There are also document and patent reports using acid and
The hydrazine method that reaction prepares hydrazides under conditions of catalyst, such as: CN108299228A；CN 108250100A；CN
108299230A；CN108456150A；CN 108440334A；Such method uses catalyst, and catalyst is generally anti-
The 10~20% of object are answered, the use of this large amount of catalyst will lead to the increase of the three wastes, with the green chemical industry requirement advocated at present
It runs counter to.
Can be efficiently solved using pipeline reactor (or micro passage reaction) occur in hydrazides preparation process it is above-mentioned
Problem.
Summary of the invention
Problems to be solved by the invention
The shortcomings that in order to overcome the above method, the present invention provides a kind of continuous preparation methods of hydrazide kind compound, wherein
The above problem occurred in hydrazides preparation process can be efficiently solved using pipeline reactor (or micro passage reaction).
The solution to the problem
The present invention provides a kind of continuous preparation method of hydrazides, wherein in micro passage reaction or pipeline reactor, makes
The solution successive reaction with hydrazine or hydrazine prepares hydrazide kind compound under solvent-free or in a solvent for ester, acid anhydrides or acyl chlorides.
Continuous preparation method according to the present invention, wherein the structure of the hydrazide kind compound is as follows,
Wherein, R1~R4For hydrogen atom or the saturated or unsaturated alkenyl group containing 1~18 carbon atom, cycloalkyl group,
Aryl radical, heteroaryl alkyl or heteroalicyclyl, optionally containing one or more halogen atoms, nitro, carboxylic acid on these groups
Base, aldehyde radical, sulfonic group or amino.
Continuous preparation method according to the present invention, wherein the solvent is selected from water, alcohols solvent, hydrocarbon solvent, halogen
For hydrocarbon solvent, ketones solvent, nitrile solvents, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide.
Continuous preparation method according to the present invention, wherein the ester, acid anhydrides or acyl chlorides and the equivalent proportion of the hydrazine are
Between 1:1.0~3.0, preferably between 1:1.0~1.5.
Continuous preparation method according to the present invention, wherein the ester, acid anhydrides or acyl chlorides are solvent-free or molar concentration
For 0.01mol/L~5mol/L, preferably 0.1mol/L~3mol/L；The hydrazine is solvent-free or molar concentration is 0.01mol/L
~5mol/L, preferably 0.1mol/L~3mol/L.
Continuous preparation method according to the present invention, wherein the inside of the micro passage reaction or pipeline reactor
Minimum spacing at the smallest cross-sectional of channel is not less than 1mm；Maximum at the inner passage maximum cross-section of the micro passage reaction
Spacing is no more than 50mm.
Continuous preparation method according to the present invention, wherein the reaction of the micro passage reaction or pipeline reactor
Pressure is between 1 bar~20 bars, preferably between 1 bar~10 bars.
Continuous preparation method according to the present invention, wherein the reaction of the micro passage reaction or pipeline reactor
Temperature is between 10~250 DEG C, preferably between 50~150 DEG C.
Continuous preparation method according to the present invention, wherein the solution of the ester, acid anhydrides or acyl chlorides and the hydrazine or hydrazine
Residence time in micro passage reaction or pipeline reactor is 1~300s, preferably 1~90s.
Continuous preparation method according to the present invention, wherein the structure of the micro passage reaction or pipeline reactor
Including cardioid, rectangle, trapezoidal, double trapezoid and irregular shape.
The effect of invention
A kind of continuous preparation method of hydrazides provided by the invention has the advantages that
Preparation method of the invention is simple, and process flow is short, and the three wastes are few, is conducive to protect environment, is suitble to industrialized production；
The reactor reaction time that the present invention uses is short, highly-safe, it can be achieved that continuous production；The reactor that the present invention uses is in vehicle
Between space utilization rate it is high, it can be achieved that large-scale production；Using preparation method of the invention, solvent can recycle use, reduce
Production cost；Using preparation method of the invention, feed stock conversion is high, stay in grade, purity is high.
Detailed description of the invention
Fig. 1 is the process flow chart of preparation method of the invention.
Fig. 2 is the schematic diagram of cardioid micro passage reaction or pipeline reactor.
Fig. 3 is the overall structure diagram of micro passage reaction or pipeline reactor.
Fig. 4 is the schematic diagram of internal structure of micro passage reaction or pipeline reactor.
Specific embodiment
The present invention provides a kind of continuous preparation method of hydrazides, wherein in micro passage reaction or pipeline reactor, makes
The solution successive reaction with hydrazine or hydrazine prepares hydrazide kind compound under solvent-free or in a solvent for ester, acid anhydrides or acyl chlorides.
The structure of the hydrazide kind compound is as follows,
Wherein, R1~R4For hydrogen atom or the saturated or unsaturated alkenyl group containing 1~18 carbon atom, cycloalkyl group,
Aryl radical, heteroaryl alkyl or heteroalicyclyl, optionally containing one or more halogen atoms, nitro, carboxylic acid on these groups
Base, aldehyde radical, sulfonic group or amino.
As containing 1~18 carbon atom saturated or unsaturated alkenyl group concrete example, can enumerate such as methyl,
Ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, tert-butyl, n-pentyl, 1- methyl normal-butyl, the positive fourth of 2- methyl
Base, 3- methyl normal-butyl, 1,1- dimethyl n propyl, n-hexyl, 1- methyl n-amyl, 2- methyl n-amyl, 1,1- dimethyl
Normal-butyl, 1- ethyl normal-butyl, 1,1,2- trimethyl n-propyl, n-heptyl, n-octyl, n-nonyl, positive decyl, undecyl,
Dodecyl, tridecyl, myristyl, pentadecyl, cetyl, heptadecyl, octadecyl and their same point
Isomers etc.；Vinyl, acrylic, allyl, cyclobutenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decene
Base, undecenyl, dodecenyl succinic, tridecylene base, tetradecene base, pentadecane alkenyl, hexadecene base, heptadecene
Base, octadecene base and their isomer etc..
As the concrete example of the cycloalkyl group containing 1~18 carbon atom, such as cyclopropyl, cyclopenta, hexamethylene can be enumerated
Base, suberyl, cyclooctyl, cyclodecyl and their isomer etc..
As the concrete example of the aryl radical containing 1~18 carbon atom, such as phenyl, tolyl, adjacent diformazan can be enumerated
Phenyl, meta-xylene base, paraxylene base, ethylbenzene, n-proplbenzene base, cumenyl, xenyl, naphthalene, anthryl, phenanthryl, pyrene
Base etc..
As the concrete example of the heteroaryl alkyl containing 1~18 carbon atom, such as furyl, thienyl, pyrroles can be enumerated
Base, thiazolyl, imidazole radicals, pyridyl group, pyrazinyl, pyrimidine radicals, pyridazinyl, indyl, quinolyl, pteridyl, acridinyl etc..
As the concrete example of the heteroalicyclyl containing 1~18 carbon atom, such as Oxyranyle, ethylene imine can be enumerated
Base, propiolactone base, butyrolactone base, caprolactam base etc..
As the concrete example of halogen, fluorine, chlorine, bromine, iodine can be enumerated.
As the concrete example of hydrazides, such as carbohydrazide, daminozide, adipic dihydrazide, dibenzoyl hydrazine, wine can be enumerated
Stone acid dihydrazide, sebacic dihydrazide, phthalylhydrazine, two hydrazine of oxalyl, salicylyl hydrazine, acethydrazide, isoniazid etc..
There is no limit can select the concrete example of the ester, acid anhydrides or acyl chlorides according to hydrazides to be prepared.
The solvent is not particularly limited, and is preferably chosen from water, alcohols solvent, hydrocarbon solvent, halogenated hydrocarbon solvent, ketone
Solvent, nitrile solvents, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide.
As the concrete example of alcohols solvent, such as methanol, ethyl alcohol, propyl alcohol, butanol, cyclohexanol, Lotka-Volterra circle system, the last of the ten Heavenly stems can be enumerated
Alcohol etc..As the concrete example of hydrocarbon solvent, such as methane, ethane, propane, butane, pentane, hexane, heptane, pungent can be enumerated
Alkane, nonane, decane etc..As the concrete example of halogenated hydrocarbon solvent, such as chloromethanes, chloroethanes, chloropropane, neoprene can be enumerated
Alkane, bromomethane, bromoethane, N-Propyl Bromide, bromobutane etc..As the concrete example of ketones solvent, such as methyl ethyl ketone, third can be enumerated
Ketone, butanone, pentanone, propiophenone etc..As the concrete example of nitrile solvents, such as formonitrile HCN, acetonitrile, acrylonitrile, valeronitrile can be enumerated
Deng.
The equivalent proportion of the ester, acid anhydrides or acyl chlorides and the hydrazine is between 1:1.0~3.0, preferably between 1:1.0~1.5.
When the equivalent of the hydrazine is very few, it is incomplete to will cause ester, acid anhydrides or acyl chloride reaction, reduces yield and product purity；When described
When the equivalent of hydrazine is excessive, although conversion ratio is higher, increased costs, while the remaining more unreacted hydrazine of meeting in product, it reduces
Product purity.
The ester, acid anhydrides or acyl chlorides are solvent-free or molar concentration is 0.01mol/L~5mol/L, preferably 0.1mol/L~
3mol/L；The hydrazine is solvent-free or molar concentration is 0.01mol/L~5mol/L, preferably 0.1mol/L~3mol/L.When upper
State substance molar concentration it is too low when, reaction speed is slack-off, and the residence time is caused to increase；When the molar concentration of above-mentioned substance is excessively high
When, the solid particle that unit time interior reaction is formed is excessive, be easy to cause channel blockage.
Minimum spacing at the inner passage smallest cross-sectional of the micro passage reaction or pipeline reactor is not less than 1mm；
Maximum spacing at the inner passage maximum cross-section of the micro passage reaction or pipeline reactor is no more than 50mm；Channel cross-section
Spacing is too small, if there is solid generation in reaction process, be easy to cause channel blockage；Channel cross-section spacing is excessive, and mixed effect subtracts
It is weak, reduce mass transfer ability.
The micro passage reaction or pipeline reactor can be commercially available from market, for example, Corning Incorporated G1,
G2, G3 and G4 micro passage reaction or pipeline reactor.
In the present invention, very high conversion ratio can be realized by using micro passage reaction or pipeline reactor.It is micro-
The number of channel reactor or pipeline reactor is not particularly limited, preferably 1~5, more preferably 1~3.Use 2
When the above micro passage reaction or pipeline reactor, each micro passage reaction or pipeline reactor arranged in series, reaction raw materials
Sequentially enter each reactor.
The structure of micro passage reaction or pipeline reactor includes rectangle, trapezoidal, double trapezoid and irregular shape, but not
It is confined to this.For example, reactor can be cardioid, as shown in Figure 2.
In the reaction, the micro passage reaction or pipeline reactor can according to need and serve as different modules, example
Such as mix warm-up block, reaction module, refrigerating module.These modules are only differentiations functionally, and geometry can be identical.
The reaction pressure of the micro passage reaction or pipeline reactor is between 1 bar~20 bars, preferably at 1 bar~10 bars
Between；Reaction temperature is between 10~250 DEG C, preferably between 50~150 DEG C；The ester, acid anhydrides or acyl chlorides and the hydrazine or
Residence time of the solution of hydrazine in micro passage reaction is 1s~300s, preferably 1s~90s, in such reaction pressure and
Under the conditions of reaction temperature, the conversion ratio of ester, acid anhydrides or acyl chlorides is up to 90% or more.
Embodiment is provided below and comparative example further illustrates preparation method of the invention.
In embodiment, micro passage reaction or pipeline reactor are commercially available from Corning Incorporated, model G1.
In embodiment and comparative example, ester, acid anhydrides, acyl chlorides, the hydrazine used can be commercially available.
Embodiment 1
The preparation of carbohydrazide
Dimethyl carbonate is dissolved in methanol, the solution of 3mol/L is made, is infused with the flow of 30ml/min by metering pump
Enter in micro passage reaction or pipeline reactor.The hydrazine hydrate aqueous solution of 80 mass % is by another metering pump with 11.26ml/
In the flow velocity injection micro passage reaction or pipeline reactor of min, is reacted 3 seconds at 75 DEG C, flow out micro passage reaction or pipe
Road reactor collects reaction mass, obtains white crystalline product, yield 99%, content 99.9%, single hydrazine content 0.01%.
Embodiment 2
The preparation of daminozide
Succinic anhydride is dissolved in methanol, the solution for standby of 2.5mol/L is made, unsymmetric dimethyl hydrazine is dissolved in methanol, is made
At the solution for standby of 2mol/L.The methanol solution of succinic anhydride is injected into microchannel plate by metering pump with the flow of 50ml/min
It answers in device or pipeline reactor, the methanol solution of unsymmetric dimethyl hydrazine is infused by another metering pump with the flow velocity of 63.2ml/min
Enter in micro passage reaction or pipeline reactor, reacted 2.5 seconds at 80 DEG C, flows out micro passage reaction or pipeline reactor,
Reaction mass is collected, white crystalline product, yield 99.5%, content 99.9%, double hydrazine contents 0.015% are obtained.Reaction is female
Liquid methanol is applied after filtering.
Embodiment 3
The preparation of adipic dihydrazide
Dimethyl adipate is dissolved in methanol, the solution for standby of 1.5mol/L is made, the hydrazine hydrate of 80 mass % is molten
In methanol, the solution for standby of 3mol/L is made.In terms of the methanol solution of dimethyl adipate is passed through by the flow of 50ml/min
Amount pump injection micro passage reaction or pipeline reactor in, by the methanol solution of hydrazine hydrate by another metering pump with
It in the flow velocity injection micro passage reaction or pipeline reactor of 63.1ml/min, is reacted 2 seconds at 80 DEG C, outflow microchannel plate is answered
Device or pipeline reactor collect reaction mass, obtain white crystalline product, content 99.9%, single hydrazine content 0.01%.Reaction
Mother liquor methanol is applied after filtering.
Embodiment 4
The preparation of dibenzoyl hydrazine
Chlorobenzoyl chloride is dissolved in toluene, the solution for standby of 1mol/L is made, by the toluene solution of dimethyl adipate with
The flow of 30.5ml/min is injected in micro passage reaction or pipeline reactor by metering pump.By the molten of 80 mass % hydrazine hydrates
Liquid is injected in micro passage reaction or pipeline reactor by another metering pump with the flow velocity of 1.9ml/min, is reacted at 100 DEG C
2 seconds, micro passage reaction or pipeline reactor are flowed out, reaction mass is collected, obtains white powder crystallized product, content
99.7%, single hydrazine content 0.02%.Toluene divides water rear enclosure to use through filtering.
Embodiment 5
The preparation of winestone acid dihydrazide
Ethyl tartrate is dissolved in ethyl alcohol, the solution of 2mol/L is made, metering pump is passed through with the flow of 30ml/min
It injects in micro passage reaction or pipeline reactor.The hydrazine hydrate aqueous solution of 80 mass % by another metering pump with
It in the flow velocity injection micro passage reaction or pipeline reactor of 7.51ml/min, is reacted 3 seconds at 80 DEG C, outflow microchannel plate is answered
Device or pipeline reactor collect reaction mass, obtain white powder crystallized product, yield 99.1%, content 99.9%, single hydrazine
Content 0.01%.
Embodiment 6
The preparation of sebacic dihydrazide
Dimethyl sebacate is dissolved in methanol, the solution for standby of 1.5mol/L is made, the hydrazine hydrate of 80 mass % is molten
In methanol, the solution for standby of 3mol/L is made.In terms of the methanol solution of dimethyl sebacate is passed through by the flow of 50ml/min
Amount pump injection micro passage reaction or pipeline reactor in, by the methanol solution of hydrazine hydrate by another metering pump with
It in the flow velocity injection micro passage reaction or pipeline reactor of 63.1ml/min, is reacted 3 seconds at 60 DEG C, outflow microchannel plate is answered
Device or pipeline reactor collect reaction mass, obtain white crystalline product, yield 99.3%, content 99.9%, single hydrazine content
0.01%.Reaction mother liquor methanol is applied after filtering.
Embodiment 7
The preparation of phthalylhydrazine
Phthalic anhydride is dissolved in ethyl alcohol, the solution for standby of 2.5mol/L is made, 80 mass % hydrazine hydrates are dissolved in
In ethyl alcohol, the solution for standby of 2mol/L is made.The ethanol solution of phthalic anhydride is passed through into metering with the flow of 20ml/min
In pump injection micro passage reaction or pipeline reactor, by the ethanol solution of hydrazine hydrate by another metering pump with 25ml/min
Flow velocity injection micro passage reaction or pipeline reactor in, reacted 10 seconds at 80 DEG C, flow out micro passage reaction or pipeline
Reactor collects reaction mass, obtains white crystalline product, yield 99.1%, content 99.6%, single hydrazine content 0.02%.
Reaction mother liquor methanol is applied after filtering.
Embodiment 8
The preparation of two hydrazine of oxalyl
Dimethyl oxalate is dissolved in methanol, the solution for standby of 3mol/L is made, the hydrazine hydrate of 80 mass % is dissolved in first
In alcohol, the solution for standby of 3mol/L is made.The methanol solution of dimethyl oxalate is infused with the flow of 25ml/min by metering pump
Enter in micro passage reaction or pipeline reactor, by the methanol solution of hydrazine hydrate by another metering pump with 25.5ml/min's
Flow velocity injects in micro passage reaction or pipeline reactor, reacts 3 seconds at 80 DEG C, flows out micro passage reaction or pipe reaction
Device collects reaction mass, obtains white crystalline product, yield 99.4%, content 99.7%, single hydrazine content 0.01%.Reaction
Mother liquor methanol is applied after filtering.
Embodiment 9
The preparation of salicylyl hydrazine
Salethyl is dissolved in ethyl alcohol, the ethanol solution that 2.5mol/L is made is spare, and 80 mass % hydrazine hydrates are molten
In ethyl alcohol, the solution for standby of 2mol/L is made.The ethanol solution of salethyl is passed through into metering with the flow of 20ml/min
In pump injection micro passage reaction or pipeline reactor, by the ethanol solution of hydrazine hydrate by another metering pump with 25ml/min
Flow velocity injection micro passage reaction or pipeline reactor in, 70 DEG C react 4 seconds, flow out micro passage reaction or pipeline it is anti-
Device is answered, reaction mass is collected, obtains white powder crystallized product, yield 99.1%, content 99.8%.Reaction mother liquor ethyl alcohol warp
Rear enclosure is filtered to use.
Embodiment 10
The preparation of acethydrazide
Ethyl acetate is injected in micro passage reaction or pipeline reactor with the flow of 20ml/min by metering pump, it will
80 mass % hydrazine hydrates inject micro passage reaction or pipeline reactor by another metering pump with the flow velocity of 25.5ml/min
In, it is reacted 10 seconds at 85 DEG C, flows out micro passage reaction or pipeline reactor, collect reaction mass, falling-film distillation is collected and produced
Object, yield 99%, content 99.8%.
Embodiment 11
The preparation of isoniazid
The methanol solution that 2.5mol/L is made in pyridine-4-formic acid methyl esters is spare, and 80 mass % hydrazine hydrates are dissolved in methanol
In, the solution for standby of 2mol/L is made.The methanol solution of pyridine-4-formic acid methyl esters is passed through into metering pump with the flow of 20ml/min
It injects in micro passage reaction or pipeline reactor, by the methanol solution of hydrazine hydrate by another metering pump with 25.5ml/min
Flow velocity injection micro passage reaction or pipeline reactor in, 70 DEG C react 4 seconds, flow out micro passage reaction or pipeline it is anti-
Device is answered, reaction mass is collected, obtains white powder crystallized product, yield 95.6%, content 99.8%.Reaction mother liquor methanol warp
Rear enclosure is filtered to use.
Comparative example 1
The preparation of carbohydrazide
In 250mL flask, it is added the hydrazine hydrate aqueous solution of 28.1g 80%w at 20 DEG C, while by dimethyl carbonate
20.2g and methanol 60mL is configured to the methanol solution of dimethyl carbonate, spare.Stirring is opened, hydrazine hydrate aqueous solution is warming up to
75 DEG C, start the methanol solution that dimethyl carbonate is added dropwise, control is added dropwise within half an hour；Insulation reaction 3 hours, cooling,
Reaction mass is handled, white crystalline product, yield 88%, content 97.2%, single hydrazine content 2.1% are obtained.
Comparative example 2
The preparation of daminozide
In 250mL flask, 20 DEG C of whens, sequentially add unsymmetric dimethyl hydrazine 22.5g and methanol 50mL, stir evenly, and simultaneously will
Succinic anhydride 18.3g and methanol 50mL is configured to the methanol solution of succinic anhydride, spare.Stirring is opened, by unsymmetric dimethyl hydrazine
Methanol solution is warming up to 80 DEG C, starts the methanol solution that succinic anhydride is added dropwise, and control is added dropwise within half an hour；Insulation reaction
3 hours, cooling handled reaction mass, obtains white crystalline product, yield 85%, content 96.1%, double hydrazine contents 3.2%.
As can be seen from the above results, height is realized by using micro passage reaction or pipeline reactor in the present invention
Product yield and product content；On the contrary, do not use micro passage reaction or pipeline reactor, can only obtain low product yield and
Product content.
Claims (10)
1. a kind of continuous preparation method of hydrazides, it is characterised in that:
In micro passage reaction or pipeline reactor, make ester, acid anhydrides or acyl chlorides it is solvent-free lower or in a solvent with hydrazine or hydrazine
Solution successive reaction prepare hydrazide kind compound.
2. continuous preparation method according to claim 1, it is characterised in that: the structure of the hydrazide kind compound is as follows,
Wherein, R1~R4For hydrogen atom or saturated or unsaturated alkenyl group, cycloalkyl group, fragrance containing 1~18 carbon atom
Alkyl, heteroaryl alkyl or heteroalicyclyl, optionally containing one or more halogen atoms, nitro, carboxylic acid group, aldehyde on these groups
Base, sulfonic group or amino.
3. continuous preparation method according to claim 1 or 2, it is characterised in that: the solvent be selected from water, alcohols solvent,
Hydrocarbon solvent, halogenated hydrocarbon solvent, ketones solvent, nitrile solvents, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, two
Methyl sulfoxide.
4. continuous preparation method according to claim 1 or 2, it is characterised in that: the ester, acid anhydrides or acyl chlorides and the hydrazine
Equivalent proportion between 1:1.0~3.0, preferably between 1:1.0~1.5.
5. continuous preparation method according to claim 1 or 2, it is characterised in that: the ester, acid anhydrides or acyl chlorides are solvent-free
Or molar concentration is 0.01mol/L~5mol/L, preferably 0.1mol/L~3mol/L；The hydrazine is solvent-free or molar concentration is
0.01mol/L~5mol/L, preferably 0.1mol/L~3mol/L.
6. continuous preparation method according to claim 1 or 2, it is characterised in that: the micro passage reaction or pipeline are anti-
Answer the minimum spacing at the inner passage smallest cross-sectional of device not less than 1mm；The inner passage maximum of the micro passage reaction is cut
Maximum spacing at face is no more than 50mm.
7. continuous preparation method according to claim 1 or 2, it is characterised in that: the micro passage reaction or pipeline are anti-
Answer the reaction pressure of device between 1 bar~20 bars, preferably between 1 bar~10 bars.
8. continuous preparation method according to claim 1 or 2, it is characterised in that: the micro passage reaction or pipeline are anti-
Answer the reaction temperature of device between 10~250 DEG C, preferably between 50~150 DEG C.
9. continuous preparation method according to claim 1 or 2, it is characterised in that: the ester, acid anhydrides or acyl chlorides and the hydrazine
Or residence time of the solution of hydrazine in micro passage reaction or pipeline reactor is 1~300s, preferably 1~90s.
10. continuous preparation method according to claim 1 or 2, it is characterised in that: the micro passage reaction or pipeline are anti-
The structure for answering device includes cardioid, rectangle, trapezoidal, double trapezoid and irregular shape.
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| CN114213287A (en) * | 2021-12-30 | 2022-03-22 | 胜华新能源科技(东营)有限公司 | Process method for improving carbohydrazide yield |
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