[go: up one dir, main page]

CN1354175A - Preparation method of carbonyl alpha-substitution nitrogenous compound - Google Patents

Preparation method of carbonyl alpha-substitution nitrogenous compound Download PDF

Info

Publication number
CN1354175A
CN1354175A CN00132652A CN00132652A CN1354175A CN 1354175 A CN1354175 A CN 1354175A CN 00132652 A CN00132652 A CN 00132652A CN 00132652 A CN00132652 A CN 00132652A CN 1354175 A CN1354175 A CN 1354175A
Authority
CN
China
Prior art keywords
formula
reaction
phenyl
preparation
acetone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN00132652A
Other languages
Chinese (zh)
Other versions
CN1166652C (en
Inventor
罗必奎
张立塔
尹应武
文成贵
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Insight High Technology Beijing Co Ltd
Original Assignee
Insight High Technology Beijing Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Insight High Technology Beijing Co Ltd filed Critical Insight High Technology Beijing Co Ltd
Priority to CNB00132652XA priority Critical patent/CN1166652C/en
Priority to CNA018179630A priority patent/CN1471506A/en
Priority to PCT/CN2001/001578 priority patent/WO2002042254A1/en
Priority to AU2002221500A priority patent/AU2002221500A1/en
Publication of CN1354175A publication Critical patent/CN1354175A/en
Application granted granted Critical
Publication of CN1166652C publication Critical patent/CN1166652C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C337/00—Derivatives of thiocarbonic acids containing functional groups covered by groups C07C333/00 or C07C335/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
    • C07C337/06—Compounds containing any of the groups, e.g. thiosemicarbazides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C337/00—Derivatives of thiocarbonic acids containing functional groups covered by groups C07C333/00 or C07C335/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
    • C07C337/06—Compounds containing any of the groups, e.g. thiosemicarbazides
    • C07C337/08—Compounds containing any of the groups, e.g. thiosemicarbazides the other nitrogen atom being further doubly-bound to a carbon atom, e.g. thiosemicarbazones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • C07D295/04—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 substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/10—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
    • C07D295/104—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • 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
    • C07D295/04—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 substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/10—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
    • C07D295/104—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/108—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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
    • C07D295/04—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 substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/10—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
    • C07D295/112—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 substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

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

Abstract

The present invention relates to a method for preparing carbonyl alpha-substituted nitrogenous compound. Said method includes that in the presence of Lewis acid, it makes alpha-halogenated ketone or alpha-halogenated aldehyde react with primary amine, secondary amine or heterocyclic compound containing nitrogen atom.

Description

The preparation method of carbonyl alpha-substituted nitrogen compounds
The present invention relates to a kind of method for preparing carbonyl alpha-substituted nitrogen compounds of novelty, this method comprises, in the presence of lewis acidic, make α-Lu Daitong or alpha-halogen aldehyde and primary amine, secondary amine or contains the heterogeneous ring compound reaction of nitrogen-atoms.
At present, usually with α-Lu Daitong or alpha-halogen aldehyde and primary amine, secondary amine or contain the heterogeneous ring compound reaction of nitrogen-atoms, the method for generation carbonyl alpha-substituted nitrogen compounds mainly contains direct method and epoxy intermediate method.
Wherein direct method is that α-Lu Daitong or alpha-halogen aldehyde and primary amine, secondary amine or the heterogeneous ring compound direct reaction that contains nitrogen-atoms generate carbonyl alpha-substituted nitrogen compounds.This method since primary amine, secondary amine or the heterogeneous ring compound that contains nitrogen-atoms both can with the halogen generation substitution reaction on the 2-position, also can react with the carbonyl carbon on the 1-position, and temperature is high more, and with easy more the carrying out of carbonyl carbon reaction on the 1-position, promptly by product is many more.
For example Japanese Patent JP 10114736 has reported the direct and morpholine reaction by 2-chloro-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone, refluxed 10 hours down at 130 ℃, obtain 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone, reaction yield is 87.9%.It reacts formula as follows:
Figure A0013265200041
The epoxy intermediate method is that α-Lu Daitong or alpha-halogen aldehyde generate the oxirane compound intermediate with the sodium methylate reaction earlier, and this intermediate generates carbonyl alpha-substituted nitrogen compounds with primary amine, secondary amine or the heterogeneous ring compound reaction that contains nitrogen-atoms again.This method is because the easy hydrolysis of α-Lu Daitangjihuahewu generates oxy-compound, the epoxy compounds instability, need definitely anhydrous to raw material α-Lu Daitangjihuahewu, sodium methylate and nitrogenous compound, and want strictness to control reaction conditions, so the reaction yield fluctuation is bigger, product quality is difficult to guarantee.
U.S. Pat-A-2 for example, 827,460 have reported by 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone and sodium methylate reaction generation epoxy compounds 3,3-dimethyl-2-methoxyl group-2-(4-methylthio group phenyl) oxyethane intermediate, this intermediate reacted 15 hours under reflux temperature with morpholine again, obtained 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone.Its reaction scheme
Figure A0013265200051
Formula as follows:
Because this patent do not report yield, the contriver is through experimental results show that: water content is too high in, the morpholine too high as free alkali in the sodium methylate all can have a significant impact reaction; Under the absolute anhydrous situation of raw material of reaction, epoxy compounds and morpholine react under reflux temperature and then can generate more by product in 15 hours.
In addition, Japanese Patent JP 63,192,744, U.S. Pat 3,465, and 039, U.S. Pat 3,314,970, USSR (Union of Soviet Socialist Republics) patent SU 225,203, USSR (Union of Soviet Socialist Republics) patent SU 230,827, ZA 6801749, Stefanescu, Paul is in Rev.Chim. (Bucharest) (1968), 19 (11), 639 and Hahn, people such as Hob-Gyu are at Han ' guk Nonghwa Hakhoechi (1997), have reported such reaction in 40 (2), 139.
In sum, adopt direct method or epoxy intermediate legal system be equipped with carbonyl alpha-substituted nitrogen compounds all exist to raw materials quality require high, temperature of reaction is high, long reaction time, reaction orientation poor selectivity and yield problem on the low side.
The present invention has existed on the insufficient basis having summed up aforesaid method, through a large amount of experiments and dynamically trace analysis discovery, under the situation that has Lewis acid to exist, α-Lu Daitong or alpha-halogen aldehyde can be earlier and Lewis acid form complex compound, even under very low temperature, this complex compound also can generate.Because α-Lu Daitong or alpha-halogen aldehyde and Lewis acid form complex compound, and the reactive behavior of alpha-position halogen atom is increased greatly, thereby improved α-Lu Daitong or alpha-halogen aldehyde and primary amine, secondary amine or contained the selectivity of the heterogeneous ring compound reaction of nitrogen-atoms, obtain extraordinary effect, thereby finished the present invention.
Operating process of the present invention is: having under solvent or the solvent-free condition, formula (II) α-Lu Daitangjihuahewu (α-Lu Daitong or alpha-halogen aldehyde) and formula (III) amine compound (primary amine, secondary amine or contain the heterogeneous ring compound of nitrogen-atoms) and Lewis acid mix stirring, 0 ℃-120 ℃ reactions down, generally can transform fully with interior raw material at 0.5-20 hour, the converted in-situ rate obtains product near 100% after aftertreatment, purification.
Specifically, the invention provides the preparation method of a kind of general formula (I) compound,
R 1R 2-C(Q)-COR 5 (I)
In the formula:
R 1, R 2And R 5Represent hydrogen, C independently of each other 1-C 8-alkyl, phenyl, substituted-phenyl or not
Five yuan or hexa-member heterocycle base of nitrogen atom;
Q representative-NR 3R 4,
Wherein
R 3And R 4Represent hydrogen, C independently of each other 1-C 8-alkyl, phenyl, substituted-phenyl, or R 3
And R 4Coupled nitrogen-atoms forms together and contains a nitrogen-atoms at least as assorted former
Five yuan or hexa-member heterocycle base of son; Described method comprises: in the presence of lewis acidic, make the reaction of formula (II) α-Lu Daitangjihuahewu and formula (III) amine compound,
R 1R 2-CX 1COR 5 (II)
In the formula:
R 1, R 2And R 5As defined above,
X 1Represent fluorine, chlorine or bromine,
Q-H (III)
In the formula:
Q as defined above.
The present invention preferably provides the preparation method of a kind of general formula (I) compound,
R 1R 2-C(Q)-COR 5 (I)
In the formula:
R 1, R 2And R 5Represent hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, aryl independently of each other, by one to three C 1-C 8-alkyl, C 1-C 8-haloalkyl, C 1-C 8-alkoxyl group, C 1-C 8Aryl that-alkylthio replaces or five yuan or hexa-member heterocycle base of nonnitrogenous atom;
Q representative-NR 3R 4,
Wherein
R 3And R 4Preferably represent hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, aryl independently of each other, or R 3And R 4Coupled nitrogen-atoms forms following heterocyclic radical together: pyrryl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, piperidyl, pyridyl, pyrimidyl, morpholinyl etc., described method comprises: in the presence of lewis acidic, make the reaction of formula (II) α-Lu Daitangjihuahewu and formula (III) amine compound
R 1R 2-CX 1COR 5 (II)
In the formula:
R 1, R 2And R 5As defined above,
X 1Represent fluorine, chlorine or bromine,
Q-H (III)
In the formula
Q as defined above.
In the methods of the invention, Lewis acid is selected from following: boron trifluoride, aluminum chloride, zinc chloride, iron trichloride, tin chloride, cupric chloride, titanium tetrachloride or polyphosphoric acid or the like.
When carrying out the present invention and reacting, can select stock yard and lewis acidic mol ratio as required.During reaction, the formula that can adopt (II) α-Lu Daitangjihuahewu, formula (III) amine compound and lewis acidic mol ratio are 1: 0.2-30: 0.01-10, preferred molar ratio is 1: 0.5-5: 0.1-2.
The inventive method can be reacted in wide relatively temperature range, and temperature of reaction can be 0 ℃-120 ℃, and preferably 10 ℃-60 ℃, the reaction times is 0.5-20 hour.
The inventive method has following characteristics:
1. technological operation of the present invention is simple, and equipment is not had particular requirement, is easy to suitability for industrialized production.
2. the present invention compares the reaction conditions gentleness with other method.Generally only need 10 ℃-60 ℃ and just can react well, take place, simultaneously, reached energy saving purposes thereby reduce side reaction.
3. the present invention compares with other method, has shortened the reaction times greatly, and adding raw material only needed just can react completely in 2-5 hour, had improved plant factor and production capacity effectively.
4. the present invention is by selecting Lewis acid as reaction promoter, makes converted in-situ rate that feedstock conversion becomes product near 100%, thereby improved reaction yield effectively.
5. the present invention can save some steps of aftertreatment, thereby simplify operation steps because the impurity that produces in the reaction is less.
The present invention can be as the case may be few with or even do not use solvent, thereby the reduction raw materials cost.
The present invention also will be further described by following examples and comparative examples, but these embodiment to should not be construed as be limitation of the present invention.
Embodiment 1
The inventive method prepares 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone
1. the preparation of isobutyryl chloride
Weighing 176g (2mol) isopropylformic acid is added to 137g (1mol) phosphorus trichloride in the above-mentioned solution, reacts 8 hours.Tell the upper strata after the reaction, obtain isobutyryl chloride after the rectifying.
2. the preparation of 2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone
Weighing 248g (2mol) thioanisole, 250ml oil of mirbane stirred 1 hour behind adding 267g (2mol) aluminum chloride, added isobutyryl chloride reaction 1 hour, add in the sour water earlier and wash, add alkali cleaning again, layering obtains 2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone behind the organic phase precipitation.
3. the preparation of 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone
With 386g (2mol) 2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone solution in the 400ml tetracol phenixin, 320g (2mol) liquid bromine slowly is added drop-wise in the solution that disposes above with after the 270ml tetracol phenixin dilution, dropwises the back and stir to make in one hour and react completely.Nitrogen blowing is driven dissolved bromize hydrogen gas in the solution away, steam to obtain the 524g product after desolventizing, content 97.8%, above three step total recoverys be 93.8%.
4. the preparation of 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone
(98.7% content, 0.5mol) 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone and 500ml sherwood oil add 174g (2mol) morpholine to weighing 143g, add aluminum chloride 13.4g, and 50 ℃ were reacted 5 hours.Add the hydrochloric acid adjust pH about 2, after the layering water is added 30% liquid caustic soda adjust pH to alkalescence, separate out faint yellow solid, get crude product after the filtration,, be weighed as 130g after filtration is dried with getting the canescence crystallization behind the mixed solvent recrystallization, content 99.4%, yield 92.7%.
Comparative examples 1
Direct method prepares 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone
1. the preparation of 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone
The preparation of 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone is with embodiment 1.
2. the preparation of 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone
(98.7% content, 0.5mol) 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone add 200ml dimethylbenzene and 174g (2mol) morpholine to weighing 143g, and reflux state reacted 10 hours down.Add the hydrochloric acid adjust pH about 2, with twice of xylene extraction, after the layering water is added 30% liquid caustic soda adjust pH to alkalescence, separate out faint yellow solid, get crude product after the filtration,, be weighed as 92.2g after filtration is dried with getting the canescence crystallization behind the mixed solvent recrystallization, content 98.9%, yield 65.3%.
Comparative examples 2
Adopt the epoxy intermediate legal system to be equipped with 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone
1. the preparation of 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone
The preparation of 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone is with embodiment 1.
2. 3, the preparation of 3-dimethyl-2-methoxyl group-2-(4-methylthio group phenyl) oxyethane
29.7g (0.55mol) sodium methylate is dissolved in the 150ml methyl alcohol, be heated with stirring to backflow, weighing 143g (98.7% content, 0.5mol) 2-bromo-2-methyl isophthalic acid-(4-methylthio group phenyl)-1-acetone solution is in 100ml methyl alcohol, drips of solution after the dissolving is added in the sodium methoxide solution, dropwise the back backflow and stir 1h down, the distillating carbinol solvent, residuum is poured in the frozen water, with extracted with diethyl ether after washing ether layer once, anhydrous sodium sulfate drying concentrates back underpressure distillation cooling and obtains epoxy compounds 3, the pure product of crystal of 3-dimethyl-2-methoxyl group-2-(4-methylthio group phenyl) oxyethane.
3. the preparation of 2-methyl isophthalic acid-(4-methylthio group phenyl)-2-morpholine-1-acetone
To 3, add 348g (4mol) morpholine in 3-dimethyl-2-methoxyl group-2-(the 4-methylthio group phenyl) oxyethane, be heated to reflux state reaction 15 hours.Steam except that behind the morpholine and use extracted with diethyl ether, extraction liquid adds 10% aqueous hydrochloric acid adjust pH about 2, after the layering water is added 30% liquid caustic soda and regulate the pH value about 13, again with concentrating after the extracted with diethyl ether, use ethyl alcohol recrystallization then, obtain the canescence crystallization, be weighed as 101g after filtration is dried, 98.3%, two step of content total recovery is 71.6%.
Embodiment 2
The preparation of 2-methyl isophthalic acid-phenyl-2-morpholine-1-acetone
1. the preparation of isobutyryl chloride
Weighing 176g (2mol) isopropylformic acid is added to 137g (1mol) phosphorus trichloride in the above-mentioned solution, reacts 8 hours.Tell the upper strata after the reaction, obtain isobutyryl chloride after the rectifying.
2. the preparation of 2-methyl isophthalic acid-phenyl-1-acetone
Weighing 312g (4mol) benzene stirred 1 hour behind adding 267g (2mol) aluminum chloride, added isobutyryl chloride reaction 1 hour, washed in the adding sour water earlier, added alkali cleaning again, and layering obtains 2-methyl isophthalic acid-phenyl-1-acetone behind the organic phase precipitation.
3. the preparation of 2-chloro-2-methyl isophthalic acid-phenyl-1-acetone
2-methyl isophthalic acid-phenyl-1-acetone solution in the 400ml tetracol phenixin, is slowly fed chlorine down at 10 ℃-15 ℃, and logical chlorine stirs after 10 hours to make in two hours and reacts completely.Nitrogen blowing is driven dissolved hydrogen chloride gas in the solution away, obtains the 342g product after steaming desolventizes, content 96.3%, and last three step total recoverys are 90.2%.
4. the preparation of 2-methyl isophthalic acid-phenyl-2-morpholine-1-acetone
(96.3% content, 0.5mol) 2-chloro-2-methyl isophthalic acid-phenyl-1-acetone and 200ml oil of mirbane add 174g (2mol) morpholine to weighing 94.8g, add aluminum chloride 13.4g, and 50 ℃ were reacted 4 hours.Add the hydrochloric acid adjust pH, after the layering water is added the adjusting PH with base value to the alkaline crude product that gets, get product, be weighed as 104g, content 99.5%, yield 89.1% through aftertreatment.
Embodiment 3
The preparation of 2-methyl-2-imidazoles propionic aldehyde
Weighing 36.0g (0.5mol) 2-chloro-2 methyl propanal and 50ml sherwood oil add 47.6g (0.7mol) imidazoles, add zinc chloride 13.6g, and 60 ℃ were reacted 5 hours.Get product through aftertreatment, be weighed as 63.2g, content 98.7%, yield 90.4%.
Embodiment 4
The preparation of 2-methyl isophthalic acid-phenyl-2-n-propylamine base-1-acetone
91.3g (0.5mol) 2-chloro-2-methyl isophthalic acid-phenyl-1-acetone, 32.5g (0.55mol) Tri N-Propyl Amine are added in the 60ml ethylene dichloride, add zinc chloride 13.6g then, reacted 3 hours down at 40 ℃.Get product through aftertreatment, be weighed as 91.3g, content 98.4%, yield 87.6%.
Embodiment 5
The preparation of 1-diethylin cyclohexyl phenyl ketone
111.8g (0.5mol) 1-chloro cyclohexyl phenyl ketone, 43.8g (0.6mol) diethylamine are added in the 100ml sherwood oil, add aluminum chloride 13.4g then, reacted 4 hours down at 45 ℃.Get product through aftertreatment, be weighed as 116.2g, content 99.4%, yield 89.2%.

Claims (5)

1. method for preparing general formula (I) compound,
R 1R 2-C(Q)-COR 5 (I)
In the formula:
R 1, R 2And R 5Represent hydrogen, C independently of each other 1-C 8-alkyl, phenyl, substituted-phenyl or not
Five yuan or hexa-member heterocycle base of nitrogen atom;
Q representative-NR 3R 4,
Wherein
R 3And R 4Represent hydrogen, C independently of each other 1-C 8-alkyl, phenyl, substituted-phenyl, or R 3And R 4Coupled nitrogen-atoms forms together and contains a nitrogen-atoms at least as heteroatomic five yuan or hexa-member heterocycle base; It is characterized in that: in the presence of lewis acidic, make the reaction of formula (II) α-Lu Daitangjihuahewu and formula (III) amine compound,
R 1R 2-CX 1COR 5 (II)
In the formula:
R 1, R 2And R 5As defined above, X 1Represent fluorine, chlorine or bromine,
Q-H (III)
In the formula
Q as defined above.
2. according to the process of claim 1 wherein, Lewis acid is selected from: boron trifluoride, aluminum chloride, zinc chloride, iron trichloride, tin chloride, cupric chloride, titanium tetrachloride or polyphosphoric acid or the like.
3. according to arbitrary method of claim 1-2, wherein, formula (II) α-Lu Daitangjihuahewu, formula (III) amine compound and lewis acidic mol ratio are 1: 0.2-30: 0.01-10.
4. according to arbitrary method of claim 1-3, wherein, temperature of reaction is 0 ℃-120 ℃.
5. according to arbitrary method of claim 1-4, wherein, the reaction times is 0.5-20 hour.
CNB00132652XA 2000-11-21 2000-11-21 Preparation method of carbonyl alpha-substitution nitrogenous compound Expired - Fee Related CN1166652C (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CNB00132652XA CN1166652C (en) 2000-11-21 2000-11-21 Preparation method of carbonyl alpha-substitution nitrogenous compound
CNA018179630A CN1471506A (en) 2000-11-21 2001-11-21 Process for producing carbonyl alpha-substituted nitrogen-containing compound
PCT/CN2001/001578 WO2002042254A1 (en) 2000-11-21 2001-11-21 PROCESS OF PRODUCING CARBONYL a-SUBSTITUTED NITROGEN-CONTAINING COMPOUNDS
AU2002221500A AU2002221500A1 (en) 2000-11-21 2001-11-21 Process of producing carbonyl a-substituted nitrogen-containing compounds

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNB00132652XA CN1166652C (en) 2000-11-21 2000-11-21 Preparation method of carbonyl alpha-substitution nitrogenous compound

Publications (2)

Publication Number Publication Date
CN1354175A true CN1354175A (en) 2002-06-19
CN1166652C CN1166652C (en) 2004-09-15

Family

ID=4595293

Family Applications (2)

Application Number Title Priority Date Filing Date
CNB00132652XA Expired - Fee Related CN1166652C (en) 2000-11-21 2000-11-21 Preparation method of carbonyl alpha-substitution nitrogenous compound
CNA018179630A Pending CN1471506A (en) 2000-11-21 2001-11-21 Process for producing carbonyl alpha-substituted nitrogen-containing compound

Family Applications After (1)

Application Number Title Priority Date Filing Date
CNA018179630A Pending CN1471506A (en) 2000-11-21 2001-11-21 Process for producing carbonyl alpha-substituted nitrogen-containing compound

Country Status (3)

Country Link
CN (2) CN1166652C (en)
AU (1) AU2002221500A1 (en)
WO (1) WO2002042254A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101659644B (en) * 2008-08-26 2011-04-20 天津英力科技发展有限公司 Method for synthesizing 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanon
CN102241645A (en) * 2011-05-27 2011-11-16 天津久日化学股份有限公司 Preparation method of 2-methyl-2-(4-morpholinyl)-1-[4-(methylthio)phenyl]-1-acetone
CN102659717A (en) * 2012-04-20 2012-09-12 浙江启明药业有限公司 Synthetic method of 2-methyl-1-(4'-methylthiophenyl)-2-morpholinyl-1-acetone
CN103242261A (en) * 2013-05-21 2013-08-14 湖北工业大学 Synthetic method of alpha-amino aromatic ketone compound
CN104327220B (en) * 2014-10-17 2017-06-13 武汉理工大学 A kind of preparation method of polyacrylic acid based water reducer

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1799638B1 (en) * 2004-09-29 2008-07-30 Ciba Holding Inc. Process for preparing aromatic thiophenyl ketones

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10114736A (en) * 1996-10-09 1998-05-06 Sumitomo Seika Chem Co Ltd Production of 2-methyl-1-(4-(alkylthio)phenyl)-2-morpholino-1-propanone

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101659644B (en) * 2008-08-26 2011-04-20 天津英力科技发展有限公司 Method for synthesizing 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanon
CN102241645A (en) * 2011-05-27 2011-11-16 天津久日化学股份有限公司 Preparation method of 2-methyl-2-(4-morpholinyl)-1-[4-(methylthio)phenyl]-1-acetone
CN102241645B (en) * 2011-05-27 2013-09-25 天津久日化学股份有限公司 Preparation method of 2-methyl-2-(4-morpholinyl)-1-[4-(methylthio)phenyl]-1-acetone
CN102659717A (en) * 2012-04-20 2012-09-12 浙江启明药业有限公司 Synthetic method of 2-methyl-1-(4'-methylthiophenyl)-2-morpholinyl-1-acetone
CN102659717B (en) * 2012-04-20 2014-04-16 浙江启明药业有限公司 Synthetic method of 2-methyl-1-(4'-methylthiophenyl)-2-morpholinyl-1-acetone
CN103242261A (en) * 2013-05-21 2013-08-14 湖北工业大学 Synthetic method of alpha-amino aromatic ketone compound
CN104327220B (en) * 2014-10-17 2017-06-13 武汉理工大学 A kind of preparation method of polyacrylic acid based water reducer

Also Published As

Publication number Publication date
CN1471506A (en) 2004-01-28
WO2002042254A1 (en) 2002-05-30
AU2002221500A1 (en) 2002-06-03
CN1166652C (en) 2004-09-15

Similar Documents

Publication Publication Date Title
CN1209349C (en) Sulfonium salt and preparation method thereof
CN113773182B (en) Method for synthesizing 6, 8-dichloro octanoate
CN1166652C (en) Preparation method of carbonyl alpha-substitution nitrogenous compound
CN1073096C (en) Process for preparation of 2 -chloro -5 -cholromethyl -1, 3 -thiazole
CN101066926A (en) Prepn process of 3-trifluoro methyl benzoate
CN1095823C (en) Process for synthesizing benzoic acids
JP2003500461A (en) Synthesis of bis (alkylcyclopentagenenyl) metallocene
CN1680365A (en) Novel synthesis and crystallization of piperazine ring-containing compounds
JP5588130B2 (en) Method for producing methylenebis (benzotriazolylphenol) compound
CN1956941A (en) Method for preparing 1,3-dibromoacetone, 1,3-dichloroacetone and epichlorohydrin
CN101100450A (en) Method for preparing ethylsulfonyl acetonitrile
CN1196665C (en) Preparation method of 5-[(4-chlorophenyl)methyl]-2,2-dimethylcyclopentanone
CN1027258C (en) Method for synthesizing acyl cyanide
CN107602337B (en) Preparation method of 1,4-dicyano-2-butene
WO2024190326A1 (en) Method for producing organic compound
CN114773324B (en) Preparation method of difenoconazole
CN1844077A (en) 1-Chloro-2-methyl-4-alkanoyloxy-2-butene preparation method
CN105801484A (en) Preparation method of pyrazolyl acrylonitrile compound
CN114213248A (en) Preparation method of 4-benzyloxy phenyl ethyl n-decanoate
CN100338015C (en) Glycol ester compound for preparing catalyst for olefinic polymerization
CN115745973A (en) Preparation method of difenoconazole
CN1029121C (en) Method for preparation of phenol
CN1990458A (en) Process for preparing 4.4-difluoro-2-amino butyric acid with optical activity and ester thereof
CN1847231A (en) Process of preparing aromatic ring substituted ixooxazoline compound
CN108976100B (en) Synthesis method of diphenylcyclohexyl methanol

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C14 Grant of patent or utility model
GR01 Patent grant
EE01 Entry into force of recordation of patent licensing contract

Assignee: Insight High Technology (Tianjin) Co., Ltd.

Assignor: Yingli Science and Technology Development Co., Ltd., Beijing

Contract fulfillment period: 2009.1.1 to 2019.12.31 contract change

Contract record no.: 2009120000005

Denomination of invention: Method for preparing carbonyl alpha-substituted nitrogen compounds

Granted publication date: 20040915

License type: Exclusive license

Record date: 2009.3.17

LIC Patent licence contract for exploitation submitted for record

Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.1.1 TO 2019.12.31; CHANGE OF CONTRACT

Name of requester: TIANJIN YINGLI TECHNOLOGICAL DEVELOPMENT CO., LTD.

Effective date: 20090317

C56 Change in the name or address of the patentee
CP02 Change in the address of a patent holder

Address after: Beijing City, Haidian District Zhongguancun 100190 South 1 1 horse Baxter 10 storey building

Patentee after: Yingli Science and Technology Development Co., Ltd., Beijing

Address before: 100084, Tsinghua University, Beijing, purple building, four floor

Patentee before: Yingli Science and Technology Development Co., Ltd., Beijing

DD01 Delivery of document by public notice
DD01 Delivery of document by public notice

Addressee: Yingli Science and Technology Development Co., Ltd., Beijing

Document name: Notification of Termination of Patent Right

CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20040915

Termination date: 20161121