CN86103229A - The preparation method of 2-thiochromene fork acetylacetic ester - Google Patents
The preparation method of 2-thiochromene fork acetylacetic ester Download PDFInfo
- Publication number
- CN86103229A CN86103229A CN198686103229A CN86103229A CN86103229A CN 86103229 A CN86103229 A CN 86103229A CN 198686103229 A CN198686103229 A CN 198686103229A CN 86103229 A CN86103229 A CN 86103229A CN 86103229 A CN86103229 A CN 86103229A
- Authority
- CN
- China
- Prior art keywords
- following
- carbon atoms
- line style
- type alkyl
- branching type
- 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.)
- Pending
Links
- 150000002148 esters Chemical class 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- -1 acetoxyl groups Chemical group 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 150000001721 carbon Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 239000003701 inert diluent Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 7
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- OENLEHTYJXMVBG-UHFFFAOYSA-N pyridine;hydrate Chemical class [OH-].C1=CC=[NH+]C=C1 OENLEHTYJXMVBG-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- QCDJOJKIHZQJGX-UHFFFAOYSA-N 1-nitropropan-2-one Chemical compound CC(=O)C[N+]([O-])=O QCDJOJKIHZQJGX-UHFFFAOYSA-N 0.000 description 1
- ONJRTQUWKRDCTA-UHFFFAOYSA-N 2h-thiochromene Chemical compound C1=CC=C2C=CCSC2=C1 ONJRTQUWKRDCTA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101100004280 Caenorhabditis elegans best-2 gene Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
- 235000015076 Shorea robusta Nutrition 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- RIBFXMJCUYXJDZ-UHFFFAOYSA-N propanoyl bromide Chemical compound CCC(Br)=O RIBFXMJCUYXJDZ-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
2-thiochromene fork acetylacetic ester (I) with following molecular formula, herein, R
1Represent line style that 4 carbon atoms are following or branching type alkyl, R
2Represent line style or branching type alkyl that 4 carbon atoms are following, it can be replaced arbitrarily by halogen or 7 acetoxyl groups below the carbon atom.Can be by Schiff's base with above-mentioned molecule formula II.Herein: R
3Represent line style or branching type alkyl that 6 carbon atoms are following.
Produce with acetylacetic ester reaction with following molecular formula,
Herein: R
1And R
2Meaning is the same.Reaction is preferably under organic inert diluent and the acylating agent existence to be carried out.
Description
The present invention relates to the method for making of the less 2-thiochromene fork acetylacetic ester of knowing, it can be used for making the various active medical compounds.
Known 3-oxo-1-(4-oxo-2-phenyl-4 hydrogen-thiochromene-8-yl)-1-butylene-2-carboxylicesters is to be made by 4-oxo-2-benzyl-4 hydrogen-thiochromene-8-carbonyl aldehyde and corresponding acetylacetic ester by the Knoevenagel condensation reaction (to see european patent application 123,112), but because the solvability of this aldehyde is bad, and make this method for making complexity, and yield is very low.
Known 1-phenyl-2-nitro but-1-ene-3-ketone and their phenyl substituted derivative can get with corresponding Schiff's base (azomethine) reaction with nitro acetone (sees A.Dornow, W.Sassenberg, Liebigs Ann.Chem.602,14～23(1957)).
We also know acetylacetic ester and aromatic azomethine, no matter use acid catalyst, or alkaline catalysts, all can not obtain desirable benzyl fork compound with single stage method.(see Chemical Abstracts 79,126279; 85,77,829).
The molecular formula of now having learnt 2-thiochromene fork acetylacetic ester is as follows:
Herein: R
1Represent line style or branching type alkyl that 4 carbon atoms are following;
R
2Represent line style or branching type alkyl that 4 carbon atoms are following, it can be replaced arbitrarily by halogen or 7 acyloxy below the carbon atom.
Its available Schiff's base with following logical formula II
Herein: R
3Represent line style or branching type alkyl that 6 carbon atoms are following,
Produce with the acetylacetic ester reaction of following logical formula III,
Herein: R
1And R
2Meaning is the same.
Reaction is preferably under organic inert diluent and the acylating agent existence to be carried out.
Beyond thought is can obtain the finished product (I) by one step of method of the present invention, from formal document of past, do not reckon with that benzyl fork compound can easily obtain yield yet, do not reckon with that also azomethine can be so easily and a lot of thiochromene radical reactions.
The present invention has the advantage of single step reaction, easy reaction, and in addition, product is easy to processing and refining.
Usually represent R in this molecular formula with the molecule formula I with the compound that the present invention makes
1Following line style or branching type alkyl of 4 carbon atoms preferably;
R
2Preferably 4 line style or branching type alkyl that carbon atom is following, or brooethyl, chloromethyl, acetoxy-methyl, benzoyloxy group methyl.
If with 8-just-butyl iminomethyl-4-oxo-2-phenyl-4 hydrogen-thiochromene and methyl acetoacetate are as initial substance, then reaction process can be represented by the formula:
Can produce with currently known methods as the acetylacetic ester with molecule formula III of initiator and (to see D.Borrmarnn, " Methoden der Organischen Chemie " VII/4 of Houben-Weyl, 230et seq(1968), S.Gelin, P.Pollet, Synth.Commun.1980,805; With Tetrahedron 34,1453(1978)).
The Schiff's base with molecule formula II as initiator is novel, and they can be at 0～60 ℃, preferably at room temperature with the 4-oxo-2-phenyl-4 hydrogen-thiochromene-8-carbonyl aldehyde with molecular formula (IV)
React with amine and make with molecular formula (V).
R
3-NH
2（Ⅴ）
Herein: R
3Meaning is the same.
Be reflected in the organic solvent and carry out, alcohols (methyl alcohol, ethanol, propyl alcohol) for example, chlorinated hydrocarbons (methylene dichloride, chloroform, tetracol phenixin) or aromatic hydrocarbons (benzene,toluene,xylene).Preferably use methylene dichloride, chloroform to make solvent.It is then better to add absorbent materials such as resembling sodium sulfate, salt of wormwood, sal epsom, molecular sieve.Filtering out additive, remove desolvate or solvent-water mixture after, crystallizablely go out Schiff's base.
The acylating agent that is suitable for the present invention's use is conventional acylating agent, preferably carboxylic acid anhydride; For example diacetyl oxide, propionic anhydride; Or carboxylic acid halides: for example Acetyl Chloride 98Min., acetyl bromide, propionyl chloride, propionyl bromide.Diacetyl oxide is good especially acylating agent.
Reaction can be carried out having under thinner or the diluent free, and suitable diluent is conventional inert solvent, and aromatic hydrocarbons preferably is as benzene,toluene,xylene; Carboxylic acid is as formic acid, acetate, propionic acid; Chlorinated hydrocarbons is as methylene dichloride, chloroform, tetracol phenixin.Be reflected at 0～200 ℃, be preferably under 10～150 ℃ of temperature and carry out.
Be reflected under the normal pressure, also can carry out adding to depress, under normal pressure, carry out usually.
Each mole Schiff's base (II) uses 0.1～10 mole of (preferably 1-5 mole) acetylacetic ester (III) and 1～10 mole of (best 2～6 moles) acylating agent among the present invention.Reaction is preferably used and is surpassed 6 moles excessive acetic anhydride via, and this moment, diacetyl oxide was a solvent, was again acylating agent.
Compound with molecule formula I simply mode and enamine or acetylacetic ester and the two pyridinium hydroxides of amine reaction being transformed into 1.4-(see A.Hantzsch, Liebigs Ann.Chem 215,1,1882; And U.Eisner, J.Kuthan, Chem, Rev 72(1972)).
These pairs pyridinium hydroxide has constituted precious active pharmaceutical compounds, can be used as the shrinkability that cardiotonic drug is improved cardiac muscle.In addition,, can be used as anti-hypopiesia agent,, reduce mucous membrane swelling and improve salt and the balance of liquid (seeing European patent 123,112 and 123,095) with lowering blood glucose because they can increase the calcium influx in the cell.
Below be examples more of the present invention, do not further develop but do not limit it.
The preparation example
Example 1
A) 8-just-butyl iminomethyl-4-oxo-2-phenyl-4 hydrogen-thiochromene
752 gram (2.83 moles) 4-oxo-2-phenyl-4 hydrogen-thiochromene-8-carbonyl aldehyde batch dissolution in 4.25 liters of methylene dichloride, are added 420 milliliters of (4.25 moles) n-Butyl Amine 99s again, and partly reaction water is isolated in dissolving fully after the stirred for several hour.Then, vacuum concentrated mixture.2 liters of methylene dichloride of each adding evaporate three times, repeatedly to remove remaining butylamine fully.Oil reservoir crystallization when cooling.
B) 4-acetoxy-3-oxo-1-(4-oxo-2-phenyl-4 hydrogen-thiochromene-8-yl)-1-butylene-2-carboxylic acid, ethyl ester
920 gram (2.83 moles) cymogene base imino-compounds (1a) and 585 gram (3.11 moles) acetoxy acid ethyl ester and 525 milliliters of (5.66 moles) diacetyl oxide intense mixing.Adopt exterior cooling, temperature raises behind the several minutes.One when temperature decline, promptly stops exterior cooling.Add crystal seed, through stirring, mixture produces crystallization, the stirred crystallization material, and then in suction strainer to the glass frosted funnel, and successively clean with 1: 1 toluene/sherwood oil and sherwood oil rinsing.
Productive rate: 758 grams (theoretical value 61.5%)
Fusing point: 135 ℃ (suitable/anti-isomer mixture)
Following substances preparation method is similar to this reaction method:
Example 2
3-oxo-1-(4-oxo-2-phenyl-4 hydrogen-thiochromene-8-yl)-1-butylene-2-carboxylate methyl ester
Productive rate: 73% of theoretical value
Fusing point: 155 ℃ (suitable/anti-isomer mixture)
Example 3
4-chloro-3-oxo-1-(4-oxo-2-phenyl-4 hydrogen-thiochromene-8-yl)-1-butylene-2-carboxylic acid isopropyl
Productive rate: 67% of theoretical value
Fusing point: 76 ℃ (suitable/anti-isomer mixture)
Example 4
4-chloro-3-oxo-1-(4-oxo-2-phenyl-4 hydrogen-thiochromene-8-yl)-1-butylene-2-carboxylic acid, ethyl ester
Productive rate: 61% of theoretical value
Fusing point: 89 ℃ (suitable/anti-isomer mixture)
Example 5
2-methyl-4-(4-oxo-2-phenyl-4 hydrogen-thiochromene-8-yl)-5-oxo-1,4,5)-tetrahydrofuran (THF) (3,4-b)-pyridine-3-carboxylic acid ethyl ester
1.283 kilogram (2.94 moles) 4-acetoxy-3-oxo-1-(4-oxo-2-phenyl-4 hydrogen-thiochromene-8-yl)-1-butylene-2-carboxylic acid, ethyl ester (routine 1b) is suspended in 2.3 liters of ethanol, adds 379.7 gram (2.94 moles) beta-amino butenoic acid ethyls again.Mixture heated 8 hours under reflux temperature.After adding 150 milliliters of saturated hydrochloric acid-ethanolic solns, continue heating 3 hours down in reflux temperature.Mixture is static with crystallization in room temperature.In crystallisate suction strainer to glass frosted funnel, filter flask is with 1.5 liters of boiling alcohol extractions twice behind the suction strainer, and again at 120 ℃, drying is 48 hours in the vacuum drying oven of 1 mmhg.
Productive rate: 990 grams (theoretical value 73%)
Fusing point: 266 ℃ (decomposition)
Claims (4)
1, the preparation method who has the 2-thiochromene fork acetylacetic ester of molecule formula I
Herein: R
1Represent line style or branching type alkyl that 4 carbon atoms are following;
R
2Represent line style or branching type alkyl that 4 carbon atoms are following, it can arbitrarily be replaced by halogen or 7 acetoxyl groups below the carbon atom.
It is characterized in that with Schiff's base with molecular formula (II)
Herein: R
3Represent line style or branching type alkyl and acetylacetic ester reaction that 6 carbon atoms are following with molecule formula III
Herein: R
1, R
2Meaning is the same.
Reaction is preferably under organic inert diluent and the acylating agent existence to be carried out.
2, the compound that makes in accordance with the method for claim 1 with molecule formula I,
Herein: R
1Represent line style or branching type alkyl that 4 carbon atoms are following
R
2Represent line style or branching type alkyl that 4 carbon atoms are following, or brooethyl, chloromethyl, acetoxy-methyl, benzoyloxy group methyl.
3,, be characterised in that to be reflected under the 0-200 ℃ of temperature and carry out according to claim 1 and 2 described methods.
4,, be characterised in that to be reflected under the 10-150 ℃ of temperature and carry out according to claim 1 and 2 described methods.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853517950 DE3517950A1 (en) | 1985-05-18 | 1985-05-18 | Process for the preparation of 2-thiochromenylideneacetoacetic esters |
| DEP3517950.3 | 1985-05-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN86103229A true CN86103229A (en) | 1986-11-19 |
Family
ID=6271079
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN198686103229A Pending CN86103229A (en) | 1985-05-18 | 1986-05-09 | The preparation method of 2-thiochromene fork acetylacetic ester |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS61268679A (en) |
| KR (1) | KR860009006A (en) |
| CN (1) | CN86103229A (en) |
| DE (1) | DE3517950A1 (en) |
| DK (1) | DK229986A (en) |
| ES (1) | ES8706663A1 (en) |
| FI (1) | FI862043A (en) |
| GR (1) | GR861285B (en) |
| HU (1) | HUT43579A (en) |
| NO (1) | NO861804L (en) |
| PT (1) | PT82607B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5116954A (en) * | 1988-04-06 | 1992-05-26 | Lipha, Lyonnaise Industrielle Pharmaceutique | Pharmaceutically useful flavonoic compounds containing at least one substituent on the benzopyranone ring moiety |
| IL89840A (en) * | 1988-04-06 | 1996-10-31 | Lipha | Substituted flavonoid compounds and salts thereof their preparation and pharmaceutical composition containing them |
-
1985
- 1985-05-18 DE DE19853517950 patent/DE3517950A1/en not_active Withdrawn
-
1986
- 1986-05-06 NO NO861804A patent/NO861804L/en unknown
- 1986-05-09 CN CN198686103229A patent/CN86103229A/en active Pending
- 1986-05-15 JP JP61109715A patent/JPS61268679A/en active Pending
- 1986-05-15 FI FI862043A patent/FI862043A/en not_active Application Discontinuation
- 1986-05-16 PT PT82607A patent/PT82607B/en unknown
- 1986-05-16 HU HU862084A patent/HUT43579A/en unknown
- 1986-05-16 ES ES555029A patent/ES8706663A1/en not_active Expired
- 1986-05-16 DK DK229986A patent/DK229986A/en not_active Application Discontinuation
- 1986-05-16 GR GR861285A patent/GR861285B/en unknown
- 1986-05-17 KR KR1019860003845A patent/KR860009006A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DK229986A (en) | 1986-11-19 |
| GR861285B (en) | 1986-09-16 |
| FI862043A0 (en) | 1986-05-15 |
| DE3517950A1 (en) | 1986-11-20 |
| JPS61268679A (en) | 1986-11-28 |
| ES8706663A1 (en) | 1987-07-01 |
| NO861804L (en) | 1986-11-19 |
| PT82607B (en) | 1988-04-22 |
| PT82607A (en) | 1986-06-01 |
| ES555029A0 (en) | 1987-07-01 |
| DK229986D0 (en) | 1986-05-16 |
| HUT43579A (en) | 1987-11-30 |
| FI862043A (en) | 1986-11-19 |
| KR860009006A (en) | 1986-12-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0044228B1 (en) | Heparine esters for use in the manufacture of medicines, and processes for their preparation | |
| CN1861596A (en) | Process for synthesizing antithrombin inhibitor of non-asymmetric non-peptide kind | |
| CN1030076A (en) | The improved preparation of the indolinone derivative that replaces | |
| CN86103229A (en) | The preparation method of 2-thiochromene fork acetylacetic ester | |
| CN1203059C (en) | Novel processes for preparing torsemide intermediate | |
| CN1019911C (en) | Benzoxazine derivative and processes for preparing same | |
| CN1056686A (en) | Improving one's methods of the indolone derivatives that preparation replaces | |
| CN88102448A (en) | Novel nitrogenous compound | |
| CN1019010B (en) | Process for preparing substituted beta-diketones | |
| CN86101794A (en) | The preparation of the intermediate that contains the weedicide of phosphonate group and make by benzoxazines | |
| CN1143079A (en) | Benzo-iso-thiazolyl substituted amino methyl-benzodipyran | |
| CN1039423A (en) | 2, the preparation method of 2-dehydration-1-(β-D-arabinofuranosyl adenin base) thymus pyrimidine | |
| CN1014992B (en) | Quinazolidione and pyridopyrimidine dione and preparing method | |
| CN1046709C (en) | Palladium catalyzed vinylic substitution reactions with 2-substituted-pyridines | |
| CN114213365A (en) | Synthetic method of empagliflozin intermediate | |
| CN1028523C (en) | Process for preparing carbamates, and intermediates therein | |
| CN1723188A (en) | Process for reductive dehalogenation | |
| CN1488630A (en) | Method for preparing triazole antifungal agent | |
| CN1066658A (en) | The asymmetric synthesis of 3-substituted furanoside compounds | |
| CN1082042C (en) | Method for synthesizing lecdopamine | |
| JPH0327345A (en) | Production of phenetylamines | |
| CN1037902A (en) | 7-/D (-)-alpha-amino group-α-(P-hydroxyphenyl) kharophen/-3-(1,2,3-triazoles-4 (5)-thiomethyl-3-cephem-4-carboxylic acid 1, the halo intermediate in the preparation method of 2-propylene glycol ester and this method | |
| CN1075632A (en) | Alkoxylated phenyl and coumarin derivative and application thereof | |
| CN86103741A (en) | New salt preparation method | |
| CN1040439C (en) | Process for prepn. of 1 beta-ethyl-1 alpha-(hydroxymethyl)-1,2,3,4,6,7,12, 12 beta alpha octahydro-indolo [2,3-alpha] quinolizine and novel intermediates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |