KR830001100B1 - Method for preparing 4-substituted 1, 2-diphenyl-3, 5-dioxopyrazolidine - Google Patents
Method for preparing 4-substituted 1, 2-diphenyl-3, 5-dioxopyrazolidine Download PDFInfo
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- KR830001100B1 KR830001100B1 KR1019790001150A KR790001150A KR830001100B1 KR 830001100 B1 KR830001100 B1 KR 830001100B1 KR 1019790001150 A KR1019790001150 A KR 1019790001150A KR 790001150 A KR790001150 A KR 790001150A KR 830001100 B1 KR830001100 B1 KR 830001100B1
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- diphenyl
- dioxopyrazolidine
- phenyl
- mol
- compound
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- -1 4-substituted 1, 2-diphenyl-3, 5-dioxopyrazolidine Chemical class 0.000 title description 12
- 238000000034 method Methods 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- XDPKQGKEOCYMQC-UHFFFAOYSA-N 1,2-diphenylpyrazolidine-3,5-dione Chemical class O=C1CC(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 XDPKQGKEOCYMQC-UHFFFAOYSA-N 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 229910052799 carbon Inorganic materials 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- 238000000921 elemental analysis Methods 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- DOFQFIHKWSHORF-UHFFFAOYSA-N 2-(1,4-dioxan-2-yl)propanedioic acid Chemical compound O1C(COCC1)C(C(=O)O)C(=O)O DOFQFIHKWSHORF-UHFFFAOYSA-N 0.000 description 2
- SJVNYRBKEVDFEO-UHFFFAOYSA-N 4-(1,4-dioxan-2-yl)-1,2-diphenylpyrazolidine-3,5-dione Chemical compound C1OCC(OC1)C1C(N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1)=O SJVNYRBKEVDFEO-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- KZQDKDRMSDVWEY-UHFFFAOYSA-N C1=CC=CC=C1[PH2](C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound C1=CC=CC=C1[PH2](C=1C=CC=CC=1)C1=CC=CC=C1 KZQDKDRMSDVWEY-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- ZPPTWYWUNQNLAM-UHFFFAOYSA-N diethyl 2-(1,4-dioxan-2-yl)propanedioate Chemical compound C1OCC(OC1)C(C(=O)OCC)C(=O)OCC ZPPTWYWUNQNLAM-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 2
- IEZAAUINNKLRRA-UHFFFAOYSA-N sodium;methylsulfinylmethanolate Chemical compound [Na+].CS(=O)C[O-] IEZAAUINNKLRRA-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- MNLQVRJNUOWTHB-WYMLVPIESA-N (E)-4-(3,5-dioxo-1,2-diphenylpyrazolidin-4-yl)-2-methylbut-2-enoic acid Chemical compound C(=O)(O)/C(=C/CC1C(N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1)=O)/C MNLQVRJNUOWTHB-WYMLVPIESA-N 0.000 description 1
- LIKFNCZLFLCARC-NTUHNPAUSA-N (E)-4-[1-(4-hydroxyphenyl)-3,5-dioxo-2-phenylpyrazolidin-4-yl]-2-methylbut-2-enoic acid Chemical compound C(=O)(O)/C(=C/CC1C(N(N(C1=O)C1=CC=C(C=C1)O)C1=CC=CC=C1)=O)/C LIKFNCZLFLCARC-NTUHNPAUSA-N 0.000 description 1
- MNLQVRJNUOWTHB-OWBHPGMISA-N (Z)-4-(3,5-dioxo-1,2-diphenylpyrazolidin-4-yl)-2-methylbut-2-enoic acid Chemical compound C(=O)(O)\C(=C/CC1C(N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1)=O)\C MNLQVRJNUOWTHB-OWBHPGMISA-N 0.000 description 1
- BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 description 1
- OTVGARFFAAFRAC-UHFFFAOYSA-N 2-bromo-1,4-dioxane Chemical compound BrC1COCCO1 OTVGARFFAAFRAC-UHFFFAOYSA-N 0.000 description 1
- REGFWZVTTFGQOJ-UHFFFAOYSA-N 4,5-dihydro-1,3-thiazol-2-amine Chemical class NC1=NCCS1 REGFWZVTTFGQOJ-UHFFFAOYSA-N 0.000 description 1
- ZFCVUJYWMXKJJA-UHFFFAOYSA-N 4-(2-phenylhydrazinyl)phenol Chemical compound C1=CC(O)=CC=C1NNC1=CC=CC=C1 ZFCVUJYWMXKJJA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZBJJDYGJCNTNTH-UHFFFAOYSA-N Betahistine mesilate Chemical group CS(O)(=O)=O.CS(O)(=O)=O.CNCCC1=CC=CC=N1 ZBJJDYGJCNTNTH-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- WWPOKHWFADPXSS-UHFFFAOYSA-N N(NC1=CC=CC=C1)C1=CC=CC=C1.C(CC(=O)O)(=O)O Chemical compound N(NC1=CC=CC=C1)C1=CC=CC=C1.C(CC(=O)O)(=O)O WWPOKHWFADPXSS-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- PJDHRAUHZGSBHD-UHFFFAOYSA-N [I+].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 Chemical compound [I+].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 PJDHRAUHZGSBHD-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- BEYOBVMPDRKTNR-UHFFFAOYSA-N chembl79759 Chemical compound C1=CC(O)=CC=C1N=NC1=CC=CC=C1 BEYOBVMPDRKTNR-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- PMOWTIHVNWZYFI-WAYWQWQTSA-N cis-2-coumaric acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1O PMOWTIHVNWZYFI-WAYWQWQTSA-N 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- NNQYFBSGBOKZKP-UHFFFAOYSA-N ethylidene(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC)C1=CC=CC=C1 NNQYFBSGBOKZKP-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940101532 meted Drugs 0.000 description 1
- LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
Classifications
-
- 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
- C07D231/14—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 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
- C07D231/28—Two oxygen or sulfur atoms
- C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
- C07D231/32—Oxygen atoms
- C07D231/34—Oxygen atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
내용 없음.No content.
Description
본 발명은 다음 구조식의 4-치환 1,2-디페닐-3,5-디옥소 피라졸리딘의 제조방법에 관한 것이다.The present invention relates to a method for preparing 4-substituted 1,2-diphenyl-3,5-dioxopyrazolidine of the following structural formula.
여기서 R과 R'은 서로 같거나 또는 다르고 수소원자, 저급알킬기, 페닐 또는 -COOR"기(여기서 R"은 수소 또는 저급알킬기)이고 A는 수소원자 또는 하이드록실기. 일반구조식(Ⅰ)의 화합물은 소위 Z-형 또는 E-형 이성체로서 존재하며 위의 일반구조식에 포함된다(또는 그의 혼합물).Wherein R and R 'are the same or different from each other and are a hydrogen atom, a lower alkyl group, a phenyl or -COOR "group where R" is hydrogen or a lower alkyl group and A is a hydrogen atom or a hydroxyl group. The compounds of the general formula (I) exist as so-called Z- or E-type isomers and are included in the above general formula (or mixtures thereof).
영국특허 1 301 857로부터 이미 일반구조식(Ⅰ)의 화합물은 부타졸리딘보다 주작용및 부작용의 해소에 관한한 우수한 소염진통제제로 알려져있다-구조식은 유사-. 다음에 이들 화합물의 제조방법이 수개 기술되어 있다.Already from British Patent 1 301 857 a compound of general structure (I) is known to be an anti-inflammatory analgesic agent superior to butazolidine as far as the main action and side effects are resolved-the structure is similar. Next, several methods for preparing these compounds are described.
일반구조식(Ⅰ)의 화합물은 다음구조식(Ⅱ)의 사이클로 세미아세탈을 다음 구조식(Ⅲ)의 트리아릴포스포란 유도체와 반응시키고 뒤이어 임의로 완화한 루이스산으로 에테르화된 하이드록실기를 유리시키므로서 제조됨을 본 발명에서 알게 되었다.Compounds of the general formula (I) are prepared by reacting a cyclo semiacetal of the following formula (II) with a triarylphosphoran derivative of the following formula (III), followed by liberating hydroxyl groups etherified with an optionally relaxed Lewis acid It has been found in the present invention.
여기서 A'는 수소 또는 에테르화 하이드록실기, 바람직하게는 β-메톡시에톡시메톡시(=MEM)기이다.Wherein A 'is a hydrogen or etherified hydroxyl group, preferably a β-methoxyethoxymethoxy (= MEM) group.
여기서 R와 R'은 위에서와 같고 Ar는 페닐기이다 (임의로 메틸, 메톡시, 또는 페닐과같은 불활성기로 치환됨). 적당한 루이스산으로는 TiCl4및 ZnBr2로 생각될 수 있으나 ZnCl2, ZnJ2, SnCl4, SnBr4, MgBr2및 유사한 메틸할라이드도 좋다.Wherein R and R 'are as above and Ar is a phenyl group (optionally substituted with an inert group such as methyl, methoxy, or phenyl). Suitable Lewis acids may be thought of as TiCl 4 and ZnBr 2, but ZnCl 2, ZnJ 2, SnCl 4 , SnBr 4, MgBr 2 , and may be similar to methyl halide.
화합물(Ⅱ)와 (Ⅲ)의 반응은 디메틸포름 아미드 특히 무수조건하의 디메틸설폭사이드와 같은 아프로틱 용매내에서 수행할 수 있다.The reaction of compounds (II) and (III) can be carried out in an aprotic solvent such as dimethylformamide, especially dimethylsulfoxide under anhydrous conditions.
일반구조식(Ⅱ)의 사이클로 세미아세탈대신에 A가 수소를 나타낼 경우 다음 일반구조식(Ⅱa)의 알데히드가 반응에 사용될 수 있다.When A represents hydrogen instead of cyclo semiacetal of general formula (II), the aldehyde of general formula (IIa) may be used for the reaction.
일반구조식(Ⅲ)의 화합물은 그대로 상응하는 다음 구조식의 포화포스포니움 염으로부터 수소화나트륨, 나트륨아미드, 부릴리튬 또는 페닐리튬과 같은 적당한 금속시약으로 할로겐화 수소를 분리하므로서 제조할 수도 있다.Compounds of general formula (III) may also be prepared by isolating hydrogen halides with a suitable metal reagent such as sodium hydride, sodium amide, burlylithium or phenyllithium from the corresponding saturated phosphonium salts of the following structural formulas.
여기서 R, R' 및 Ar은 위에서와 같고 X(-)은 할로겐 이온이다.Wherein R, R 'and Ar are as above and X (-) is a halogen ion.
반응은 실온에서 교반 후 반응혼합물을 30내지 100℃의 온도에서 바람직하게는 50내지 70℃범위에서 가열하고 그후 냉각하고 다시 실온에서 교반하는 방법으로 진행될 수 있다.The reaction may proceed by stirring the reaction mixture at room temperature and then heating the reaction mixture at a temperature of 30 to 100 ° C., preferably in the range of 50 to 70 ° C., then cooling and again at room temperature.
반응이 완결된 후에 반응 혼합물을 얼음에 붓고 에틸아세테이트 디클로로메탄과 같은 적당한 유기용매로 추출하고, 컬럼-크로마토그라피 또는 염기성, 수용성 매체의 유기용매로 재추출하여 수행한다. 후자의 경우, 생성물은 무기산으로 산성화후(예로 염산)적당한 용매로 추출하여 얻어질 수 있다. 기하(E, Z)이성체의 분리나 그 이상의 정제는 컬럼 크로마토그라피로 얻어질 수 있다.After completion of the reaction, the reaction mixture is poured into ice, extracted with a suitable organic solvent such as ethyl acetate dichloromethane, and re-extracted with column-chromatography or organic solvent in basic, aqueous medium. In the latter case, the product can be obtained by acidification with an inorganic acid (eg hydrochloric acid) and extraction with a suitable solvent. Separation or further purification of geometric (E, Z) isomers can be obtained by column chromatography.
출발물질에서 A가 에테르화된 하이드록실기를 나타내면, 반응 동안 보호된 이 OH기를 유리시켜 A=OH인 구조식(Ⅰ)을 얻는다. 예를들면 이것은 β-메톡시메틸 (MEM)-에텔로 전환된 에테르화된 OH기를 에테르화된 사이클로세미아세탈(Ⅱ)와 완화한 루이스(예 : 디클로로메탄내의 TiCl4) 산과 구조식(Ⅲ)의 트리페닐포스포란과 반응시킨 후 분해는 분해시키는 방법으로 수행될 수 있다.If A represents an etherified hydroxyl group in the starting material, this OH group protected during the reaction is liberated to yield formula (I) with A = OH. For example, this can be attributed to the etherified OH group converted to β-methoxymethyl (MEM) -ether and etherified cyclosemacetal (II) and relaxed Lewis (e.g. TiCl 4 in dichloromethane) After the reaction with triphenylphosphoran, the decomposition can be carried out by a decomposition method.
일반구조식(Ⅱ)의 화합물은 다음 일반구조식(Ⅳ)의 상응하는 사이클릭아세탈을 재배열하는 간단한 방법으로 얻을수 있다.Compounds of the general formula (II) can be obtained by a simple method of rearranging the corresponding cyclic acetals of the general formula (IV).
여기서 A'는 위에서와 같다. 이런 재배열은 예를들면 수용성에탄올에서 가열하는 간단한 방법으로 수행된다.Where A 'is the same as above. This rearrangement is carried out by a simple method, for example by heating in aqueous ethanol.
일반구조식(Ⅳ)의 화합물은 다음 구조식(Ⅴ)의 디에틸-3-(2-에틸렌디옥시에틸) 말로네이트를 하이드라조벤젠상응 에테르화된 p-하이드록시벤젠-β-메톡시에톡시메톡시(=MEM)-에테르와 무수에타놀내의 나트륨용액의 존재에서 반응시켜 얻을 수 있다.The compound of the general formula (IV) is prepared by diethyl-3- (2-ethylenedioxyethyl) malonate of the following formula (V) with hydrazobenzene etherified p-hydroxybenzene-β-methoxyethoxymeth It is obtained by reacting oxy (= MEM) -ether with sodium solution in anhydrous ethanol.
구조식(Ⅴ)의 화합물은 예를들면 2-에틸렌 디옥시에틸브로 마이드를 디에틸말로 네이트로 수소화나트륨 존재하에 벤젠/디메틸포름 아미드 내에서 축합시키는 알려진 방법으로 얻을 수 있다.Compounds of formula (V) can be obtained, for example, by known methods of condensing 2-ethylene dioxyethyl bromide with diethylmalonate in benzene / dimethylformamide in the presence of sodium hydride.
구조식(Ⅱa)의 알데하이드는 A'=수소인 구조식(Ⅳ)의 화합물을 탈케탈화하여 얻을 수 있으며 탈게탈화는 예를들면 보로트리브로 마이드와 무수디클로로메탄내에서 수행된다. 본 발명에 의한 방법은 지정된 위치에 2중결합이 도입되며, 또한 피라졸리딘 환의 C-4위치에서 2 치환된 생성물의 형성이 방지되기 때문에 부산물이 거의 없이 높은 수율로 순조롭게 진행된다.The aldehyde of formula (IIa) can be obtained by deketalizing a compound of formula (IV) wherein A '= hydrogen, and degertalization is carried out, for example, in borotribromide and anhydrous dichloromethane. The process according to the invention proceeds smoothly with high yields with little by-products since double bonds are introduced at the designated positions and also the formation of bisubstituted products at the C-4 position of the pyrazolidine ring is prevented.
다음 실시예는 본 발명의 범위를 제한하지 않고 본 발명을 설명한다.The following examples illustrate the invention without limiting its scope.
[실시예 1]Example 1
p-하이드록시아조벤젠-β-메톡시에톡시메틸에테르(MEM)p-hydroxyazobenzene-β-methoxyethoxymethyl ether (MEM)
테트라하이드로푸란(400㎖)내의 수소화나트륨(무기오일내에 55%분산) 66.14g (1.516몰)의 교반용액에 테트라하이드로푸란 810㎖내의 p-하이드록시아조벤젠용액(191g, 0.963몰)을 적가한다. 15분 동안 교반후, 용액을 냉각시킨다. 그후 0℃에서 MEM-클로라이드(E.J. Corey, J.L. Gras and P. Ulrich, Tetrahedron Lett., 809(1976), 144g(1.156몰)에 적가하고 혼합물을 이 온도에서 30분간 교반한다. 교반은 실온에서 1시간 동안 계속하고 과잉의 수소화나트륨을 물을 가해 분해하고 혼합물을 진공에서 증발한다. 잔류물을 에테르내에 녹이고 물, 5% 수산화 나트륨 및 물로 중성이 될 때까지 차례로 세척한다. 에테르 추출물을 건조하고 감압하 증발한다. 이렇게하여 표제의 화합물을 짙고 붉은 오일로서 형성시키며(271.44g, 98%), 더 정제하지 않고 사용한다.To a stirring solution of 66.14 g (1.516 mol) of sodium hydride (55% dispersion in inorganic oil) in tetrahydrofuran (400 ml) was added dropwise p-hydroxyazobenzene solution (191 g, 0.963 mol) in 810 ml of tetrahydrofuran. After stirring for 15 minutes, the solution is cooled. Then add MEM-chloride (EJ Corey, JL Gras and P. Ulrich, Tetrahedron Lett., 809 (1976), 144 g (1.156 moles)) at 0 ° C. and stir the mixture at this temperature for 30 minutes. Continue for hours and decompose excess sodium hydride by adding water and evaporate the mixture in vacuo, dissolve the residue in ether and wash sequentially with water, 5% sodium hydroxide and water until neutral. This evaporates to form the title compound as a dark red oil (271.44 g, 98%), which is used without further purification.
[실시예 2]Example 2
p-하이드록시하이드라조벤젠에테르p-hydroxyhydrazobenzene ether
에탄올 1300㎖내의 p-하이드록시아조벤젠-MEM-에테르 (220g, 0.768몰)의 용액을 2.2gPd/C 존재하에 실온 및 공기압에서 수소화 한다. 계산된 수소량은 흡수시킨 후, 용액을 여과하고 짙고, 황색의 오일 220g(99%)가 남을 때까지 증발하고 이것을 즉시 다음단계에 사용한다(쉬운 산화능력때문).A solution of p-hydroxyazobenzene-MEM-ether (220 g, 0.768 moles) in 1300 mL of ethanol is hydrogenated at room temperature and air pressure in the presence of 2.2 gPd / C. After the calculated amount of hydrogen is absorbed, the solution is filtered and evaporated until 220 g (99%) of dark, yellow oil is left and immediately used for the next step (because of easy oxidation capacity).
[실시예 3]Example 3
디에틸-2-(2-에틸렌디옥시에틸)-말로네이트Diethyl-2- (2-ethylenedioxyethyl) -malonate
디메틸포름 아미드(1300㎖) 및 벤젠(500㎖)내의 수소화나트륨(무기오일내에 55%분산) 141.38g(3.24몰)의 교반현탁액에 디에틸말로네이트(471.8g, 2.94몰)을 적가한다. 실온에서 H2-생성이 끝날 때까지 교반한후 2-에틸렌디옥시 에틸브로마이드(S.M. Gurvich Zh. Obshch Khim. 27,2888(1957)) (492g, 2.94몰)을 벤젠 500㎖내에 가하고 용액을 80℃에서 16시간 동안 교반한다. 이후, 혼합물을 냉각하고, 과잉의 얼음-물에 붓고 생성물을 에테르로 분리한다. 무수 추출물을 증발시킨 후, 2-(2-에틸렌디옥시에틸)-말로네이트를 얻는다. 비점 105내지 108°(0.5mm)Diethylmalonate (471.8 g, 2.94 moles) was added dropwise to 141.38 g (3.24 moles) of a stirring suspension of dimethylformamide (1300 mL) and sodium hydride (55% dispersion in inorganic oil) in benzene (500 mL). After stirring at room temperature until the completion of H 2 -production, 2-ethylenedioxy ethyl bromide (SM Gurvich Zh. Obshch Khim. 27,2888 (1957)) (492 g, 2.94 moles) was added into 500 ml of benzene and the solution 80 Stir at 16 ° C. The mixture is then cooled, poured into excess ice-water and the product is separated by ether. After evaporation of the anhydrous extract, 2- (2-ethylenedioxyethyl) -malonate is obtained. Boiling Point 105-108 ° (0.5mm)
원소분석 (C11H18O6)Elemental Analysis (C 11 H 18 O 6 )
실험치 : % C 53.42 H 7.42Experimental Value:% C 53.42 H 7.42
이론치 : % C 53.65 H 7.37Theoretic:% C 53.65 H 7.37
[실시예 4]Example 4
4-(2-에틸렌디옥시에틸)-1, 2-디페닐-3, 5-디옥소피라졸리딘4- (2-ethylenedioxyethyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine
하이드라조벤젠(58.4g, 0.317몰)을 교반하면서 무수에탄올 480㎖내의 나트륨 용액(8.02g, 0.348몰)에 가하고 디에틸-2-(2-에틸렌디옥시에틸)-말로네이트(78.05g, 0.317몰)을 2시간 동안 환류온도에서 그속에 가한다. 더 나아가, 혼합물을 1시간 동안 가열하고, 용매를 서서히 증발시켜 건조하고 잔류물을 감압한 1시간 동안 130내지 140℃에서 가열한다. 반응 생성물을 냉각하고, 물에 녹이고, 에테르로 세척하고 활성탄으로 여과한다. 냉각하면서 용액이 산성화한다. 이것으로 백색 고체물질(72.95g, 68%)를 얻고, 오산화인상에서 진공에서 건조하고 더 정제하지 않고 다음 단계에 이용한다. 융점 150℃Hydrazobenzene (58.4 g, 0.317 mol) was added to sodium solution (8.02 g, 0.348 mol) in 480 mL of anhydrous ethanol with stirring and diethyl-2- (2-ethylenedioxyethyl) -malonate (78.05 g, 0.317) Mole) is added thereto at reflux for 2 hours. Furthermore, the mixture is heated for 1 hour, the solvent is evaporated to dryness and the residue is heated at 130 to 140 ° C. for 1 hour under reduced pressure. The reaction product is cooled, dissolved in water, washed with ether and filtered over activated carbon. The solution is acidified with cooling. This gave a white solid (72.95 g, 68%), dried over vacuum on phosphorus pentoxide and used in the next step without further purification. Melting point 150 ℃
원소분석(C19H18N2O4)Elemental Analysis (C 19 H 18 N 2 O 4 )
실험치 : % C 67.71 H 5.33 N 8.23Experimental Value:% C 67.71 H 5.33 N 8.23
이론치 : % 67.44 5.36 8.28Theoretic:% 67.44 5.36 8.28
[실시예 5]Example 5
4-(2-에틸렌디옥시에틸)-1-(p-MEM-옥시페닐-3,5-디옥소-피라졸리딘)4- (2-ethylenedioxyethyl) -1- (p-MEM-oxyphenyl-3,5-dioxo-pyrazolidine)
무수에탄올 140㎖내의 p-하이드록시하이드라조벤젠-MEM-에테르(137g, 0.475몰)를 교반하면서 에탄올(330㎖)내의 나트륨용액(1092g, 0.475몰)에 가한다.P-hydroxyhydroxylazobenzene-MEM-ether (137 g, 0.475 mol) in 140 ml anhydrous ethanol was added to sodium solution (1092 g, 0.475 mol) in ethanol (330 ml) with stirring.
그후 에탄올 120㎖내의 디에틸-2-(2-에틸렌디옥시에틸말로 네이트(117g, 0.475몰)을 환류온도하 2시간 동안 적가한다. 혼합물을 1시간 동안 더 환류하고 용매를 서서히 증발 건조하고 잔류물을 130내지 140℃에서 1시간 동안 감압하가열한다. 반응 생성물을 냉각하고 물에 용해하고 에테르로 세척하고 활성탄상에서 여과한다. 용액을 10%염산으로 PH4까지 산성화하고 분리된 오일을에 틸아세테이트로 추출한다. 이 추출물을 증발 건조하면 오일성 잔류물을 남기고 후자를 아세톤내의 포화된 피페라진 용액에 녹인다. 방치하면 분리되는 4-(2-에틸렌디옥시에틸)-1-(p-MEM-옥시페닐)-3,5-디옥소피라졸리딘의 결정성 피폐라진염을 여과하고 물에 녹인다. 빙초산으로 산성화한 후 생성물을 에테르로 분리한다. 건조된 추출물을 증발시켜 엷은 황색오일로서 원하는 피라졸리딘을 형성시키며 이것은 1, 2, 4, 5-테트라하이드로-1-(p-MEM-옥시페닐)-2-페닐-3H-5-하이드록시-푸로[2,3-C]-피라졸-3-온으로 전환될 수 있는 순수물이다.Then diethyl-2- (2-ethylenedioxyethylmalonate (117 g, 0.475 mol) in 120 mL of ethanol was added dropwise at reflux for 2 hours, the mixture was further refluxed for 1 hour and the solvent was slowly evaporated to dryness and residual The water is heated under reduced pressure for 1 hour at 130 to 140 ° C. The reaction product is cooled, dissolved in water, washed with ether and filtered over activated charcoal The solution is acidified with 10% hydrochloric acid to PH4 and the separated oil is ethyl acetate. The extract is evaporated to dryness, leaving an oily residue and dissolving the latter in a saturated piperazine solution in acetone (4- (2-ethylenedioxyethyl) -1- (p-MEM-oxy) which is separated when left untreated). The crystalline pyrazine salt of phenyl) -3,5-dioxopyrazolidine is filtered and dissolved in water, acidified with glacial acetic acid and the product is separated with ether The dried extract is evaporated to give the desired pyrazole as a pale yellow oil. To form 1, 2, 4, 5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxy-furo [2,3-C] -pyrazole- Pure water that can be converted to 3-on.
[실시예 6]Example 6
1, 2, 4, 5-테트라하이드로-1, 2-디페닐-3H-5-하이드록시-푸로[2, 3-C]-피라졸-3-온1, 2, 4, 5-tetrahydro-1, 2-diphenyl-3H-5-hydroxy-furo [2, 3-C] -pyrazol-3-one
50% 수용성 에탄올 510㎖내의 4-(2-에틸렌디옥시에틸)-1, 2-디페닐-2, 5-디옥소 피라졸리딘(51.36g, 0.152몰)의 용액을 3시간 동안 환류한다. 아직 뜨거운 용액중에서 결정화된 고체물질을 여과로 모으로 진공에서 건조한다.A solution of 4- (2-ethylenedioxyethyl) -1, 2-diphenyl-2, 5-dioxopyrazolidine (51.36 g, 0.152 mol) in 510 ml of 50% aqueous ethanol is refluxed for 3 hours. The solid crystallized in the still hot solution is collected by filtration and dried in vacuo.
1, 2, 4, 5-테트라하이드로-1, 2-디페닐-3H-5-하이드록시-푸로-[2, 3-C]피라졸-3-온 36.66g(82%)을 얻는다.36.66 g (82%) of 1, 2, 4, 5-tetrahydro-1, 2-diphenyl-3H-5-hydroxy-furo- [2, 3-C] pyrazol-3-one are obtained.
융점 : 267°(분해)Melting Point: 267 ° (Decomposition)
원소분석 (C17H14N2O3)Elemental Analysis (C 17 H 14 N 2 O 3 )
실험치 : % C 69.18 H 4.75 N 9.63Experimental Value:% C 69.18 H 4.75 N 9.63
계산치 : % C 69.37 H 4.80 N 9.52Calculated Value:% C 69.37 H 4.80 N 9.52
[실시예 7]Example 7
1, 2, 4, 5-테트라하이드로-1-(p-MEM-옥시페닐)-2-페닐-3H-5-하이드록시-푸로[2, 3-C] 피라졸-3-온1, 2, 4, 5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxy-furo [2, 3-C] pyrazol-3-one
75% 에탄올 1200㎖내의 4-(2-에틸렌디옥시에틸)-1-(p-MEM-옥시페닐)-2-페닐-3, 5-디옥소 피라졸리딘 (130g, 0.294몰) 용액을 6시간 동안 환류하고 증발 건조한다. 얻어진 잔류물을 에틸아세테이트로부터 재결정하여 무색결정으로서 1, 2, 4, 5-테트라하이드로-1-(p-MEM-옥시페닐)-2-페닐-3H-5-하이드록시-푸로[2,3-C]-피라졸-3-온을 얻는다.A solution of 4- (2-ethylenedioxyethyl) -1- (p-MEM-oxyphenyl) -2-phenyl-3,5-dioxopyrazolidine (130 g, 0.294 mol) in 1200 ml of 75% ethanol was added to 6 Reflux over time and evaporate to dryness. The obtained residue was recrystallized from ethyl acetate to give 1, 2, 4, 5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxy-furo [2,3 as colorless crystals. -C] -pyrazol-3-one.
융점 : 203℃ 분해Melting Point: 203 ℃ Decomposition
원소분석 (C21H22N2O6)Elemental Analysis (C 21 H 22 N 2 O 6 )
실험치 : % C 62.99 H 5.49 N 6.95Experimental Value:% C 62.99 H 5.49 N 6.95
이론치 : % 63.31 5.57 7.03Theoretic:% 63.31 5.57 7.03
[실시예 8]Example 8
4-(2-포밀메틸)-1, 2-디페-2, 5-닐디옥소피라졸리딘4- (2-formylmethyl) -1, 2-dipe-2, 5-yldioxopyrazolidine
디클로로메탄 400㎖내의 4-(2-에틸렌디옥시에틸)-1, 2-디페닐-3, 5-디옥소 피라졸리딘(2.54g, 7.5미리몰)용액에 교반하면서 -70℃에서 디클로로메탄 50㎖내의 보로트리브로마이드(18.79g, 75미리몰)의 용액을 가한다. 이 온도에서 교반을 24시간 동안 계속하고 온도를 실온까지 올리고 혼합물을의 과잉의 얼음-물에붓는다.Dichloromethane at -70 ° C with stirring in 4- (2-ethylenedioxyethyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine (2.54 g, 7.5 mmol) solution in 400 ml of dichloromethane A solution of borotribromide (18.79 g, 75 mmol) in 50 ml is added. Stirring at this temperature is continued for 24 hours and the temperature is raised to room temperature and the mixture is poured into excess ice-water.
유기층을 분리하고 중성이 될 때까지 세척하고 (NaHCO3용액) 건조하고(MgSO4)증발 건조한다.The organic layer is separated, washed until neutral (NaHCO 3 solution), dried (MgSO 4 ) and evaporated to dryness.
점성 잔류물을 에틸에테르-디클로로 메탄(8 : 2)로부터 결정하여 원하는 피라졸리딘을 무색고체로서 0.7g (31.7%)을 얻는다.The viscous residue is determined from ethylether-dichloromethane (8: 2) to give 0.7 g (31.7%) of the desired pyrazolidine as a colorless solid.
융점 : 240내지 242℃,Melting Point: 240 ~ 242 ℃,
원소분석 (C17H14N2O3)Elemental Analysis (C 17 H 14 N 2 O 3 )
실험치 : % C 69.54 H 4.92 N 9.44Experimental Value:% C 69.54 H 4.92 N 9.44
이론치 : % 69.37 4.80 9.52Theoretic:% 69.37 4.80 9.52
[실시예 9]Example 9
4-(3-메틸-2-부테닐)-1, 2-디페닐-2, 5-디옥소피라졸리딘4- (3-methyl-2-butenyl) -1, 2-diphenyl-2, 5-dioxopyrazolidine
디메틸설폭사이드 180㎖내의 이소푸로필-트리페닐포스포니움요오드(45.24g, 0.1몰) [G. Witlig and D. Wittenberg, Ann. 606, 1(1977)]을 20내지 25℃에서 나트륨 메틸설피닐 메티드의 교반 현탁액에 적가한다. (R. Greenwald, M. Chaykovsky and E.J. Corey. J. Org Chem., 28, 1128(1963)). 이것은 무기 오일내에 수소화나트륨 55% 분산액의 4.15g(0.095몰) 및 디메틸설폭사이드 120㎖에서 부터 그대로 제조된다. 이 혼합물을 실온에서 30분 동안 교반하고 1, 2, 4, 5-테트라하이드로-1, 2-디페닐-3H-5-하이드록시-푸로[2, 3-C]피라졸-3-온(14g, 0.047몰)을 여러번에 가한다. 혼합물을 실온에서 2시간 동안 교반하고 70℃까지 가온하여 1시간 더 교반한다.Isoprophyl-triphenylphosphonium iodine (45.24 g, 0.1 mole) in 180 ml of dimethyl sulfoxide [G. Witlig and D. Wittenberg, Ann. 606, 1 (1977) is added dropwise to a stirred suspension of sodium methylsulfinyl methide at 20 to 25 ° C. (R. Greenwald, M. Chaykovsky and E. J. Corey. J. Org Chem., 28, 1128 (1963)). It is prepared as is from 4.15 g (0.095 mol) of sodium hydride 55% dispersion and 120 ml of dimethylsulfoxide in inorganic oil. The mixture is stirred at room temperature for 30 minutes and is treated with 1, 2, 4, 5-tetrahydro-1, 2-diphenyl-3H-5-hydroxy-furo [2, 3-C] pyrazol-3-one ( 14 g, 0.047 mol) is added at several times. The mixture is stirred at rt for 2 h, warmed to 70 ° C. and stirred for 1 h more.
16시간 동안 실온에서 교반 후, 반응 혼합물을 과잉의 물에 붓고 니클로로 메탄으로 추출한다. 유기 층을 분리하고, 물로 세척하고, MgSO4상에서 건조하고 증발 건조한다. 얻어진 잔류물을 벤젠에 녹이고 실리카겔 컬럼에 흡수시킨다. 벤젠내에서 10% 아세톤으로 용출하여 원하는 피라졸리딘을무색고체로서 8.79g(58.4%)을 얻는다.After stirring at room temperature for 16 hours, the reaction mixture is poured into excess water and extracted with nichloromethane. The organic layer is separated, washed with water, dried over MgSO 4 and evaporated to dryness. The residue obtained is taken up in benzene and taken up in a silica gel column. Elution with 10% acetone in benzene yields 8.79 g (58.4%) of the desired pyrazolidine as a colorless solid.
융점 : 155내지 157℃Melting Point: 155-157 ℃
원소분석 (C20H20N2O2)Elemental Analysis (C 20 H 20 N 2 O 2 )
실험치 : % C 75.20 H 6.23 N 8.64Experimental Value:% C 75.20 H 6.23 N 8.64
이론치 : % 74.98 6.29 8.74Theoretic:% 74.98 6.29 8.74
[실시예 10]Example 10
4-(2-푸로페닐)-1, 2-디페닐-3, 5-디옥소 피라졸리딘4- (2-furophenyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine
이 화합물은 실시예 9에서와 같은 방법으로 1, 2, 4, 5-테트라하이드로-1, 2-디페닐-3H -5-하이드록시-푸로[2, 3-C]-피라졸-3-온 (5.88g, 0.02몰)과 메틸트리페닐포스포니움요오드[C.H. Collins and G.S. Hammond, J. Org. Chem., 25, 1434(1960)] (17.78g, 0.044몰)에서 출발하고, 디메틸설폭사이드내의 나트륨 메틸 설피닐 메티드(0.04몰) (위에서와 같이 제조된)을 사용하여 제조된다. 표제의 화합물은 실리카겔상(벤젠내 10% 아세톤)에서 컬럼크로마토그라피한 후 무색고체(64.5%)로서 얻어진다.This compound was prepared in the same manner as in Example 9, 1, 2, 4, 5-tetrahydro-1, 2-diphenyl-3H-5-hydroxy-furo [2, 3-C] -pyrazole-3- On (5.88 g, 0.02 mole) and methyltriphenylphosphonium iodine [CH Collins and G.S. Hammond, J. Org. Chem., 25, 1434 (1960)] (17.78 g, 0.044 mole) and prepared using sodium methyl sulfinyl methoxide (0.04 mole) (prepared as above) in dimethylsulfoxide. The title compound is obtained as colorless solid (64.5%) after column chromatography on silica gel (10% acetone in benzene).
융점 : 133내지 135℃(EtOH 95%)Melting Point: 133 ~ 135 ℃ (EtOH 95%)
원소분석 (C18H16N2O2)Elemental Analysis (C 18 H 16 N 2 O 2 )
실험치 : % C 74.14 H 5.63 N 9.37Experimental Value:% C 74.14 H 5.63 N 9.37
이론치 : % 73.95 5.52 9.58Theoretic:% 73.95 5.52 9.58
[실시예 11]Example 11
(E, Z)-4-(2-부테닐)-1, 2-디페닐-3, 5-디옥소 피라졸리딘(E, Z) -4- (2-butenyl) -1, 2-diphenyl-3, 5-dioxo pyrazolidine
이 화합물은 실시예 9에서와 같이 1, 2, 4, 5-테트라하이드로-1, 2-디페닐-3H-5-하이드록시-푸로-[2, 3-C]-피라졸-3-온 (5.88g, 0.02몰)과 에틸트리페닐포스폰 브로마이드(16.33g, 0.044몰) [G. Wittig and D. Wittenberg Ann., 606, 1(1957)]로부터 출발하고, 위와같이 제조한 디메틸 설폭사이드내의 나트륨 메틸설피닐 메티드(0.04몰)을 사용하여 제조한다. 이 화합물은 실리카겔상에서 컬럼크로마토그라피(벤젠내의 10% 아세톤) 한후 E-및 Z-형의 혼합물, 여기서 Z-이성체가 주산물(60%), 이 얻어진다. 융점 167℃ (EtOH/H2O1 : 1) 문헌 융점 128℃인 화합물은 통상의 말로네이트-하이드라조벤젠 법으로 얻어진다.This compound was prepared as 1, 2, 4, 5-tetrahydro-1, 2-diphenyl-3H-5-hydroxy-furo- [2, 3-C] -pyrazol-3-one as in Example 9. (5.88 g, 0.02 mole) and ethyltriphenylphosphon bromide (16.33 g, 0.044 mole) [G. Wittig and D. Wittenberg Ann., 606, 1 (1957), prepared using sodium methylsulfinyl meted (0.04 mol) in dimethyl sulfoxide prepared as above. This compound is subjected to column chromatography on silica gel (10% acetone in benzene), followed by a mixture of E- and Z-forms, where the Z-isomer is the main product (60%). Melting point 167 ° C. (EtOH / H 2 O 1: 1) Document A compound having a melting point of 128 ° C. is obtained by a conventional malonate-hydrazobenzene method.
원소분석 (C19H18N2O2)Elemental Analysis (C 19 H 18 N 2 O 2 )
실험치 : % C 74.32, H 5.87 N 9.22Experimental Value:% C 74.32, H 5.87 N 9.22
이론치 : % C 74.49 H 5.92 N 9.15Theoretic value:% C 74.49 H 5.92 N 9.15
[실시예 12]Example 12
(E, Z)-4-(3-페닐-2-푸로페닐)-1, 2-디페닐-3, 5-디옥소 피라졸리딘(E, Z) -4- (3-phenyl-2-furophenyl) -1, 2-diphenyl-3, 5-dioxo pyrazolidine
이 화합물은 실시예 9에서와 같이 1, 2, 4, 5-테트라하이드로-1, 2-디페닐-3H-5-하이드록시-푸로[2, 3-C]-피라졸-3-온(5.88g, 0.02몰)및 벤질트리페닐포스폰클로라이드(17.11g, 0.044몰)[G. Wittig and M. Schollkopf Chem. Ber. 87, 1318(1954)로부터 출발하고 위와같은 디메틸설폭사이드내의 나트륨 메틸설피닐 메티드(0.04몰)을 사용하여 제조한다. 화합물은 조물질로서 64%수율로 얻어진다.This compound was prepared as 1, 2, 4, 5-tetrahydro-1, 2-diphenyl-3H-5-hydroxy-furo [2, 3-C] -pyrazol-3-one (as in Example 9). 5.88 g, 0.02 mole) and benzyltriphenylphosphonchloride (17.11 g, 0.044 mole) [G. Wittig and M. Schollkopf Chem. Ber. Prepared using 87, 1318 (1954) and sodium methylsulfinyl methoxide (0.04 mol) in dimethyl sulfoxide as above. The compound is obtained as a crude in 64% yield.
Z와 E형은 실리카겔상에서(벤젠내의 10%아세톤) 컬럼크로마토그라피하여 분리될 수 있다.Forms Z and E can be separated by column chromatography on silica gel (10% acetone in benzene).
(Z)-이성체 : 융점 124℃(EtOH95°)(Z) -isomer: Melting point 124 ° C (EtOH95 °)
원소분석 (C24H20N2O2)Elemental Analysis (C 24 H 20 N 2 O 2 )
실험치 : % C 78.29 H 5.31 N 7.48Experimental Value:% C 78.29 H 5.31 N 7.48
이론치 : % 78.23 5.47 7.60Theoretic:% 78.23 5.47 7.60
(E)-이성체 : 융점 133℃(EtOH95°)(E) -isomer: Melting point 133 ° C (EtOH95 °)
C24H20N2O2: 실험치 : % C 78.42 H 5.54 N 7.46C 24 H 20 N 2 O 2 : Experimental Value:% C 78.42 H 5.54 N 7.46
이론치 : % 78.23 5.47 7.60Theoretic:% 78.23 5.47 7.60
[실시예 13]Example 13
(E, Z)-4-(3-카베톡시-2-부테닐)-1, 2-디페닐-3, 5-디옥소피라졸리딘(E, Z) -4- (3-carbetoxy-2-butenyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine
무수디메틸설폭사이드 400㎖내의
**O. Isler. Helv. Chim. Acta, 40, 1241(1957)** O. Isler. Helv. Chim. Acta, 40, 1241 (1957)
원소분석 (C22H22N2O4)Elemental Analysis (C 22 H 22 N 2 O 4 )
실험치 : % C 69.59 H 5.97 N 17.02Experimental Value:% C 69.59 H 5.97 N 17.02
이론치 : % 69.82 5.86 16.91Theoretic:% 69.82 5.86 16.91
같은 용매로 더 용출하여 2개의 이성체로 구성된 중간분획물을 얻고 그후 (E)-형의 분획물 14g(42%)를 무색고체로서 얻고 이것을 사이클로헥산으로 재결정한다.Further eluting with the same solvent yielded an intermediate fraction consisting of two isomers, after which 14 g (42%) of (E) -type fraction were obtained as a colorless solid which was recrystallized from cyclohexane.
융점 : 93℃Melting Point: 93 ℃
[실시예 14]Example 14
(E, Z)-4-(3-카베톡시-2-부테닐)-1, 2-디페닐-3, 5-디옥소 피라졸리딘(E, Z) -4- (3-carbetoxy-2-butenyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine
이 화합물은 실시예 13과 같이 12㎖의 디메틸설폭사이드내의
물리-화학적 및 분석 데이타와 E/Z-이성체 비율은 앞서의 실시예에서 얻어진 데이타와 거의 동일하다.The physico-chemical and analytical data and the E / Z-isomer ratio are nearly identical to the data obtained in the previous examples.
[실시예 15]Example 15
(E,Z)-4-(3-카베톡시-2-부테닐)-1-(p-MEM-옥시페닐)-2-페닐-3, 5-디옥소 피라졸리딘(E, Z) -4- (3-carbetoxy-2-butenyl) -1- (p-MEM-oxyphenyl) -2-phenyl-3,5-dioxopyrazolidine
무수디메틸설폭사이드 90㎖내의
[실시예 16]Example 16
(E)-4-(3-카베톡시-2-부테닐)-1-(p-하이드록시페닐)-2-페닐-3,5-디옥소 피라졸리딘(E) -4- (3-carbetoxy-2-butenyl) -1- (p-hydroxyphenyl) -2-phenyl-3,5-dioxopyrazolidine
디클로로메탄 750㎖내의 티타니움 테트라 클로라이드(77.26g, 0.407몰)의 교반용액에 0℃에서 디클로로메탄 400㎖내의 실시예 15에서와 같이 제조한 (E)-4-(3-카베톡시-2-부테닐)-1-(p-MEM-옥시페닐)-2-페닐-3, 5-디옥소 피라졸리딘(3.93g, 0.081몰)의 용액을 적가한다.To a stirred solution of titanium tetrachloride (77.26 g, 0.407 mol) in 750 ml of dichloromethane, prepared as in Example 15 in 400 ml of dichloromethane at 0 ° C., as in Example 15 (E) -4- (3-carbetoxy-2-part A solution of tenyl) -1- (p-MEM-oxyphenyl) -2-phenyl-3, 5-dioxopyrazolidine (3.93 g, 0.081 mol) is added dropwise.
교반을 1시간 동안 계속하고 혼합물을 과잉의 얼음-물에 붓는다. 유기층을 분리하고 오일성 잔류물을 얻고 디클로로메탄내에 녹이고 실리카겔 컬럼상에 흡수시킨다.Stirring is continued for 1 hour and the mixture is poured into excess ice-water. The organic layer is separated and an oily residue is obtained which is taken up in dichloromethane and taken up on a silica gel column.
디클로로메탄내의 10% 메탄올에서 용출하여 무색고체로서 표제화합물의 25.4g(79%)를 얻는다.Elution with 10% methanol in dichloromethane affords 25.4 g (79%) of the title compound as a colorless solid.
융점 : 70내지 74℃Melting Point: 70 ~ 74 ℃
원소분석 (C22H22N2O5)Elemental Analysis (C 22 H 22 N 2 O 5 )
실험치 : % C 66.84 H 5.51 N 6.92Experimental Value:% C 66.84 H 5.51 N 6.92
이론치 : % 66.99 5.62 7.10Theoretic:% 66.99 5.62 7.10
[실시예 17]Example 17
(E)-4-(3-카복시-2-부테닐)-1, 2-디페닐-3, 5-디옥소 피라졸리딘(E) -4- (3-carboxy-2-butenyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine
10% 수산화나트륨 10㎖내의 실시예 13에서와 같이 제조한 (E)-4-(3-카베톡시-2-부테닐)-1, 2-디페닐-3, 5-디옥소 피라졸리딘(2.25g, 5.28몰)을 30분동안 실온에서 교반하고 이후 10% 염산으로 산성화한다. 침전된 생성물을 디클로로메탄으로 분리하고 건조추출물을 증발시킨 후 에틸에테르로부터 재결정하여 점성 잔류물을 얻는다(1.05g, 56.75%).(E) -4- (3-carbetoxy-2-butenyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine prepared as in Example 13 in 10 ml of 10% sodium hydroxide ( 2.25 g, 5.28 mol) is stirred for 30 minutes at room temperature and then acidified with 10% hydrochloric acid. The precipitated product is separated with dichloromethane and the dry extract is evaporated and recrystallized from ethyl ether to give a viscous residue (1.05 g, 56.75%).
융점 : 141℃Melting Point: 141 ℃
원소분석 (C20H18N2O4)Elemental Analysis (C 20 H 18 N 2 O 4 )
실험치 : % C 68.28 H 5.19 N 7.97Experimental Value:% C 68.28 H 5.19 N 7.97
이론치 : % 68.56 5.18 8.00Theoretic:% 68.56 5.18 8.00
[실시예 18]Example 18
(Z)-4-(3-카복시-2-부테닐)-1, 2-디페닐-3, 5-디옥소 피라졸리딘(Z) -4- (3-carboxy-2-butenyl) -1, 2-diphenyl-3, 5-dioxopyrazolidine
이 화합물은 실시예 17에서와 같이, 10% 수산화나트륨(20㎖)과 함께 실시예 13에서와 같이 제조한(Z)-4-(3-카베톡시-2-부테닐)-1, 1-디페닐-3, 5-디옥소 피라졸리딘(1g, 2.6몰)을 가수분해하여 제조한다. 통상의 방법을 진행 후, 화합물을 에틸에테르로 부터 재결정하고 무색결정으로서 원하는 피라졸리딘 0.6g(61%)를 얻는다.This compound was prepared as in Example 13 with 10% sodium hydroxide (20 mL), as in Example 17, (Z) -4- (3-carbetoxy-2-butenyl) -1, 1- Diphenyl-3, 5-dioxopyrazolidine (1 g, 2.6 mol) is prepared by hydrolysis. After the usual method, the compound is recrystallized from ethyl ether to obtain 0.6 g (61%) of the desired pyrazolidine as colorless crystals.
융점 : 65℃Melting Point: 65 ℃
원소분석 (C20H18N2O4)Elemental Analysis (C 20 H 18 N 2 O 4 )
실험치 : % C 68.37 H 5.28 N 7.88Experimental Value:% C 68.37 H 5.28 N 7.88
이론치 : % 68.56 5.28 7.88Theoretic:% 68.56 5.28 7.88
[실시예 19]Example 19
(E)-4-(3-카복시-2-부테닐)-1-(p-하이드록시페닐)-2-페닐-3, 5-디옥소-피라졸 리딘(E) -4- (3-carboxy-2-butenyl) -1- (p-hydroxyphenyl) -2-phenyl-3, 5-dioxo-pyrazole ridine
이 화합물을 같은 방법으로 10% 수산화나트륨(200㎖)과 함께 실시예 16에서와 같이 제조한 (E)-4-(3-카베톡시-2-부테닐)-1-(p-하이드록시페닐)-2-페닐-3, 5-디옥소피라졸리딘(10g, 25m몰)을 가수분해하여 제조한다. 얻어진 화합물을 아세토니트릴로부터 재결정한다.This compound was prepared as in Example 16 with 10% sodium hydroxide (200 mL) in the same manner as (E) -4- (3-carbetoxy-2-butenyl) -1- (p-hydroxyphenyl ) -2-phenyl-3,5-dioxopyrazolidine (10 g, 25 mmol) is prepared by hydrolysis. The obtained compound is recrystallized from acetonitrile.
이것은 무색결정의 표제화합물 2.15g(23.2%)이다.This is 2.15 g (23.2%) of the title compound as colorless crystals.
원소분석 (C20H18N2O5)Elemental Analysis (C 20 H 18 N 2 O 5 )
실험치 : % C 65.30 H 5.01 N 7.61Experimental Value:% C 65.30 H 5.01 N 7.61
이론치 : % 65.56 4.95 7.66Theoretic:% 65.56 4.95 7.66
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019790001150A KR830001100B1 (en) | 1979-04-12 | 1979-04-12 | Method for preparing 4-substituted 1, 2-diphenyl-3, 5-dioxopyrazolidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019790001150A KR830001100B1 (en) | 1979-04-12 | 1979-04-12 | Method for preparing 4-substituted 1, 2-diphenyl-3, 5-dioxopyrazolidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR830001100B1 true KR830001100B1 (en) | 1983-06-11 |
Family
ID=19211355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019790001150A KR830001100B1 (en) | 1979-04-12 | 1979-04-12 | Method for preparing 4-substituted 1, 2-diphenyl-3, 5-dioxopyrazolidine |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR830001100B1 (en) |
-
1979
- 1979-04-12 KR KR1019790001150A patent/KR830001100B1/en active
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