KR800001450B1 - Method for preparing 1, 3, 5-trisubstituted benzene derivative - Google Patents
Method for preparing 1, 3, 5-trisubstituted benzene derivative Download PDFInfo
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- KR800001450B1 KR800001450B1 KR7501544A KR750001544A KR800001450B1 KR 800001450 B1 KR800001450 B1 KR 800001450B1 KR 7501544 A KR7501544 A KR 7501544A KR 750001544 A KR750001544 A KR 750001544A KR 800001450 B1 KR800001450 B1 KR 800001450B1
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- KR
- South Korea
- Prior art keywords
- compound
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- general formula
- alkyl group
- benzene derivative
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 6
- -1 1, 3, 5-trisubstituted benzene Chemical class 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 150000001555 benzenes Chemical group 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical class CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- QIZWVJCSCSKKKA-UHFFFAOYSA-N n-hydroxy-2-(3-methoxy-5-methylphenyl)acetamide Chemical compound COC1=CC(C)=CC(CC(=O)NO)=C1 QIZWVJCSCSKKKA-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
내용 없음.No content.
Description
본 발명은 소염, 진통제로서 유용한 신규 화합물인 1,3,5-트리치환 벤젠 유도체(Ⅰ)의 제조방법에 관한 것이다.The present invention relates to a method for preparing 1,3,5-trisubstituted benzene derivative (I) which is a novel compound useful as an anti-inflammatory and analgesic agent.
특히 본 발명은 일반식In particular, the present invention is a general formula
(식중 R1은 저급 알킬기, 사이클로 헥실기, 혹은 비치환 또는 알킬기나 할로겐으로 치환된 페닐기이고; R2는 수소 또는 C1-C5의 저급 알킬기를 나타내고 ; R3는 저급 알킬기임)로 표시된 화합물을 하이드록실아민과 반응시킴을 특징으로 하는 일반식Wherein R 1 is a lower alkyl group, a cyclohexyl group, or an unsubstituted or phenyl group substituted with an alkyl or halogen; R 2 represents hydrogen or a lower alkyl group of C 1 -C 5 ; R 3 is a lower alkyl group. A general formula characterized by reacting a compound with hydroxylamine
(식중 R1,R2는 전기한 바와 동일)로 표시된 1,3,5-트리치환 벤젠 유도체의 제조방법이다.(Wherein R 1 and R 2 are the same as those described above).
본 발명의 방법은 적당하기로는 알코올 용매 중에서, 나트륨 알콕사이드의 존재하에 하이드록실아민 염산염과 일반식(Ⅱ)의 화합물을 반응시킴으로서 행한다.The method of the present invention is preferably carried out by reacting a hydroxylamine hydrochloride with a compound of the general formula (II) in an alcohol solvent in the presence of sodium alkoxide.
본 발명의 화합물(Ⅰ)은, 원료 화합물인 일반식(Ⅱ)의 화합물을 합성하기 곤란하기 때문에 미지인채 그대로 방치되어진 화합물이다.The compound (I) of the present invention is a compound that is left as it is because it is difficult to synthesize a compound of the general formula (II) which is a raw material compound.
일반식(Ⅱ)의 화합물, 즉 본 발명의 원료 화합물은 벤젠 헥상 서로 메타-위치의 관계에 치환기를 배열한 특징있는 구조를 가지는 화합물이다. 일반적으로, 일반식(Ⅱ)를 포함하여 서로 메타-위치에 치환한 벤젠 유도체는 외관상 구조가 단순한 반면에 오늘날까지 알려진 유기화학적 수법으로 조합시켜 선택적으로 합성함은 곤란하며, 따라서 공업적으로 거의 불가능하였다. 본인들은 먼저 출원한 벤젠핵을 합성하는 방법, 즉 비 방향족 화합물에 미리 서로 메타-위치에 치환기를 넣은 다음, 벤젠핵을 만드는 방법(특원소 47-36,773호로 출원 중)을 개발하여 이것에 본 발명의 방법을 조합시킴으로서 일반식(Ⅰ)의 화합물을 간편하게 합성하는데 성공하고, 본 발명을 완성하였다. 방향화 반응, 즉 일반식(Ⅱ)의 화합물의 합성을 반응식으로 표시하면 다음과 같다.The compound of the general formula (II), that is, the raw material compound of the present invention is a compound having a characteristic structure in which substituents are arranged in a meta-position relationship between benzene hexanes. In general, the benzene derivatives substituted in the meta-position with each other, including the general formula (II), have a simple structure but are difficult to selectively synthesize by combining with organic chemical techniques known to date, and thus are almost impossible industrially. It was. They have developed a method for synthesizing a benzene nucleus, that is, putting a substituent in a meta-position to a non-aromatic compound in advance, and then making a benzene nucleus (patent no. 47-36,773). By combining the methods of, the compound of the general formula (I) was successfully synthesized, and the present invention was completed. Aromatization reaction, that is, the synthesis of the compound of general formula (II) is represented by the reaction scheme as follows.
본 발명에서 얻은 화합물은 우수한 소염, 진통작용을 가지고 독성도 낮으며, 치료상 매우 가치있는 것이다.The compound obtained in the present invention has excellent anti-inflammatory, analgesic effect, low toxicity, and is very valuable for treatment.
표 1에 약리 시험의 일례를 나타낸다.Table 1 shows an example of a pharmacological test.
[제1표][Table 1]
이하 실시예에 의해 발명을 설명한다.The invention is illustrated by the following examples.
[실시예 1]Example 1
3-메톡시-5-메틸-페닐아세토 히드록삼산의 제법Preparation of 3-methoxy-5-methyl-phenylaceto hydroxamic acid
에탄올 100㎖에 금속나트륨 5.6g(0.24몰)을 용해시켜 20-25℃로 하이드록실아민 염산염 16g을 가한다. 20분간 교반하고, 메틸 3-메톡시-5-메틸페닐 아세테이트 11.25g(0.058몰)을 20분간 걸쳐서 적하한다. 20-25℃로 30분간 교반 후 40분간 환류한다. 감압하 에탄올을 유거하고 잔사에 빙수 50㎖를 가하여 용해하고, 에테르로 세척 후 초산으로 산성이 되게 한다. 석출한 결정을 여취하여 수세 후 건조하여 조결정 6.0g을 얻었다. 함수 에탄올로 재결정하여 53g의 백색 결정을 얻었다. 융점 119-121℃(분해)Dissolve 5.6 g (0.24 mol) of metallic sodium in 100 ml of ethanol and add 16 g of hydroxylamine hydrochloride at 20-25 ° C. It is stirred for 20 minutes, and 11.25 g (0.058 mol) of methyl 3-methoxy-5-methylphenyl acetate is dripped over 20 minutes. Stir at 20-25 ° C. for 30 minutes and reflux for 40 minutes. Ethanol was distilled off under reduced pressure, and 50 ml of ice water was added to the residue to dissolve. The mixture was washed with ether and acidified with acetic acid. Precipitated crystals were filtered off, washed with water and dried to obtain 6.0 g of crude crystals. Recrystallization with brine ethanol afforded 53 g of white crystals. Melting Point 119-121 ° C (Decomposition)
원소분석치 : C10H13O3NElemental Analysis Value: C 10 H 13 O 3 N
C H NC H N
계산치 61.52 6.71 7.18Calculated 61.52 6.71 7.18
실험치 61.64 6.84 7.30Found 61.64 6.84 7.30
이와 같은 방법으로 실시예 2-8의 화합물이 제조된다.In this manner, the compound of Example 2-8 is prepared.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR7501544A KR800001450B1 (en) | 1975-07-15 | 1975-07-15 | Method for preparing 1, 3, 5-trisubstituted benzene derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR7501544A KR800001450B1 (en) | 1975-07-15 | 1975-07-15 | Method for preparing 1, 3, 5-trisubstituted benzene derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR800001450B1 true KR800001450B1 (en) | 1980-12-10 |
Family
ID=19201317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR7501544A Expired KR800001450B1 (en) | 1975-07-15 | 1975-07-15 | Method for preparing 1, 3, 5-trisubstituted benzene derivative |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR800001450B1 (en) |
-
1975
- 1975-07-15 KR KR7501544A patent/KR800001450B1/en not_active Expired
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