Pyrido[2,3-b]pyrazine 유도체의 합성 (제1보)

김호식,김광식,여윤희,Kim, Ho-Sik,Kim, Kwang-Sik,Yeo, Yun-Hee 대한화학회 2005 대한화학회지 Vol.49 No.6

새로운 Quinoxaline류의 합성과 토토머화 현상 (제1보)

김호식,김진희,Ho Sik Kim,Jin Hee Kim 대한화학회 2003 대한화학회지 Vol.47 No.3

3-(1-Ethoxycarbonyl)ethyl-1,2-dihydro-2-oxoquinoxaline(8)을 hydrazine hydrate와 반응시켜 3-(1-hydrazinocarbonyl)ethyl-2-hydroxyquinoxaline(9)을 합성하였고, 화합물 9를 치환 벤즈알데하이드류 또는 heteroaryl aldehyde류와 반응시켜 2-hydroxyquinoxaline류(10-12)를 합성하였다. 또한 화합물 9를 alkyl (ethoxymethylene)- cyanoacetate류 또는 ethoxymethylenemalononitrile과 반응시켜 분자내 고리화반응에 의하여 5-amino-1-[2-(3-hydroxyquinoxalin-2-yl)propanoyl]-pyrazole류(13)를 합성하였다. 얻어진 화합물 10-13은 dimethyl sulfoxide 용액에서 lactam형과 lactime형 사이에 토토머화 현상을 나타내었는데, 이들의 토토머 비를 $^1H$ NMR로서 측정하였다. 그리고 합성한 화합물들에 대한 제초력과 살균력도 조사하였다. The reaction of 3-(1-ethoxycarbonyl)ethyl-1,2-dihydro-2-oxoquinoxaline (8) with hydrazine hydrate gave 3-(1-hydrazinocarbonyl)ethyl-2-hydroxyquinoxaline (9). The reaction of compound 9 with substituted benzaldehydes and heteroaryl aldehydes afforded 2-hydroxyquinoxalines (10-12), respectively. The reaction of compound 9 with alkyl (ethoxymethylene)cyanoacetates and ethoxymethylenemalononitrile resulted in the intramolecular cyclization to give the 5-amino-1-[2-(3-hydroxyquinoxalin-2-yl)propanoyl]-pyrazoles (13), respectively. Compounds 10-13 showed the tautomerism between the lactam and lactim forms in dimethyl sulfoxide solution. The tautomer ratios were determined by the $^1H$ NMR. The herbicidal and fungicidal activities of the synthesized compounds were investigated.

새로운 Pyrazolylquinoxaline류의 합성

김호식,곽삼탁,Kim, Ho Sik,Kwag, Sam Tag 대한화학회 2000 대한화학회지 Vol.44 No.3

6-Chloro-2-hydrazinoquinoxaline4-oxide(10)를 아세틸아세톤 또는 디벤조일메탄과 반응시켜 분자내 고리화반응에 의한 6-chloro-2-(3,5-disubstituted pyrazol-1-yl) quinoxaline 4-oxide류(11)를 합성하였다. 화합물 11을 phosphoryl chloride로 염소와 반응시켜 3,6-dichloro-2-(3,5-disubstituted pyrazol-1-yl)quino-xaline류(12)를 합성한 다음 hydrazine hydrate 반응시켜 6-chloro-3-hydrazino-2-(3,5-disubstituted pyrazol-1-yl)quinoxaline류(13)를 합성하였다. 화합물 13을 치환 벤즈알데히드류, benzenesulfonyl chloride, 치환 benzoyl chloride류 및 acyl chlorid 류와 반응시켜 새로운 pyrazolylquinoxaline류(14-17)를 각각 합성하였다. The reaction of 6-chloro-2-hydrazinoquinoxaline 4.oxide(10) with acetylacetone or dibenzoylmethane gave 6-chloro-2-(3,5-disubstituted pyrazol-1-yl)quinoxaline 4-oxides (11) through the intramolecular·cyclization.The chlorination of compound 11 with phosphoryl chloride afforded 3,6-dichloro-2-(3,5-disubstituted pyrazol-1-yl)quinoxalines (12), whose reaction with hydrazine hydrate provided 6-chloro-3-hydrazinodehydes, benzenesulfonyl chloride, substituted benzoyl chlohdes or acyl chlorides gave novel pyrazolylquinoxalines (14-17).

Pyriodo[2,3-b]pyrazine류의 합성과 토토머화 현상

김호식,최경옥,Kim, Ho-Sik,Choi, Kyung-Ok,Kurasawa, Yoshihisa 대한화학회 2000 대한화학회지 Vol.44 No.5

2-Methoxycarbonylmethylene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(5)을 hydrazine hydrate와 ethylenediamine을 반응시켜 2-hydrazinocarbonylmethylene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(6)과 2-aminoethylcarbamoylmethylene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(7)을 각각 합성하였다. 화합물 6 또는 7을 치환 벤즈알데히드류 및 헤테로아릴 알데히드류와 반응시켜 pyrido[2,3-b]pyrazin류(8-13)를 각각 합성하였다. 몇가지 pyrido[2,3-b]pyrazin은 용액에서 enamine형,methylene imine형, methylene imine형,enaminol형 사이에 토토머화 현상을 나타내었는데, 이들의 토토머 비는 1H NMR로서 측정하였다. The reaction of 2-methoxycarlmethylen-l,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(5) with hydrazine hydrate and ethylenediamine gave 2-hydrazinocarbonylmethylene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(6) and 2-aminoethylcarbamethylene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(7), res-pectively. The reaction of compound 6 or 7 with substituted benzaldehydes or heteroaryl aldehydes afforded pyrido[2,3-b]pyrazines(8-13). Some pyrin the enamine, methylene imine and enaminol forms in solution. The tau-tomer ratios were determined by the H NMR.

새로운 1,2,4-Triazole 유도체의 합성에 관한 연구

김호식,박태주,도이향,이만길,창택가구,Kim, Ho Sik,Park Tae Joo,Doh Yi Hyang,Lee Man Kil,Kurasawa Yoshihisa 대한화학회 1992 대한화학회지 Vol.36 No.5

${\circo}-페닐렌디아민(3)을 출발물질로 하여 4단계를 거쳐 {\alpha}-arylhydrazonoacylazide(7)를 합성하였다. 얻어진 {\alpha}-arylhydrazonoacylazide(7)는 디메틸슬폭시드 용액에서 hydrazone imine형과 diazenyl enamine형으로 존재하는데 이들 사이의 토오토메리 현상을 ^1H-NMR 스펙트럼 데이타에 의하여 측정된 토오토머 비로서 고찰하였다. {\alpha}-arylhydrazonoacylazide(7)를 벤젠용매에서 환류시켜 1-aryl-3-quinoxalinyl-1,2,4-triazol(8)을 합성하였다.$ ${\alpha}-Arylhydrazonoacylazide(7) was synthesized starting from {\circo}-phenylenediamine(3) in four steps. The tautomeric behavior of {\alpha}-arylhydrazonoacylazide(7) between the hydrazone imine and diazenyl enamine forms in the dimethyl sulfoxide solution was investigated on the basis of the tautomer ratio determined by the ^1H-NMR spectral data. The 1-aryl-3-quinoxalinyl-1,2,4-triazol(8) was synthesized from {\alpha}-arylhydrazonoacylazide(7) by refluxing in benzene.$

Quinoxaline 고리를 가진 Pyrazole류 및 N-Phenylethanamide류의 합성과 토토머화 현상

김호식,최경옥,이형철,곽삼탁,Kim, Ho Sik,Choi, Kyung Ok,Lee, Hyong Choul,Kwag, Sam Tag,Yoshihisa Kurasawa 대한화학회 2001 대한화학회지 Vol.45 No.5

3-Methoxycarbonylmethylene-2-oxo-1,2,3,4-tetrahydroquinoxaline(7)을 hydrazine hydrate와 반응시켜 3-hydrazinocarbonylmethylene-2-oxo-1,2,3,4-tetrahydroquinoxaline(8)을 합성하였다. 화합물 8을 alkyl (ethoxymethylene)cyanoacetate류와 반응시켜 [(quinoxalin-2-ylidene)ethanoyl]-1H-pyrazole류(9)를 합성하였고, 화합물 9b를 N-alkylaniline류와 반응시켜 N-alkyl-(quinoxalin-2-ylidene)-N-phenylethanamide류(10)를 합성하였다. 얻어진 화합물 9, 10은 용액에서 enamine 형과 methylene imine 형 사이에 토토머화 현상을 나타내었는데, 이들의 토토머비를 $^1H$ NMR 로서 측정하였다. The reaction of 3-methoxycarbonylmethylene-2-oxo-1,2,3,4-tetrahydroquinoxaline(7) with hydrazine hydrate gave 3-hydrazinocarbonylmethylene-2-oxo-1,2,3,4-tetrahydroquinoxaline(8). The reaction of compound 8 with alkyl (ethoxymethylene)cyanoacetates gave the [(quinoxalin-2-ylidene)ethanoyl]-1H-pyra-zoles(9). The reaction of compound 9b with N-alkylanilines provided the N-alkyl-(quinoxalin-2-ylidene)-N-phenylethanamides(10). Compounds 9 and 10 showed the tautomerism between the enamine and methylene imine forms in solution. The tautomer ratios were determined by the $^1H$ NMR.

조영제 사용이 양성자 Range와 SOBP(Spread-Out Bragg peak)에 미치는 영향

김호식,최승오,김은숙,전상민,염두석,Kim, Ho Sik,Choi, Seung Oh,Kim, Eun Sook,Jeon, Sang Min,Youm, Doo Seok 대한방사선치료학회 2014 대한방사선치료학회지 Vol.26 No.2

목 적 : 조영제는 CT모의치료시 정상조직과 악성종양을 구분하는데 뛰어난 대조도를 제공하기 때문에 CT모의치료에 널리 사용하고 있다. 하지만 조영제는 치료계획 CT에서 일시적으로 존재하기 때문에, 치료계획과 실제 치료 사이에는 Hounsfield Unit(HU)의 차이가 발생하게 된다. 이에 본 연구에서는 조영제 사용으로 인한 HU의 변화가 양성자 치료계획에 미치는 영향을 확인 하고자한다. 대상 및 방법 : 20명의 간암 환자에게서 Phase에 따른 HU값의 변화를 측정하였다, 그리고 5명의 양성자치료계획에서 HU변화에 따른 Range와 Spread-Out Bragg peak(SOBP)의 변화를 살펴보았다. Hand made water phantom을 이용하여 깊이와 HU의 변화에 따른 Range와 SOBP의 변화를 확인하였다. 결 과 : 20명 간암 환자의 HU 변화(Pre contrast, Arterial phase, Porta phase)는 간 조직에서 ($58{\pm}5.7$, $75{\pm}9.5$, $117{\pm}14.6$)이었으며 대동맥에서($40{\pm}6.1$, $279{\pm}49.0$, $154{\pm}22.8$)이었다. 5명의 간암 양성자치료계획에서 HU 변화에 따른 Range 변화는 평균 2.5 mm, SOBP 변화는 평균 1.4 mm 이었다. Hand made water phantom study에서는 HU가 증가함에 따라 Range는 감소되었고 SOBP는 줄어들었다. 결 론 : 양성자 치료계획에서 HU값의 변화는 양성자 Range와 SOBP를 변화시켰다. 실제 양성자 빔에서 HU 변화에 따른 Range와 SOBP의 변화에 대한 추가적인 연구가 필요할 것으로 사료 된다. Purpose : Intravenous contrast medium is a substance used to enhance the contrast of normal tissues or malignant tissues within the body. For this reason, intravenous contrast media have been extensively used form treatment-planning CT. However, when the patient is receiving proton therapy, there is no contrast medium in that moment. In this study, evaluate the influence of intravenous contrast medium on proton range and Spread-Out Bragg peak(SOBP) in Treatment Planning System(TPS). Materials and Methods : Hounsfield Unit(HU) value were measured by 20 liver cancer patients with phase change. and evaluate the proton range and SOBP on 5 liver proton treatment plan. By using the hand made water phantom measure the proton range and SOBP on proton treatment plan with changing HU and Depth. Results : Changing value(Pre contrast, Arterial phase, Portal phase) in liver cancer patient were ($58{\pm}5.7$, $75{\pm}9.5$, $117{\pm}14.6$ for liver tissue) and ($40{\pm}6.1$, $279{\pm}49.0$, $154{\pm}22.8$ for aorta), respectively. The mean difference of range was 2.5mm and SOBP was 1.4mm according to HU change. In phantom study, proton range was shorter and SOBP was narrowed with increasing HU. Conclusion : We verify that HU change lead to range and SOBP change in TPS. Additional study is required to verify that change of HU make range and SOBP be changed in actual substance.

1,3-쌍극성 고리화 첨가반응에 의한 Isoxazolo[2,3-${\alpha}$]quinoxaline류와 Pyrrolo[1,2-${\alpha}$]quinoxaline류의 선택적인 합성

김호식,남순화,Kim Ho Sik,Nam Soon Hwa,Kurasawa Yoshihisa 대한화학회 1990 대한화학회지 Vol.34 No.5

2,6-dichloroquinoxaline (13)과 m-chloroperbenzoic acid를 반응시켜 2,6-dichloroquinoxaline 4-oxide (14)를 합성하고, 이것과 pyrrolidine 혹은 indoline을 반응시켜 2-substituted 6-chloroquinoxaline 4-oxide류(15)를 합성하였다. 그리고 이들과 dimethyl acetylenedicarboxylate를 반응시키니 isoxazolo[2,3-a]quinoxaline류(16)와 pyrrolo[1,2-a]quinoxaline류 (17)가 선택적으로 합성되었다. 더욱이 pyrrolo[1,2-a]quinoxaline류 (17)는 isoxazolo[2,3-a]quinoxaline류 (16)의 고리변환에 의하여 생성된다는 것을 알았다. The reaction of 2,6-dichloroquinoxaline (13) with m-chloroperbenzoic acid gave 2,6-dichloroquinoxaline 4-oxide (14), whose reaction with pyrrolidine or indoline provided 2-substituted 6-chloroquinoxaline 4-oxides (15). The isoxazolo[2,3-a]quinoxalines (16) and pyrrolo[1,2-a]quinoxalines (17) were selectively synthesized from the 2-substituted 6-chloroquinoxaline 4-oxides (15) and dimethyl acetylenedicarboxylate. Moreover, the pyrrolo[1,2-a]quinoxalines (17) were found to be produced by the ring transformation of the isoxazolo[2,3-a]quinoxalines (16).

Pyrazolylquinoxaline류 및 Pyrazolylpyrrolo[1,2-a]-quinoxaline류의 합성

김호식,이성욱,정원영,한성욱,김동일,Kim, Ho Sik,Lee, Seong Uk,Jeong, Won Young,Han, Sung Wook,Kim, Dong Il,Yoshihisa Kurasawa 대한화학회 2001 대한화학회지 Vol.45 No.4

6-Chloro-2-hydrazinoquinoxaline(4) 또는 6-chloro-hydrazinoquinoxaline 4-oxide(7)를 alkyl(ethoxymethylene)cyanoacetate류와 반응시켜 prazolylquinoxaline류(5,8)를 합성하였다. 그리고 화합물 8을 dimethyl acethylenedicarboxylate와 반응시켜 1,3-쌍극성 고 리와 첨가반응과 고리변환에 의하여 pyrazolylpyrrolo[1,2-a]quinoxaline류(9)를 합성하였다. The reaction of 6-chloro-2-hydrazinoquinoxaline(4) or 6-chloro-2-hydrazinoquinoxaline 4-oxide(7) with alkyl (ethoxymethylene)cyanoacetates gave pyrazolylquinoxalines(5, 8). The reaction of compounds 8 with dimethyl acetylenedicarboxylate resulted in the 1,3-dipolar cycloaddition reaction and then ring transformation to afford pyrazolylpyrrolo[1,2-a]quinoxalines(9).

Pyrazolo[3,4-b]quinoxaline 유도체의 합성 (제2보)

김호식,이형철,Kim, Ho-Sik,Lee, Hyung-Chul 대한화학회 2005 대한화학회지 Vol.49 No.4