KR101613065B1 - Synthetic method of dihydroquinoline derivatives - Google Patents

Synthetic method of dihydroquinoline derivatives Download PDF

Info

Publication number
KR101613065B1
KR101613065B1 KR1020140145237A KR20140145237A KR101613065B1 KR 101613065 B1 KR101613065 B1 KR 101613065B1 KR 1020140145237 A KR1020140145237 A KR 1020140145237A KR 20140145237 A KR20140145237 A KR 20140145237A KR 101613065 B1 KR101613065 B1 KR 101613065B1
Authority
KR
South Korea
Prior art keywords
dihydroquinoline
formula
present
aryl group
cdcl
Prior art date
Application number
KR1020140145237A
Other languages
Korean (ko)
Inventor
김대영
Original Assignee
순천향대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 순천향대학교 산학협력단 filed Critical 순천향대학교 산학협력단
Priority to KR1020140145237A priority Critical patent/KR101613065B1/en
Application granted granted Critical
Publication of KR101613065B1 publication Critical patent/KR101613065B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

Disclosed is a synthesis method of a dihydroquinoline derivative. According to the present invention, the synthesis method can efficiently synthesize a dihydroquinoline derivative from allyl alcohol derivatives in presence of an organic catalyst with a high yield in a short amount of time.

Description

다이하이드로퀴놀린 유도체의 제조방법{Synthetic method of dihydroquinoline derivatives}Synthetic method of dihydroquinoline derivatives < RTI ID = 0.0 >

본 발명은 생리활성을 갖는 다이하이드로퀴놀린 유도체를 효율적으로 제조하는 방법에 관한 것으로, 알릴 알코올 유도체(allyl alcohol derivatives)로부터 티오유레아 촉매를 이용하여 다이하이드로퀴놀린 유도체를 제조하는 제조방법에 관한 것이다.The present invention relates to a method for efficiently producing a dihydroquinoline derivative having physiological activity, and more particularly, to a method for producing a dihydroquinoline derivative from allyl alcohol derivatives using a thiourea catalyst.

자연에 존재하는 많은 생리활성분자들은 광학활성을 나타내는 한 가지 이성질체로만 구성된 경우가 많다. 대부분의 생리활성 분자의 경우 한 가지 입체 이성질체만 약리효과를 나타낸다고 알려져 있고, 다른 입체 이성질체는 부작용을 유발할 수 있는 위험성을 지니는 것으로 알려져 있어 한 가지 이성질체만 효과적으로 합성해낼 수 있는 입체선택적인 비대칭 합성방법에 대한 연구는 매우 중요하게 인식되고 있고, 실제로 의약화학분야에서 활발히 진행되고 있다. Many of the physiologically active molecules present in nature are often composed of only one isomer that exhibits optical activity. In the case of most physiologically active molecules, only one stereoisomer is known to exhibit a pharmacological effect, while other stereoisomers are known to have the risk of causing side effects. Thus, a stereoselective asymmetric synthesis method capable of effectively synthesizing only one isomer The research on is very important and it is actively proceeding in the field of medicinal chemistry.

다이하이드로퀴놀린 유도체는 천연물에 널리 존재하는 중요한 구조의 화합물로서, 다양한 의약품의 핵심 골격으로 사용되고 있다.Dihydroquinoline derivatives are important structural compounds widely found in natural products and are used as core skeletons of various medicines.

본 발명에서는 알릴 알코올 유도체(allyl alcohol derivatives)로부터 다이하이드로퀴놀린 유도체를 효율적으로 제조할 수 있다. In the present invention, dihydroquinoline derivatives can be efficiently produced from allyl alcohol derivatives.

본 발명의 목적은 알릴 알코올 유도체로부터 티오유레아를 유기촉매로 이용하여 다이하이드로퀴놀린 유도체를 높은 수율로 효율적으로 제조할 수 있도록 한 다이하이드로퀴놀린 유도체의 제조방법을 제공하는 데 있다.An object of the present invention is to provide a method for producing a dihydroquinoline derivative, which enables efficient production of a dihydroquinoline derivative from an allyl alcohol derivative using thiourea as an organic catalyst at a high yield.

상기 목적을 달성하기 위하여, 본 발명에 따른 다이하이드로퀴놀린 유도체의 제조방법은, 하기 [화학식 1]의 1,3-디페닐티오유레아(1,3-diphenylthiourea) 촉매와 산 촉매 HBr를 이용하여, 하기 [화학식 2]의 구조를 갖는 알릴 알코올 유도체(allyl alcohol derivatives)를 하기 [반응식 1]과 같이 반응시키는 것을 특징으로 한다.In order to accomplish the above object, the present invention provides a process for preparing a dihydroquinoline derivative, which comprises reacting 1,3-diphenylthiourea catalyst and acid catalyst HBr of formula (1) The allyl alcohol derivatives having the structure of the following formula 2 are reacted as shown in Reaction Scheme 1 below.

[반응식 1][Reaction Scheme 1]

Figure 112014102093914-pat00001
Figure 112014102093914-pat00001

상기 [반응식 1]에서 상기 R1은 수소 또는 메틸이다. 상기 R2는 C6-C14의 아릴기이다. 상기 아릴기는 C1-C3의 알콕시기, 알킬기 또는 할로겐으로 치환될 수 있다. 상기 Ts는 토실기(tosyl)이다.In the above Reaction Scheme 1, R 1 is hydrogen or methyl. R 2 is a C 6 -C 14 aryl group. The aryl group may be substituted with a C 1 -C 3 alkoxy group, an alkyl group or a halogen. Ts is a tosyl.

[화학식 1][Chemical Formula 1]

Figure 112014102093914-pat00002
Figure 112014102093914-pat00002

[화학식 2](2)

Figure 112014102093914-pat00003
Figure 112014102093914-pat00003

상기 [화학식 2]에서 상기 R1은 수소 또는 메틸이다. 상기 R2는 C6-C14의 아릴기이다. 상기 아릴기는 C1-C3의 알콕시기, 알킬기 또는 할로겐으로 치환될 수 있다.In the above formula (2), R 1 is hydrogen or methyl. R 2 is a C 6 -C 14 aryl group. The aryl group may be substituted with a C 1 -C 3 alkoxy group, an alkyl group or a halogen.

상술한 바와 같이, 본 발명에 따르면, 간단한 유기 물질인 티오유레아를 유기촉매로 사용하여 알릴 알코올 유도체(allyl alcohol derivatives)로부터 높은 수율의 다이하이드로 퀴놀린 유도체를 효율적으로 제조할 수 있다.As described above, according to the present invention, a dihydroquinoline derivative having a high yield can be efficiently prepared from allyl alcohol derivatives using a simple organic material, thiourea, as an organic catalyst.

본 발명에 따르면, 기존의 방법들과 비교하여 보다 경제적인 유기촉매를 사용하여 높은 수율과 짧은 시간에 효율적으로 다이하이드로퀴놀린 유도체를 합성하는 장점을 갖고 있다.According to the present invention, it is advantageous to synthesize dihydroquinoline derivatives efficiently in a short time by using a more economical organic catalyst in comparison with existing methods.

본 발명의 상기 및 그 밖의 목적과 새로운 특징은 본 명세서에 의하여 더욱 명확해 질 것이다.These and other objects and novel features of the present invention will become more apparent from the description below.

먼저 본 발명에 따른 다이하이드로퀴놀린 유도체의 제조방법의 특징에 대해 설명한다. First, the characteristics of the method for producing the dihydroquinoline derivative according to the present invention will be described.

본 발명에서는 알릴 알코올 유도체(allyl alcohol derivatives)로부터 티오유레아 촉매를 이용하여 다이하이드로퀴놀린 유도체를 효율적으로 제조할 수 있다. In the present invention, dihydroquinoline derivatives can be efficiently produced from allyl alcohol derivatives using thiourea catalysts.

본 발명에서는 알릴 알코올 유도체(allyl alcohol derivatives)로부터 톨루엔 용매 하에서 HBr(20 mol %)과 유기촉매 티오유레아 (10 mol %)를 이용하여 다이하이드로퀴놀린 유도체를 합성하는 방법을 제공하는 것이다.
The present invention provides a method for synthesizing dihydroquinoline derivatives from allyl alcohol derivatives using HBr (20 mol%) and organic catalyst thiourea (10 mol%) in a toluene solvent.

본 발명의 일 실시 예에 따른 키랄 다이하이드로퀴놀린 유도체의 제조방법은 톨루엔 용매 하에서 HBr(20 mol %)과 하기 [화학식1]의 유기촉매 티오유레아(10 mol %)를 이용하여 [반응식 1]과 같이 [화학식 2]의 구조를 갖는 알릴 알코올 유도체(allyl alcohol derivatives)를 반응시켜 다이하이드로퀴놀린 유도체(화학식 3)를 제조할 수 있다. A method for preparing a chiral dihydroquinoline derivative according to an embodiment of the present invention comprises reacting HBr (20 mol%) with an organic catalyst thiourea (10 mol%) of the following formula (1) in a toluene solvent Similarly, a dihydroquinoline derivative (Formula 3) can be prepared by reacting allyl alcohol derivatives having the structure of Formula 2.

상기 제조방법은 유기촉매를 이용하여 높은 수율의 다이하이드로퀴놀린 유도체(화학식 3)를 짧은 시간에 효율적으로 제조하기 위한 것이다.
The above production method is for efficiently producing a dihydroquinoline derivative (Formula 3) with high yield in a short time using an organic catalyst.

[화학식 1][Chemical Formula 1]

Figure 112014102093914-pat00004

Figure 112014102093914-pat00004

[화학식 2](2)

Figure 112014102093914-pat00005

Figure 112014102093914-pat00005

상기 [화학식 2]에서 상기 R1은 수소 또는 메틸이다. 상기 R2는 C6-C14의 아릴기이다. 상기 아릴기는 C1-C3의 알콕시기, 알킬기 또는 할로겐으로 치환될 수 있다.
In the above formula (2), R 1 is hydrogen or methyl. R 2 is a C 6 -C 14 aryl group. The aryl group may be substituted with a C 1 -C 3 alkoxy group, an alkyl group or a halogen.

다이하이드로퀴놀린 유도체는 하기 [화학식 3]의 구조를 갖는다.The dihydroquinoline derivative has a structure represented by the following formula (3).

[화학식 3](3)

Figure 112014102093914-pat00006
Figure 112014102093914-pat00006

R1 및 R2는 위에서 정의한 바와 같다. 상기 Ts는 토실기(tosyl)이다.R 1 and R 2 are as defined above. Ts is a tosyl.

[반응식 1] [Reaction Scheme 1]

Figure 112014102093914-pat00007
Figure 112014102093914-pat00007

상기 반응식 1에서 상기 R1은 수소 또는 메틸이다. 상기 R2는 C6-C14의 아릴기이다. 상기 아릴기는 C1-C3의 알콕시기, 알킬기 또는 할로겐으로 치환될 수 있다. 상기 Ts는 토실기(tosyl)이다.Wherein R < 1 > is hydrogen or methyl. R 2 is a C 6 -C 14 aryl group. The aryl group may be substituted with a C 1 -C 3 alkoxy group, an alkyl group or a halogen. Ts is a tosyl.

이하, 하기 실시 예 등에 의하여 본 발명을 더욱 상세하게 설명하고자 한다. 다만, 하기 실시 예 등은 본 발명을 예시하기 위한 것일 뿐 본 발명의 범위가 이들만으로 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are intended to illustrate the present invention, but the scope of the present invention is not limited thereto.

본 발명의 바람직한 일 실시예에 따라, 상기 [반응식 1]과 같이, 톨루엔 용매 하에서 HBr(20 mol %)과 하기 [화학식1]의 구조를 갖는 유기촉매 티오유레아(10 mol %)를 이용하여 [반응식 1]과 같이 [화학식 2]의 구조를 갖는 알릴 알코올 유도체(allyl alcohol derivatives)를 반응시켜 다이하이드로퀴놀린 유도체(화학식 3)를 합성하였으며 그 결과를 표 1에 나타내었다.
According to a preferred embodiment of the present invention, HBr (20 mol%) and organic catalyst thiourea (10 mol%) having a structure represented by the following formula (1) were reacted in a toluene solvent as in the above Reaction Scheme 1 [ The dihydroquinoline derivative (Formula 3) was synthesized by reacting allyl alcohol derivatives having the structure of Formula 2 as shown in Scheme 1, and the results are shown in Table 1.

[표 1]a [Table 1] a

Figure 112014102093914-pat00008
Figure 112014102093914-pat00008

a수율은 정제하여 측정하였다.
 a The yield was determined by purification.

[실시예 1][Example 1]

(4-Methyl-2-phenyl-1-tosyl-1,2-dihydroquinoline (3a): (4-Methyl-2-phenyl-1-tosyl-1,2-dihydroquinoline (3a)

Figure 112014102093914-pat00009
Figure 112014102093914-pat00009

5 mL 둥근 플라스크에 2-aminophenyl-1-en-3-ol 2a (0.3 mmol), [화학식 1] 촉매 (0.03 mmol, 10 mol %), 톨루엔 (1.0 mL), 및 HBr (0.06 mmol)을 넣고 30분 동안 상온에서 교반한다. 반응 진행이 완료되면 반응혼합물을 농축하여 컬럼크로마토그래피(EtOAc/hexane = 1:5)로 분리정제하여 [화학식 3]의 생성물 3a를 얻는다. 2-aminophenyl-1-en-3-ol 2a (0.3 mmol), the catalyst (0.03 mmol, 10 mol%), toluene (1.0 mL) and HBr (0.06 mmol) were placed in a 5 mL round- Stir at room temperature for 30 minutes. When the reaction is completed, the reaction mixture is concentrated and then separated and purified by column chromatography (EtOAc / hexane = 1: 5) to obtain the product 3a of the formula (3).

1H NMR (400 MHz, CDCl3) δ = 7.63 (d, J=7.8Hz,1H),7.417.32 (m, 4H), 7.24-7.18 (m, 4H), 7.14-7.08 (m, 3H), 6.97 (d, J=7.8Hz,1H), 5.91(d,J=4.2Hz,1H), 5.63(d,J=4.2Hz,1H), 2.35(s,3H), 1.72(s,3H);13C NMR (100 MHz, CDCl3) δ= 143.5, 138.5, 136.1, 132.9, 129.1, 128.6, 128.4, 128.2, 127.9, 127.6, 127.4, 127.2, 126.5, 126.3, 125.5, 57.0, 21.7, 21.5.
1 H NMR (400 MHz, CDCl 3) δ = 7.63 (d, J = 7.8Hz, 1H), 7.417.32 (m, 4H), 7.24-7.18 (m, 4H), 7.14-7.08 (m, 3H) , 6.97 (d, J = 7.8Hz , 1H), 5.91 (d, J = 4.2Hz, 1H), 5.63 (d, J = 4.2Hz, 1H), 2.35 (s, 3H), 1.72 (s, 3H) ; 13 C NMR (100 MHz, CDCl 3 )? = 143.5, 138.5, 136.1, 132.9, 129.1, 128.6, 128.4, 128.2, 127.9, 127.6, 127.4, 127.2, 126.5, 126.3, 125.5, 57.0, 21.7, 21.5.

[실시예 2][Example 2]

실시예 1과 동일한 방법으로 진행하여 [화학식 3]를 얻었다.The procedure of Example 1 was followed to obtain the compound of formula (3).

2-Phenyl-1-tosyl-1,2-dihydroquinoline(3b):2-Phenyl-1-tosyl-1,2-dihydroquinoline (3b):

Figure 112014102093914-pat00010
Figure 112014102093914-pat00010

1H NMR (400 MHz, CDCl3) δ= 7.64 (d, J=7.9Hz,1H),7.38-7.30 (m, 4H), 7.26-7.18 (m, 4H), 7.14-7.06 (m, 3H), 6.95 (d, J=7.9Hz,1H), 6.27(d,J=9.6Hz,1H), 6.02(d,J=6.0Hz,1H), 5.87(dd,J=9.6,6.0Hz,1H), 2.34(s,3H);13C NMR (100MHz,CDCl3) δ= 143.4, 138.4, 136.1, 132.9, 129.1, 128.6, 128.4, 128.2, 127.9, 127.6, 127.4, 127.2, 126.5, 126.3, 125.5, 57.0, 21.5.25.84, 23.16.
 1 H NMR (400 MHz, CDCl 3) δ = 7.64 (d, J = 7.9Hz, 1H), 7.38-7.30 (m, 4H), 7.26-7.18 (m, 4H), 7.14-7.06 (m, 3H) , 6.95 (d, J = 7.9Hz , 1H), 6.27 (d, J = 9.6Hz, 1H), 6.02 (d, J = 6.0Hz, 1H), 5.87 (dd, J = 9.6,6.0Hz, 1H) , ≪ / RTI > 2.34 (s, 3H); 13 C NMR (100 MHz, CDCl 3 )? = 143.4, 138.4, 136.1, 132.9, 129.1, 128.6, 128.4, 128.2, 127.9, 127.6, 127.4, 127.2, 126.5, 126.3, 125.5, 57.0, 21.5.25.84, 23.16.

[실시예 3][Example 3]

실시예 1과 동일한 방법으로 진행하여 [화학식 3]를 얻었다.The procedure of Example 1 was followed to obtain the compound of formula (3).

2-(4-Methoxyphenyl)-1-tosyl-1,2-dihydroquinoline(3c):2- (4-Methoxyphenyl) -1-tosyl-1,2-dihydroquinoline (3c):

Figure 112014102093914-pat00011
Figure 112014102093914-pat00011

1H NMR (400 MHz, CDCl3) δ= 7.63 (d,J=7.6Hz,1H), 7.33(d,J=8.0Hz,2H), 7.23-7.18 (m, 3H), 7.14-7.08 (m, 3H), 7.04 (d, J=8.0Hz,2H), 6.95(d,J=7.6Hz,1H), 6.26(d,J=9.6Hz,1H), 5.98(d,J=6.0Hz,1H), 5.87(dd,J=9.6,6.0Hz,1H), 3.81(s,3H); 2.35(s,3H); 13C NMR( 100MHz, CDCl3) δ= 143.3, 137.7, 136.2, 135.3, 132.9, 129.2, 129.1, 128.7, 128.2, 127.7, 127.4, 127.3, 126.7, 126.4, 126.2, 126.2, 125.4, 56.8, 21.6, 21.1.
 1 H NMR (400 MHz, CDCl 3) δ = 7.63 (d, J = 7.6Hz, 1H), 7.33 (d, J = 8.0Hz, 2H), 7.23-7.18 (m, 3H), 7.14-7.08 (m , 3H), 7.04 (d, J = 8.0Hz, 2H), 6.95 (d, J = 7.6Hz, 1H), 6.26 (d, J = 9.6Hz, 1H), 5.98 (d, J = 6.0Hz, 1H ), 5.87 (dd, J = 9.6, 6.0 Hz, 1H), 3.81 (s, 3H); 2.35 (s, 3 H); 13 C NMR (100MHz, CDCl 3 ) δ = 143.3, 137.7, 136.2, 135.3, 132.9, 129.2, 129.1, 128.7, 128.2, 127.7, 127.4, 127.3, 126.7, 126.4, 126.2, 126.2, 125.4, 56.8, 21.6, 21.1 .

[실시예 4][Example 4]

실시예 1과 동일한 방법으로 진행하여 [화학식 3]를 얻었다.The procedure of Example 1 was followed to obtain the compound of formula (3).

2-(4-Chlorophenyl)-1-tosyl-1,2-dihydroquinoline(3d):2- (4-Chlorophenyl) -1-tosyl-1,2-dihydroquinoline (3d):

Figure 112014102093914-pat00012
Figure 112014102093914-pat00012

1H NMR (400 MHz, CDCl3) δ= 7.63 (d, J=8.0 Hz,1H), 7.32(d,J=8.0 Hz,2H), 7.27(d,J=8.0 Hz,2H), 7.24-7.10 (m, 6H), 6.96 (d, J=8.0 Hz,1H), 6.28(d,J=9.6 Hz,1H), 5.98(d,J=6.0,1H), 5.85(dd,J=9.6, 6.0 Hz,1H), 2.35(s,3H); 13C NMR (100MHz, CDCl3) δ= 143.6; 136.9, 136.0133.8, 132.7, 129.2, 128.9, 128.6, 128.5, 127.6, 127.2, 126.6, 126.4, 126.0, 125.9, 56.2, 21.6.
 1 H NMR (400 MHz, CDCl 3) δ = 7.63 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.24- 7.10 (m, 6H), 6.96 (d, J = 8.0 Hz, 1H), 6.28 (d, J = 9.6 Hz, 1H), 5.98 (d, J = 6.0,1H), 5.85 (dd, J = 9.6, 6.0 Hz, 1 H), 2.35 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 )? = 143.6; 136.9, 136.0133.8, 132.7, 129.2, 128.9, 128.6, 128.5, 127.6, 127.2, 126.6, 126.4, 126.0, 125.9, 56.2, 21.6.

[실시예 5][Example 5]

실시예 1과 동일한 방법으로 진행하여 [화학식 3]를 얻었다.The procedure of Example 1 was followed to obtain the compound of formula (3).

1-(Naphthalen-1-yl)-1-tosyl-1,2-dihydroquinoline(3e):1- (Naphthalen-1-yl) -1-tosyl-1,2-dihydroquinoline (3e):

Figure 112014102093914-pat00013
Figure 112014102093914-pat00013

1H NMR (CDCl3,400MHz) δ= 7.76-7.58 (6H, m), 7.40-7.33 (4H, m), 7.07-7.19 (4H, m),6.96 (1H, d, J = 1.62, 7.33 Hz), 6.33 (1H, d, J = 9.60 Hz), 6.16 (1H, d, J = 5.86 Hz), 5.93 (1H, dd, J = 5.88, 9.58 Hz), 2.34 (3H, s); 13C NMR (CDCl3, 100MHz) δ= 143.4, 136.1, 135.6,133.0, 132.8, 128.7, 128.4, 128.3, 128.0, 127.7, 127.5, 126.5, 126.3, 126.1, 126.0, 125.9, 125.7, 57.0, 21.5.
 1 H NMR (CDCl 3, 400MHz ) δ = 7.76-7.58 (6H, m) , 7.40-7.33 (4H, m), 7.07-7.19 (4H, m), 6.96 (1H, d, J = 1.62, 7.33 Hz), 6.33 (1H, d, J = 9.60 Hz), 6.16 (1H, d, J = 5.86 Hz), 5.93 (1H, dd, J = 5.88, 9.58 Hz), 2.34 (3H, s); 13 C NMR (CDCl 3 , 100 MHz)? = 143.4, 136.1, 135.6, 133.0, 132.8, 128.7, 128.4, 128.3, 128.0, 127.7, 127.5, 126.5, 126.3, 126.1, 126.0, 125.9, 125.7, 57.0, 21.5.

[실시예 6][Example 6]

실시예 1과 동일한 방법으로 진행하여 [화학식 3]를 얻었다.The procedure of Example 1 was followed to obtain the compound of formula (3).

((E)-2-Styryl-1-tosyl-1,2-dihydroquinoline(3f):(( E ) -2-Styryl-1-tosyl-1,2-dihydroquinoline (3f):

Figure 112014102093914-pat00014
Figure 112014102093914-pat00014

1HNMR(400MHz,CDCl3) δ= 7.77-7.71 (m, 1H), 7.35-7.31 (m, 2H), 7.28-7.26 (m, 1H), 7.26-7.10 (m, 6H), 7.09-06 (m, 2H), 6.98-6.93 (m, 1H), 6.55-6.50 (m, 1H), 6.19-6.15 (m, 1H), 6.05-6.03 (m, 1H), 5.75-5.69 (m, 1H), 5.59-5.56 (m, 1H), 2.34 (s, 3H); 13C NMR (125MHz, CDCl3) δ= 143.5. 136.4, 136.0, 133.0, 132.1, 129.1, 128.4, 128.2, 127.8, 127.5, 127.2, 126.6, 126.5, 126.0, 125.4, 125.3, 56.2, 21.7.
 1 H NMR (400 MHz, CDCl 3 )? = 7.77-7.71 (m, 1H), 7.35-7.31 (m, 2H), 7.28-7.26 (m, 2H), 6.98-6.93 (m, IH), 6.55-6.50 (m, IH), 6.19-6.15 5.59-5.56 (m, 1 H), 2.34 (s, 3 H); 13 C NMR (125 MHz, CDCl 3 )? = 143.5. 136.4, 136.0, 133.0, 132.1, 129.1, 128.4, 128.2, 127.8, 127.5, 127.2, 126.6, 126.5, 126.0, 125.4, 125.3, 56.2, 21.7.

Claims (1)

하기 [화학식 1]의 1,3-디페닐티오유레아(1,3-diphenylthiourea) 촉매와 산 촉매 HBr를 이용하여, 하기 [화학식 2]의 구조를 갖는 알릴 알코올 유도체(allyl alcohol derivatives)를 하기 [반응식 1]과 같이 반응시키는 것을 특징으로 하는 다이하이드로퀴놀린 유도체의 제조 방법.
[반응식 1]
Figure 112016013376720-pat00015

상기 반응식 1에서 상기 R1은 수소 또는 메틸이다. 상기 R2는 C6-C14의 아릴기이다. 상기 아릴기는 C1-C3의 알콕시기, 알킬기 또는 할로겐으로 치환될 수 있다. 상기 Ts는 토실기(tosyl)이다.
[화학식 1]
Figure 112016013376720-pat00016

[화학식 2]
Figure 112016013376720-pat00017

상기 [화학식 2]에서 상기 R1은 수소 또는 메틸이다. 상기 R2는 C6-C14의 아릴기이다. 상기 아릴기는 C1-C3의 알콕시기, 알킬기 또는 할로겐으로 치환될 수 있다.Allyl alcohol derivatives having a structure represented by the following formula (2) are prepared by using 1,3-diphenylthiourea catalyst of the following formula (1) and acid catalyst HBr [ Wherein R < 1 > and R < 2 >
[Reaction Scheme 1]
Figure 112016013376720-pat00015

Wherein R < 1 > is hydrogen or methyl. R 2 is a C 6 -C 14 aryl group. The aryl group may be substituted with a C 1 -C 3 alkoxy group, an alkyl group or a halogen. Ts is a tosyl.
[Chemical Formula 1]
Figure 112016013376720-pat00016

(2)
Figure 112016013376720-pat00017

In the above formula (2), R 1 is hydrogen or methyl. R 2 is a C 6 -C 14 aryl group. The aryl group may be substituted with a C 1 -C 3 alkoxy group, an alkyl group or a halogen.
KR1020140145237A 2014-10-24 2014-10-24 Synthetic method of dihydroquinoline derivatives KR101613065B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020140145237A KR101613065B1 (en) 2014-10-24 2014-10-24 Synthetic method of dihydroquinoline derivatives

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020140145237A KR101613065B1 (en) 2014-10-24 2014-10-24 Synthetic method of dihydroquinoline derivatives

Publications (1)

Publication Number Publication Date
KR101613065B1 true KR101613065B1 (en) 2016-04-20

Family

ID=55917617

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020140145237A KR101613065B1 (en) 2014-10-24 2014-10-24 Synthetic method of dihydroquinoline derivatives

Country Status (1)

Country Link
KR (1) KR101613065B1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20190033945A (en) * 2017-09-22 2019-04-01 순천향대학교 산학협력단 Synthetic method of tetrahydroisoquinoline derivatives

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
J. Org. Chem. 2012. Vol. 77, pp. 8615-8620

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20190033945A (en) * 2017-09-22 2019-04-01 순천향대학교 산학협력단 Synthetic method of tetrahydroisoquinoline derivatives
KR102051523B1 (en) * 2017-09-22 2019-12-03 순천향대학교 산학협력단 Synthetic method of tetrahydroisoquinoline derivatives

Similar Documents

Publication Publication Date Title
JP3281920B2 (en) Method for producing allylfuran compound
JP6216073B2 (en) Large-scale production method of 1H- [1,2,3] triazole and its intermediate 1-benzyl-1H- [1,2,3] triazole
KR20130142477A (en) Method for preparation of nitrocyclopropane derivatives
KR101613065B1 (en) Synthetic method of dihydroquinoline derivatives
KR20160027536A (en) Process for preparing an intermediate useful for the synthesis of silodosin
KR101416920B1 (en) Method for preparation of δ-nitro ketone derivatives
JP6427787B2 (en) Method for producing dehydrolinalyl acetate (II)
KR101374706B1 (en) Method for preparation of chiral lactone derivatives
KR101856537B1 (en) Synthetic method of tetrahydroisoquinoline derivatives
KR101510245B1 (en) Method for preparation of chiral chlorooxindole derivatives
KR101404614B1 (en) Method for preparation of chiral α-chloro-α-fluoro-β-keto phosphonate derivatives
KR102051523B1 (en) Synthetic method of tetrahydroisoquinoline derivatives
CN116462619B (en) Preparation method of cyclopentenone derivative
KR20130058479A (en) Method for preparation of chiral oxindole derivatives
KR101404613B1 (en) Method for preparation of chiral a-amino ketone derivatives
KR101386604B1 (en) Method for preparation of chiral 1,5-diketone derivatives
KR101461200B1 (en) Method for preparation of chiral lactol derivatives
KR101396304B1 (en) Method for preparation of chiral indole succinic acid derivatives
KR101428906B1 (en) Method for preparation of chiral naphthoquinone derivatives
KR101815001B1 (en) 4-Substituted-5-membered-ring-sulfamidate-5-phosphonate compounds and Method for the stereoselective preparation thereof
JP2013043831A (en) TERTIARY α-TRIFLUOROMETHYL KETONE DERIVATIVE, AND METHOD FOR PRODUCING THE SAME
KR101523191B1 (en) Method for preparation of 3-hydroxy-3-(2-oxoalkyl)-2-oxindole derivatives
JP4064645B2 (en) New production method of polysubstituted cycloalkenes
KR101506297B1 (en) Method for the stereoselective preparation of 2-substituted morpholine derivatives
JP2024126018A (en) Ruthenium complex, its method of production and method of production of allylamine compound using the same

Legal Events

Date Code Title Description
E701 Decision to grant or registration of patent right
GRNT Written decision to grant
FPAY Annual fee payment

Payment date: 20190412

Year of fee payment: 4