KR101590592B1 - Manufacturing method of dipyrryl ketones and dipyrryl ketones made by the same - Google Patents

Manufacturing method of dipyrryl ketones and dipyrryl ketones made by the same Download PDF

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KR101590592B1
KR101590592B1 KR1020140003062A KR20140003062A KR101590592B1 KR 101590592 B1 KR101590592 B1 KR 101590592B1 KR 1020140003062 A KR1020140003062 A KR 1020140003062A KR 20140003062 A KR20140003062 A KR 20140003062A KR 101590592 B1 KR101590592 B1 KR 101590592B1
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김재녕
김세희
임진우
유진
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전남대학교산학협력단
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Abstract

본 발명은 디피롤 케톤의 제조 방법 및 이에 의하여 제조된 디피롤 케톤에 관한 것이다.
본 발명에 의한 디피롤 케톤의 제조 방법은 2-카르복시산 피롤 화합물로부터 간단한 공정에 의해 높은 수율로 디피롤 케톤을 제조할 수 있다.The present invention relates to a process for the preparation of dipropyl ketone and to the dipropyl ketone thereby prepared.
The process for preparing dipyrrole ketone according to the present invention can produce dipyrrole ketone in a high yield from a 2-carboxylate pyrrole compound by a simple process.

Description

디피롤 케톤의 제조 방법 및 이에 의하여 제조된 디피롤 케톤{MANUFACTURING METHOD OF DIPYRRYL KETONES AND DIPYRRYL KETONES MADE BY THE SAME}TECHNICAL FIELD [0001] The present invention relates to a method for producing dipyrrole ketone and a dipyrrole ketone prepared by the method,

본 발명은 디피롤 케톤의 제조 방법 및 이에 의하여 제조된 디피롤 케톤에 관한 것이다.
The present invention relates to a process for the preparation of dipropyl ketone and to the dipropyl ketone thereby prepared.

디피롤 케톤 유사체들은 포르피린 유도체, 옥소프롤린 유도체 및 10-oxo-bilirubin 등의 제조의 전구체로 사용되기 때문에 합성 방법에 대해 연구가 꾸준히 되고 있다. Dipyrrole ketone analogs are used as precursors for the preparation of porphyrin derivatives, oxoproline derivatives and 10-oxo-bilirubin, and therefore research on the synthesis methods has been steadily progressing.

종래 디피롤 케톤은 디피롤메탄의 세륨암모늄나이트레이트(cerium ammonium nitrate)와의 산화 반응에 의하여 제조되거나, 피롤 카르복시산으로부터 유도된 무수물과 피롤의 아실화 반응에 의해 제조되는 방법이 보고되었다. 그러나 여전히 보다 간이한 방법으로 고수율의 디피롤 케톤을 제조하는 방법에 대한 요구가 있는 실정이다.
Conventional dipyrrole ketones have been reported to be prepared by an oxidation reaction of diphrylyl methane with cerium ammonium nitrate or by an acylation reaction of pyrrole with anhydrides derived from pyrrole carboxylic acid. However, there is still a need for a process for producing high yield dipropyl ketones in a simpler manner.

Can. J. Chem. 1976, 54, 411-414Can. J. Chem. 1976, 54, 411-414 J. Org. Chem. 2005, 70(25), 10607-10610J. Org. Chem. 2005, 70 (25), 10607-10610

본 발명은 종래에 사용되지 않은 새로운 방법으로 디피롤 케톤을 제조할 수 있는 디피롤 케톤의 제조 방법 및 이에 의하여 제조된 디피롤 케톤을 제공하는 것을 목적으로 한다.
It is an object of the present invention to provide a process for producing dipyrrole ketone capable of producing dipyrrole ketone by a novel method which has not been conventionally used, and to provide a dipyrrole ketone produced thereby.

본 발명은 상기와 같은 과제를 해결하기 위하여 The present invention has been made to solve the above problems

아래 화학식 1 로 표시되는 2-카르복시산 피롤 화합물을 준비하는 제 1 단계;A first step of preparing a 2-carboxylic acid pyrrole compound represented by the following formula (1);

[화학식 1][Chemical Formula 1]

Figure 112014002478358-pat00001
Figure 112014002478358-pat00001

(상기 화학식 1 에서, R1 내지 R4 는 서로 독립적으로 수소, 탄소수 1 내지 10의 알킬기, 탄소수 1 내지 10의 알케닐기, 탄소수 5 내지 10의 아릴기, 탄소수 1 내지 5의 알콕시기로 치환된 탄소수 6 내지 15의 아릴기, 탄소수 3 내지 10의 헤테로 아릴기, 벤질기, 중 어느 하나임)
(In the above formula 1, R < 1 > To R 4 is independently selected from the group consisting of hydrogen, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 1 to 10 carbon atoms, an aryl group having 5 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms substituted with an alkoxy group having 1 to 5 carbon atoms, A heteroaryl group having 1 to 10 carbon atoms, or a benzyl group)

상기 화학식 1로 표시되는 2-카르복시산 피롤 화합물을 유기 용매에 용해시키고 아래 화학식 2로 표시되는 화합물과 15 ℃ 내지 35 ℃에서 2 시간 내지 24 시간 반응시키는 제 2 단계; 를 포함하는 디피롤 케톤의 제조 방법을 제공한다.A second step of dissolving the 2-carboxylate pyrrole compound represented by the formula (1) in an organic solvent and reacting with a compound represented by the following formula (2) at 15 ° C to 35 ° C for 2 to 24 hours; ≪ RTI ID = 0.0 > a < / RTI > dipropyl ketone.

[화학식 2](2)

Figure 112014002478358-pat00002
Figure 112014002478358-pat00002

(상기 화학식 2에서, X 는 F, Cl, Br 중 어느 하나임)
(In the above formula (2), X is any one of F, Cl and Br)

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 화학식 1이 1-Benzyl-3,5-diphenyl-1H-pyrrole-2-carboxylic acid이고 상기 화학식 2를 TFAA(trifluoroacetic anhydride)라고 하면 아래와 같은 메카니즘에 의하여 4a 로 표시되는 화합물과 I 로 표시되는 중간 화합물이 생성되고, 생성된 I 로 표시되는 중간 화합물이 다시 4a 로 표시되는 화합물과 반응하여 디피롤 케톤이 생성된다. In the method of Diffie roll ketone according to the invention, the formula (1) is 1-Benzyl-3,5-diphenyl- 1 H -pyrrole-2-carboxylic acid and speaking the formula 2 TFAA (trifluoroacetic anhydride) as shown below By the mechanism, a compound represented by 4a and an intermediate compound represented by I are produced, and an intermediate compound represented by I is reacted with a compound represented by 4a to generate dipyrrole ketone.

Figure 112014002478358-pat00003

Figure 112014002478358-pat00003

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 제 2 단계는 아래 화학식 3으로 표시되는 피롤 화합물을 더 포함하여 반응시키는 것을 특징으로 한다.In the process for preparing dipyrrole ketone according to the present invention, the second step is characterized by further comprising a pyrrole compound represented by the following general formula (3).

[화학식 3](3)

Figure 112014002478358-pat00004
Figure 112014002478358-pat00004

(상기 화학식 3에서 R5 내지 R8 은 서로 독립적으로 수소, 탄소수 1 내지 10의 알킬기, 탄소수 1 내지 10의 알케닐기, 탄소수 5 내지 10의 아릴기, 탄소수 1 내지 5의 알콕시기로 치환된 탄소수 6 내지 15의 아릴기, 탄소수 3 내지 10의 헤테로 아릴기, 벤질기, 중 어느 하나임)(Wherein R < 5 > To R 8 is independently selected from the group consisting of hydrogen, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 1 to 10 carbon atoms, an aryl group having 5 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms substituted with an alkoxy group having 1 to 5 carbon atoms, A heteroaryl group having 1 to 10 carbon atoms, or a benzyl group)

상기 화학식 3으로 표시되는 피롤 화합물은 본 발명자에 의하여 발표된 논문(Kim, S. H.; Lim, J. W.; Lim, C. H.; Kim, J. N. Bull. Korean Chem. Soc. 2012, 33, 620-624.)을 참조하여 제조할 수 있으며, 상기 제 2 단계에서 피롤 화합물을 더 포함하는 경우, 비대칭 디피롤 케톤을 제조할 수 있는 이점이 있다.
The pyrrole compound represented by the above-described formula (3) can be prepared by the method described in the present invention (Kim, SH; Lim, JW; Lim, CH; Kim, JN Bull. Korean Chem. Soc. 2012, 33, 620-624) In the case where the pyrrole compound is further contained in the second step, there is an advantage that an asymmetric dipyrrole ketone can be prepared.

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 유기 용매는 2-카르복시산 피롤 화합물을 용해 시킬 수 있는 용매라면 어느 것을 사용하여도 좋다. 구체적으로 dichloromethane(CH2Cl2), tetrahydrofuran(THF), N,N-dimethylformamide(DMF), acetonitrile(CH3CN), 및 이들의 혼합물에서 선택될 수 있다.In the process for producing dipyrrole ketone according to the present invention, any solvent may be used as long as it is a solvent capable of dissolving a pyrrole 2-carboxylate compound. Specifically, it can be selected from dichloromethane (CH 2 Cl 2 ), tetrahydrofuran (THF), N, N-dimethylformamide (DMF), acetonitrile (CH 3 CN), and mixtures thereof.

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 화학식 2로 표시되는 화합물은 0.5 내지 2.0 당량비로 혼합될 수 있으며, 바람직하게는 0.5 내지 1.0 당량비로 혼합될 수 있다.In the process for preparing dipyrrole ketones according to the present invention, the compound represented by Formula 2 may be mixed in an amount of 0.5 to 2.0 equivalents, preferably 0.5 to 1.0 equivalents.

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 제 2 단계에서 15 ℃ 내지 35 ℃에서 2 시간 내지 24 시간 반응시키기 이전에 0 내지 5 ℃에서 1 내지 10 분 동안 반응시키는 단계를 더 포함하는 것을 특징으로 한다. 저온에서 수 분 동안 반응 시키는 경우 이후 상온에서의 반응 시간을 감소시키는 효과가 있다. In the method for producing dipyrrole ketone according to the present invention, the method further comprises a step of reacting at 0 to 5 ° C for 1 to 10 minutes before reacting at 15 ° C to 35 ° C for 2 to 24 hours in the second step . When the reaction is carried out at low temperature for several minutes, the reaction time at room temperature is reduced.

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 화학식 1 또는 화학식 2는 아래 화학식 4 내지 11 에서 선택된 것을 특징으로 한다.In the process for preparing dipyrrole ketone according to the present invention, the above-mentioned formula (1) or (2) is selected from the following formulas (4) to (11).

Figure 112014002478358-pat00005
Figure 112014002478358-pat00005

Figure 112014002478358-pat00006
Figure 112014002478358-pat00006

Figure 112014002478358-pat00007
Figure 112014002478358-pat00007

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 화학식 2로 표시되는 화합물은 TFAA(trifluoroacetic anhydride) 인 것을 특징으로 한다.In the process for preparing dipyrrole ketone according to the present invention, the compound represented by Formula 2 is TFAA (trifluoroacetic anhydride).

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 화학식 1로 표시되는 2-카르복시산 피롤 화합물을 준비하는 단계는In the process for preparing dipyrrole ketone according to the present invention, the step of preparing the 2-carboxylate pyrrole compound represented by the above formula (1)

tetrahydrofuran(THF), methanol, 및 H2O 가 2:2:1 의 부피비로 혼합된 용매를 준비하는 단계;preparing a solvent in which tetrahydrofuran (THF), methanol, and H 2 O are mixed in a volume ratio of 2: 2: 1;

상기 용매에 아래 화학식 12로 표시되는 화합물 및 NaOH 또는 KOH 를 혼합하는 단계; 및Mixing the compound represented by the following formula (12) and NaOH or KOH in the solvent; And

상기 혼합 용액을 40 내지 60 ℃ 의 온도에서 36 시간 내지 42 시간 동안 반응시키는 단계; 를 포함하는 것을 특징으로 한다.Reacting the mixed solution at a temperature of 40 to 60 DEG C for 36 to 42 hours; And a control unit.

[화학식 12][Chemical Formula 12]

Figure 112014002478358-pat00008
Figure 112014002478358-pat00008

(상기 화학식 12 에서, R1 내지 R4 는 서로 독립적으로 수소, 탄소수 1 내지 10의 알킬기, 탄소수 1 내지 10의 알케닐기, 탄소수 5 내지 10의 아릴기, 탄소수 1 내지 5의 알콕시기로 치환된 탄소수 6 내지 15의 아릴기, 탄소수 3 내지 10의 헤테로 아릴기, 벤질기, 중 어느 하나이고, 중 어느 하나이고,Wherein R 1 to R 4 independently represent hydrogen, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 1 to 10 carbon atoms, an aryl group having 5 to 10 carbon atoms, an alkoxy group substituted with an alkoxy group having 1 to 5 carbon atoms An aryl group having 6 to 15 carbon atoms, a heteroaryl group having 3 to 10 carbon atoms, and a benzyl group,

R9 는 탄소수 1 내지 10의 알킬기 임)And R < 9 > is an alkyl group having 1 to 10 carbon atoms)

본 발명에 의한 디피롤 케톤의 제조 방법에 있어서, 상기 NaOH 또는 KOH 는 5 내지 10 당량 포함되는 것을 특징으로 한다.
In the method for producing dipyrrole ketone according to the present invention, NaOH or KOH is contained in an amount of 5 to 10 equivalents.

본 발명은 또한, 본 발명의 제조 방법에 의하여 제조된 디피롤 케톤을 제공한다. The present invention also provides dipropyl ketones prepared by the process of the present invention.

본 발명에 의하여 제조된 디피롤 케톤은 아래 화학식 13 내지 27로 표시되는 화합물 중 어느 하나인 것을 특징으로 한다.The dipyrrole ketone prepared by the present invention is characterized by being any one of the compounds represented by the following formulas (13) to (27).

Figure 112014002478358-pat00009
Figure 112014002478358-pat00009

Figure 112014002478358-pat00010
Figure 112014002478358-pat00010

Figure 112014002478358-pat00011
Figure 112014002478358-pat00011

Figure 112014002478358-pat00012
Figure 112014002478358-pat00012

Figure 112014002478358-pat00013
Figure 112014002478358-pat00013

(상기 화학식 13 내지 17 에서, n 은 0 내지 3 의 정수임)
(In the above formulas 13 to 17, n is an integer of 0 to 3)

본 발명에 의한 디피롤 케톤의 제조 방법은 2-카르복시산 피롤 화합물로부터 간단한 공정에 의해 높은 수율로 디피롤 케톤을 제조할 수 있다.
The process for preparing dipyrrole ketone according to the present invention can produce dipyrrole ketone in a high yield from a 2-carboxylate pyrrole compound by a simple process.

이하에서는 본 발명을 실시예에 의하여 더욱 상세히 설명한다. 그러나, 본 발명이 이하의 실시예에 의하여 더욱 한정되는 것은 아니다.
Hereinafter, the present invention will be described in more detail by way of examples. However, the present invention is not limited by the following examples.

<< 실시예Example 1> 1>

출발 물질로서 pyrrole-2-carboxylate(1-1)를 준비하고, THF : MeOH : H2O 가 2:2:1 의 비율로 혼합된 용매에서 10 당량의 KOH 와 혼합한 후 50 ℃ 에서 36 시간 동안 반응시켜서 가수분해 화합물 1-2 를 제조하였다. Pyrrole-2-carboxylate (1-1) as a starting material was prepared and mixed with 10 equivalents of KOH in a mixed solvent of THF: MeOH: H 2 O at a ratio of 2: 2: 1, Lt; RTI ID = 0.0 &gt; 1-2. &Lt; / RTI &gt;

Figure 112014002478358-pat00014
Figure 112014002478358-pat00014

상기 가수분해된 화합물 1-2(177 mg) 을 CH2Cl2에 용해시킨 후 TFAA(trifluoroacetic anhydride)를 0.6 당량 첨가하고 20 시간 동안 교반하였다. After the hydrolyzed compound 1-2 (177 mg) was dissolved in CH 2 Cl 2 , 0.6 equivalent of TFAA (trifluoroacetic anhydride) was added and stirred for 20 hours.

생성된 반응물을 증류수로 생성물을 추출하고, hexanes/CH2Cl2/ether가 25:1:1 의 부피비로 혼합된 용매로 컬럼 크로마토그래피를 수행하여 생성물을 정제하였다. 디피롤 케톤 화합물 1-3 은 노란색 고체로 118 mg (수율 73%), 화합물 1-4 는 흰색 고체로 37 mg (수율 24%)으로 정제되었다. The resulting reaction product was extracted with distilled water, and the product was purified by column chromatography using a mixed solvent of hexanes / CH 2 Cl 2 / ether in a volume ratio of 25: 1: 1. Dipyrrole ketone compound 1-3 was purified to 118 mg (yield 73%) as a yellow solid and 37 mg (yield 24%) as a white solid.

Figure 112014002478358-pat00015
Figure 112014002478358-pat00015

Compound 1-3 : yellow solid, mp 74-76 ℃; Compound 1-3: yellow solid, mp 74-76 [deg.] C;

IR(KBr) 1596, 1455, 1180 cm-1; IR (KBr) 1596, 1455, 1180 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 5.10 (d, J = 15.6 Hz, 2H), 5.34 (d, J = 15.6 Hz, 2H), 5.94(s, 2H), 6.74-6.78 (m, 4H), 6.92-7.25 (m, 26H); 1 H NMR (300 MHz, CDCl 3) δ 5.10 (d, J = 15.6 Hz, 2H), 5.34 (d, J = 15.6 Hz, 2H), 5.94 (s, 2H), 6.74-6.78 (m, 4H) , 6.92-7.25 (m, 26H);

13C NMR(75 MHz, CDCl3) δ 49.23, 111.72, 125.93, 126.88 (2C), 127.43, 127.99, 128.11, 128.22, 128.85, 129.61, 130.26, 133.28, 133.69, 135.49, 138.73, 139.90, 178.12; 13 C NMR (75 MHz, CDCl 3 ) 隆 49.23, 111.72, 125.93, 126.88 (2C), 127.43, 127.99, 128.11, 128.22, 128.85, 129.61, 130.26, 133.28, 133.69, 135.49, 138.73, 139.90, 178.12;

ESIMS m/z 645 [M+H]+. ESIMS m / z 645 [M + H] &lt; + &gt;.

Anal. Calcd for C47H36N2O: C, 87.55; H, 5.63; N, 4.34. Anal. Calcd for C 47 H 36 N 2 O: C, 87.55; H, 5.63; N, 4.34.

Found: C, 87.81; H, 5.77; N, 4.19.
Found: C, 87.81; H, 5.77; N, 4.19.

<< 비교예Comparative Example >>

상기 가수분해된 화합물 1-2(177 mg) 을 CH2Cl2 에 용해시킨 후 TFAA(trifluoroacetic anhydride)을 2 당량의 비율로 첨가하고 24시간 동안 상온에서 교반하는 경우 디피롤 케톤 화합물 1-3 은 수율 68%, 부산물인 화합물 1-4 는 11%, 1-5 는 14%로 생성된 반면, TFAA(trifluoroacetic anhydride)을 3 당량의 비율로 첨가한 경우 디피롤 케톤 화합물 1-3 은 수율 31%, 부산물인 화합물 1-4 는 12%, 1-5 는 51%로 생성되었다. When the hydrolyzed compound 1-2 (177 mg) was dissolved in CH 2 Cl 2 and TFAA (trifluoroacetic anhydride) was added in a ratio of 2 equivalents, and the mixture was stirred at room temperature for 24 hours, the dipyrrole ketone compound 1-3 The yield of the Dipyrrole ketone compound 1-3 was 31% when TFAA (trifluoroacetic anhydride) was added in the ratio of 3 equivalents, while the yield of the compound 1-4 was 11% and that of 1-5 was 14% , The byproducts 1-4 were 12%, and 1-5 were 51%.

Figure 112014002478358-pat00016

Figure 112014002478358-pat00016

<< 실시예Example 2> 2>

가수분해 화합물 2-2 를 제조한 후, 아래 반응식에서와 같이 상기 실시예 1과 동일하게 하여 디피롤 케톤 화합물 2-3 을 72% 의 수율로 제조하였다.After the hydrolysis compound 2-2 was prepared, the dipyrrole ketone compound 2-3 was obtained in a yield of 72% in the same manner as in Example 1, as shown in the following reaction formula.

Figure 112014002478358-pat00017
Figure 112014002478358-pat00017

Compound 2-3 : yellow solid, mp 66-68 ℃; Compound 2-3: yellow solid, mp 66-68 [deg.] C;

IR(KBr) 1595, 1456, 1348 cm-1; IR (KBr) 1595, 1456, 1348 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 2.87-2.97 (m, 2H), 3.27-3.37 (m, 2H), 4.24-4.35 (m, 4H), 5.78 (s, 2H), 6.90-6.94 (m, 4H), 7.02-7.22 (m, 20H), 7.30-7.39 (m, 6H); 1 H NMR (300 MHz, CDCl 3) δ 2.87-2.97 (m, 2H), 3.27-3.37 (m, 2H), 4.24-4.35 (m, 4H), 5.78 (s, 2H), 6.90-6.94 (m , 4H), 7.02-7.22 (m, 20H), 7.30-7.39 (m, 6H);

13C NMR (75 MHz, CDCl3) δ 38.57, 47.80, 110.69, 125.77, 126.43, 127.19, 128.17, 128.36, 128.48, 128.81, 128.89, 129.61, 129.98, 132.52, 133.20, 135.58, 138.69, 139.01, 179.58; 13 C NMR (75 MHz, CDCl 3) δ 38.57, 47.80, 110.69, 125.77, 126.43, 127.19, 128.17, 128.36, 128.48, 128.81, 128.89, 129.61, 129.98, 132.52, 133.20, 135.58, 138.69, 139.01, 179.58;

ESIMS m/z 673 [M+H]+. ESIMS m / z 673 [M + H] &lt; + &gt;.

Anal. Calcd for C49H40N2O: C, 87.47; H, 5.99; N, 4.16. Anal. Calcd for C 49 H 4 O N 2 O: C, 87.47; H, 5.99; N, 4.16.

Found: C,87.32; H, 6.10; N, 4.03.
Found: C, 87.32; H, 6.10; N, 4.03.

<< 실시예Example 3> 3>

가수분해 화합물 3-2 를 제조한 후, 아래 반응식에서와 같이 상기 실시예 1과 동일하게 하여 디피롤 케톤 화합물 3-3 을 86% 의 수율로 제조하였다. After the hydrolysis compound 3-2 was prepared, the dipyrrole ketone compound 3-3 was prepared in a yield of 86% in the same manner as in Example 1, as shown in the following reaction formula.

Figure 112014002478358-pat00018
Figure 112014002478358-pat00018

(1) Compound 3-3 : yellow solid, mp 50-52 ℃; (1) Compound 3-3: yellow solid, mp 50-52 DEG C;

IR(KBr) 1594, 1455, 1349 cm-1; IR (KBr) 1594, 1455, 1349 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3)δ 1.86-2.01 (m, 2H), 2.09-2.24 (m, 2H), 2.83-2.54 (m, 4H), 4.10-4.16 (m, 4H), 5.78 (s, 2H), 6.91-7.17 (m, 24H), 7.25-7.30 (m, 6H); 1 H NMR (300 MHz, CDCl 3) δ 1.86-2.01 (m, 2H), 2.09-2.24 (m, 2H), 2.83-2.54 (m, 4H), 4.10-4.16 (m, 4H), 5.78 (s , 2H), 6.91-7.17 (m, 24H), 7.25-7.30 (m, 6H);

13C NMR (75 MHz, CDCl3) δ 32.92, 32.95,45,59, 110.96, 125.76, 127.19, 127.96, 128.16, 128.29, 128.36, 128.78, 129.39, 129.97, 132.50, 133.34, 135.60, 139.10, 141.09, 179.19 (one carbon was overlapped); 13 C NMR (75 MHz, CDCl 3) δ 32.92, 32.95,45,59, 110.96, 125.76, 127.19, 127.96, 128.16, 128.29, 128.36, 128.78, 129.39, 129.97, 132.50, 133.34, 135.60, 139.10, 141.09, 179.19 (one carbon was overlapped);

ESIMS m/z 701 [M+H]+. ESIMS m / z 701 [M + H] &lt; + &gt;.

Anal. Calcd for C51H44N2O: C,87.39; H, 6.33; N, 4.00. Anal. Calcd for C 51 H 44 N 2 O: C, 87.39; H, 6.33; N, 4.00.

Found: C, 87.51; H, 6.56; N, 3.87.
Found: C, 87.51; H, 6.56; N, 3.87.

(2) Compound 3-4 : colorless oil; (2) Compound 3-4: colorless oil;

IR (film) 1603, 1453, 1196 cm-1; IR (film) 1603, 1453, 1196 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 1.82-1.98 (m,2H), 2.44 (t, J = 7.5 Hz, 2H), 3.88 (t, J = 7.5 Hz, 2H), 6.42(d, J = 2.1 Hz, 1H), 6.96-7.34 (m, 14H), 7.44-7.48 (m, 2H); 1 H NMR (300 MHz, CDCl 3) δ 1.82-1.98 (m, 2H), 2.44 (t, J = 7.5 Hz, 2H), 3.88 (t, J = 7.5 Hz, 2H), 6.42 (d, J = 2.1 Hz, 1 H), 6.96-7.34 (m, 14H), 7.44-7.48 (m, 2H);

13C NMR (75 MHz, CDCl3) δ 32.66, 32.70, 46.73, 106.85, 118.73, 124.27, 124.87, 125.37, 126.00, 127.07, 128.27, 128.40, 128.45, 128.60, 128.81, 133.26, 135.35, 135.62, 140.86; 13 C NMR (75 MHz, CDCl 3 ) 隆 32.66, 32.70, 46.73, 106.85, 118.73, 124.27, 124.87, 125.37, 126.00, 127.07, 128.27, 128.40, 128.45, 128.60, 128.81, 133.26, 135.35, 135.62, 140.86;

ESIMS m/z 338 [M+H]+. ESIMS m / z 338 [M + H] &lt; + &gt;.

Anal. Calcd for C25H23N: C, 88.98; H, 6.87; N, 4.15. Anal. Calcd for C 25 H 23 N: C, 88.98; H, 6.87; N, 4.15.

Found: C, 88.85; H, 6.81; N, 4.06.
Found: C, 88.85; H, 6.81; N, 4.06.

<< 실시예Example 4> 4>

가수분해 화합물 4-2 를 제조한 후, 아래 반응식에서와 같이 상기 실시예 1과 동일하게 하여 디피롤 케톤 화합물 4-3 을 76% 의 수율로 제조하였다. After the hydrolysis compound 4-2 was prepared, the dipyrrole ketone compound 4-3 was prepared in a yield of 76% in the same manner as in Example 1, as shown in the following reaction formula.

Figure 112014002478358-pat00019
Figure 112014002478358-pat00019

Compound 4-3 : yellow solid, mp 62-64 ℃;Compound 4-3: yellow solid, mp 62-64 [deg.] C;

IR(KBr) 1590, 1509, 1467, 1345 cm-1; IR (KBr) 1590, 1509, 1467, 1345 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 1.91 (s, 6H), 5.11 (d, J = 15.9 Hz, 2H), 5.44 (d, J = 15.9 Hz, 2H), 5.58 (s, 2H), 6.74-6.80 (m, 4H), 6.97-7.17 (m,16H); 1 H NMR (300 MHz, CDCl 3) δ 1.91 (s, 6H), 5.11 (d, J = 15.9 Hz, 2H), 5.44 (d, J = 15.9 Hz, 2H), 5.58 (s, 2H), 6.74 -6.80 (m, 4H), 6.97-7.17 (m, 16H);

13C NMR (75 MHz, CDCl3) δ 12.27, 48.31, 109.97, 125.46, 126.72, 126.97, 127.05, 128.42, 128.76, 129.48, 133.16, 134.95, 135.80, 138.16, 177.82; 13 C NMR (75 MHz, CDCl 3)? 12.27, 48.31, 109.97, 125.46, 126.72, 126.97, 127.05, 128.42, 128.76, 129.48, 133.16, 134.95, 135.80, 138.16, 177.82;

ESIMS m/z 521 [M+H]+. ESIMS m / z 521 [M + H] &lt; + &gt;.

Anal. Calcd for C37H32N2O: C, 85.35; H, 6.19; N, 5.38. Anal. Calcd for C 37 H 32 N 2 O: C, 85.35; H, 6.19; N, 5.38.

Found: C, 85.47; H, 6.17; N, 5.21.
Found: C, 85.47; H, 6.17; N, 5.21.

<< 실시예Example 5> 5>

가수분해 화합물 5-2 를 제조한 후, 아래 반응식에서와 같이 상기 실시예 1과 동일하게 하여 디피롤 케톤 화합물 5-3 을 63% 의 수율로 제조하였다. After the hydrolysis compound 5-2 was prepared, the dipyrrole ketone compound 5-3 was obtained in a yield of 63% in the same manner as in Example 1, as shown in the following reaction formula.

Figure 112014002478358-pat00020
Figure 112014002478358-pat00020

Compound 5-3 : yellow solid, mp 100-102 ℃; Compound 5-3: yellow solid, mp 100-102 DEG C;

IR(KBr) 1601, 1495, 1453, 1265 cm-1; IR (KBr) 1601, 1495, 1453, 1265 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 6.12 (s, 2H), 6.87-6.92 (m, 4H), 7.15-7.38 (m, 26H); 1 H NMR (300 MHz, CDCl 3 )? 6.12 (s, 2H), 6.87-6.92 (m, 4H), 7.15-7.38 (m, 26H);

13C NMR (75 MHz, CDCl3) δ 111.48, 126.33, 127.09, 127.43, 127.56, 127.84, 128.03, 128.75, 129.13, 129.36, 132.04, 132.07, 133.32, 135.07, 138.77, 139.04, 177.26; 13 C NMR (75 MHz, CDCl 3) δ 111.48, 126.33, 127.09, 127.43, 127.56, 127.84, 128.03, 128.75, 129.13, 129.36, 132.04, 132.07, 133.32, 135.07, 138.77, 139.04, 177.26;

ESIMS m/z 617 [M+H]+. ESIMS m / z 617 [M + H] &lt; + &gt;.

Anal. Calcd for C45H32N2O: C, 87.63; H, 5.23; N, 4.54. Found: C, 87.74; H, 5.56; N, 4.59.
Anal. Calcd for C 45 H 32 N 2 O: C, 87.63; H, 5.23; N, 4.54. Found: C, 87.74; H, 5.56; N, 4.59.

<< 실시예Example 6> 6>

가수분해 화합물 6-2 를 제조한 후, 아래 반응식에서와 같이 상기 실시예 1과 동일하게 하여 디피롤 케톤 화합물 6-3을 75% 의 수율로 제조하였다. After the hydrolysis compound 6-2 was prepared, the dipyrrole ketone compound 6-3 was prepared in a yield of 75% in the same manner as in Example 1, as shown in the following reaction formula.

Figure 112014002478358-pat00021
Figure 112014002478358-pat00021

Compound 6-3 : yellow solid, mp 128-130 ℃; Compound 6-3: yellow solid, mp 128-130 [deg.] C;

(KBr) 1602, 1511, 1455, 1249 cm-1; (KBr) 1602, 1511, 1455, 1249 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 3.72 (s, 6H), 5.97 (s, 2H), 6.69 (d, J = 8.4 Hz, 4H), 6.82-6.87 (m, 4H), 7.02-7.24 (m, 20H); 1 H NMR (300 MHz, CDCl 3) δ 3.72 (s, 6H), 5.97 (s, 2H), 6.69 (d, J = 8.4 Hz, 4H), 6.82-6.87 (m, 4H), 7.02-7.24 ( m, 20H);

13C NMR (75 MHz, CDCl3) δ 55.31, 111.11, 113.14, 126.17, 127.01, 127.35, 127.89, 128.70, 129.29, 130.22, 131.65, 132.18, 132.43, 133.07, 135.25, 139.24, 158.61, 177.39; 13 C NMR (75 MHz, CDCl 3 )? 55.31, 111.11, 113.14, 126.17, 127.01, 127.35, 127.89, 128.70, 129.29, 130.22, 131.65, 132.18, 132.43, 133.07, 135.25, 139.24, 158.61, 177.39;

ESIMS m/z 677 [M+H]+. ESIMS m / z 677 [M + H] &lt; + &gt;.

Anal. Calcd for C47H36N2O3: C, 83.41; H, 5.36; N, 4.14. Anal. Calcd for C 47 H 36 N 2 O 3 : C, 83.41; H, 5.36; N, 4.14.

Found: C, 83.79; H, 5.61; N, 4.02.
Found: C, 83.79; H, 5.61; N, 4.02.

<< 실시예Example 7> 7>

가수분해 화합물 7-2 를 제조한 후, 0.9 당량비의 TFAA를 혼합하고 0 ℃에서 5 분 반응시킨 뒤 상온에서 2 시간 반응 시킨 것을 제외하고는 상기 실시예 1과 동일하게 하여 아래 반응식에서와 같이 디피롤 케톤 화합물 7-3 을 74% 의 수율로 제조하였다. Hydrolysis compound 7-2 was prepared, and TFAA in an equivalent ratio of 0.9 was mixed and reacted at 0 캜 for 5 minutes and then reacted at room temperature for 2 hours. In the same manner as in Example 1, The roll ketone compound 7-3 was prepared in a yield of 74%.

Figure 112014002478358-pat00022
Figure 112014002478358-pat00022

(1) Compound 7-3 : atropisomeric mixture, 3:2; yellow solid, mp 104-106 ℃; (1) Compound 7-3: atropisomeric mixture, 3: 2; yellow solid, mp 104-106 [deg.] C;

IR (KBr) 1603, 1513, 1455, 1210 cm-1; IR (KBr) 1603, 1513, 1455, 1210 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 3.26 (s, 3H*0.6), 3.45(s, 3H*0.4), 3.46 (s, 3H*0.6), 3.47 (s, 3H*0.4), 3.72 (s, 3H*0.6), 3.76 (s, 6H*0.4), 3.79 (s, 3H*0.6), 6.03-7.47 (m, 28H); 1 H NMR (300 MHz, CDCl 3) δ 3.26 (s, 3H * 0.6), 3.45 (s, 3H * 0.4), 3.46 (s, 3H * 0.6), 3.47 (s, 3H * 0.4), 3.72 (s , 3H * 0.6), 3.76 (s, 6H * 0.4), 3.79 (s, 3H * 0.6), 6.03-7.47 (m, 28H);

ESIMS m/z 737 [M+H]+. ESIMS m / z 737 [M + H] &lt; + &gt;.

Anal. Calcd for C49H4N2O5: C,79.87; H, 5.47; N, 3.80. Anal. Calcd for C 49 H 4 N 2 O 5 : C, 79.87; H, 5.47; N, 3.80.

Found: C, 80.03; H, 5.41; N, 3.94.
Found: C, 80.03; H, 5.41; N, 3.94.

(2) Compound 7-4 : white solid, mp 48-50 ℃; (2) Compound 7-4: white solid, mp 48-50 DEG C;

IR (KBr)1605, 1517, 1209 cm-1; IR (KBr) 1605, 1517, 1209 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 3.53 (s, 3H), 3.82 (s, 3H), 6.45 (dd, J = 7.2 and 2.7 Hz, 1H), 6.47 (s, 1H), 6.73 (s, 1H), 7.08-7.36 (m, 10H), 7.56-7.61 (m, 2H); 1 H NMR (300 MHz, CDCl 3) δ 3.53 (s, 3H), 3.82 (s, 3H), 6.45 (dd, J = 7.2 and 2.7 Hz, 1H), 6.47 (s, 1H), 6.73 (s, 1H), 7.08-7.36 (m, 10H), 7.56-7.61 (m, 2H);

13C NMR (75 MHz, CDCl3) δ 55.50 (2C), 99.69, 104.20, 106.65, 121.57, 122.82, 124.76, 125.03, 125.46, 126.16, 127.32, 127.88, 128.54, 128.99, 133.38, 135.48, 135.95, 155.30, 160.12; 13 C NMR (75 MHz, CDCl 3 ) 隆 55.50 (2C), 99.69, 104.20, 106.65, 121.57, 122.82, 124.76, 125.03, 125.46, 126.16, 127.32, 127.88, 128.54, 128.99, 133.38, 135.48, 135.95, 155.30, 160.12;

ESIMS m/z 356 [M+H]+. ESIMS m / z 356 [M + H] &lt; + &gt;.

Anal. Calcd for C24H21NO2: C, 81.10; H, 5.96; N, 3.94. Anal. Calcd for C 24 H 21 NO 2 : C, 81.10; H, 5.96; N, 3.94.

Found: C, 81.29; H, 5.74; N, 3.95.
Found: C, 81.29; H, 5.74; N, 3.95.

<< 실시예Example 8> 8>

가수분해 화합물 8-2 를 제조한 후, 0.9 당량비의 TFAA를 혼합하고 0 ℃에서 5 분 반응시킨 뒤 상온에서 2 시간 반응 시킨 것을 제외하고는 상기 실시예 1과 동일하게 하여 아래 반응식에서와 같이 디피롤 케톤 화합물 8-3 을 83% 의 수율로 제조하였다. Hydrolysis compound 8-2 was prepared, and TFAA in an equivalent ratio of 0.9 was mixed and reacted at 0 캜 for 5 minutes and then reacted at room temperature for 2 hours. In the same manner as in Example 1, The roll ketone compound 8-3 was prepared in a yield of 83%.

Figure 112014002478358-pat00023
Figure 112014002478358-pat00023

Compound 8-3 : yellow solid, mp > 140 ℃ (dec.); Compound 8-3: yellow solid, mp > 140 [deg.] C (dec.);

IR(KBr) 3424, 1574, 1467, 1270 cm-1; IR (KBr) 3424, 1574, 1467, 1270 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 6.41 (s, 2H), 7.05-7.40 (m, 20H), 9.74 (s, 2H); 1 H NMR (300 MHz, CDCl 3 )? 6.41 (s, 2H), 7.05-7.40 (m, 20H), 9.74 (s, 2H);

13C NMR (75 MHz, CDCl3) δ 109.54, 124.86, 126.69, 127.49, 127.81, 127.85, 128.85, 128.91, 130.89, 133.61, 134.79, 136.49, 175.68; 13 C NMR (75 MHz, CDCl 3) δ 109.54, 124.86, 126.69, 127.49, 127.81, 127.85, 128.85, 128.91, 130.89, 133.61, 134.79, 136.49, 175.68;

ESIMS m/z 465 [M+H]+. ESIMS m / z 465 [M + H] &lt; + &gt;.

Anal. Calcd for C33H24N2O: C, 85.32; H, 5.21; N, 6.03. Anal. Calcd for C 33 H 24 N 2 O: C, 85.32; H, 5.21; N, 6.03.

Found: C, 85.20; H, 5.45; N, 5.87.
Found: C, 85.20; H, 5.45; N, 5.87.

<< 실시예Example 9> 9>

가수분해 화합물 4-2 를 제조한 후, 1,2,4-Triphenyl-1H-pyrrole (2.5 equiv), 0.9 당량의 TFAA를 혼합하고, 0 ℃에서 5 분 반응시킨 뒤 상온에서 2 시간 반응 시킨 것을 제외하고는 상기 실시예 1과 동일하게 하여 아래 반응식에서와 같이 비대칭 디피롤 케톤 화합물 9-3 을 57% 의 수율로 제조하였다. After hydrolysis compound 4-2 was prepared, 1,2,4-triphenyl- 1H- pyrrole (2.5 equiv) and 0.9 equivalent of TFAA were mixed and reacted at 0 ° C for 5 minutes, followed by reaction at room temperature for 2 hours , The asymmetric dipyrrole ketone compound 9-3 was prepared in a yield of 57% as in the following reaction scheme.

Figure 112014002478358-pat00024
Figure 112014002478358-pat00024

Compound 9-3 : yellow solid, mp 76-78 ℃; Compound 9-3: yellow solid, mp 76-78 [deg.] C;

IR (KBr) 1597, 1496, 1455 cm-1; IR (KBr) 1597, 1496, 1455 cm &lt; -1 & gt ;;

1H NMR (300 MHz, CDCl3) δ 1.99 (s, 3H), 5.36 (d, J = 15.9 Hz, 1H), 5.58 (d, J = 15.9 Hz, 1H), 5.63 (s, 1H), 6.04 (s, 1H), 6.87-6.92 (m, 4H), 7.03-7.34 (m, 21H); 1 H NMR (300 MHz, CDCl 3) δ 1.99 (s, 3H), 5.36 (d, J = 15.9 Hz, 1H), 5.58 (d, J = 15.9 Hz, 1H), 5.63 (s, 1H), 6.04 (s, 1 H), 6.87 - 6.92 (m, 4 H), 7.03 - 7.34 (m, 21 H);

13C NMR (75 MHz, CDCl3) δ 12.43, 48.48, 110.67, 110.94, 125.75, 125.95, 126.89, 126.99, 127.03, 127.29, 127.40, 127.84, 128.07, 128.49, 128.76, 128.99, 129.23, 129.29, 131.60, 131.62, 132.35, 134.59, 135.08, 135.75, 136.32, 137.79, 138.09, 138.68, 177.91 (two carbons were overlapped); 13 C NMR (75 MHz, CDCl 3) δ 12.43, 48.48, 110.67, 110.94, 125.75, 125.95, 126.89, 126.99, 127.03, 127.29, 127.40, 127.84, 128.07, 128.49, 128.76, 128.99, 129.23, 129.29, 131.60, 131.62 , 132.35, 134.59, 135.08, 135.75, 136.32, 137.79, 138.09, 138.68, 177.91 (two carbons were overlapped);

ESIMS m/z 569 [M+H]+. ESIMS m / z 569 [M + H] &lt; + &gt;.

Anal. Calcd for C41H32N2O: C, 86.59; H, 5.67; N, 4.93. Anal. Calcd for C 41 H 32 N 2 O: C, 86.59; H, 5.67; N, 4.93.

Found: C, 86.37; H, 5.71; N, 4.69.Found: C, 86.37; H, 5.71; N, 4.69.

Claims (11)

아래 화학식 1 로 표시되는 2-카르복시산 피롤 화합물을 준비하는 제 1 단계;
[화학식 1]
Figure 112014002478358-pat00025

(상기 화학식 1 에서, R1 내지 R4 는 서로 독립적으로 수소, 탄소수 1 내지 10의 알킬기, 탄소수 1 내지 10의 알케닐기, 탄소수 5 내지 10의 아릴기, 탄소수 1 내지 5의 알콕시기로 치환된 탄소수 6 내지 15의 아릴기, 탄소수 3 내지 10의 헤테로 아릴기, 벤질기, 중 어느 하나임)

상기 화학식 1로 표시되는 2-카르복시산 피롤 화합물을 유기 용매에 용해시키고 아래 화학식 2로 표시되는 화합물과 15 ℃ 내지 35 ℃에서 2 시간 내지 24 시간 반응시키는 제 2 단계; 를 포함하는 디피롤 케톤의 제조 방법.
[화학식 2]
Figure 112014002478358-pat00026

(상기 화학식 2 에서, X 는 F, Cl, Br 중 어느 하나임)
A first step of preparing a 2-carboxylic acid pyrrole compound represented by the following formula (1);
[Chemical Formula 1]
Figure 112014002478358-pat00025

(In the above formula 1, R &lt; 1 &gt; To R 4 is independently selected from the group consisting of hydrogen, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 1 to 10 carbon atoms, an aryl group having 5 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms substituted with an alkoxy group having 1 to 5 carbon atoms, A heteroaryl group having 1 to 10 carbon atoms, or a benzyl group)

A second step of dissolving the 2-carboxylate pyrrole compound represented by the formula (1) in an organic solvent and reacting with a compound represented by the following formula (2) at 15 ° C to 35 ° C for 2 to 24 hours; &Lt; / RTI &gt;
(2)
Figure 112014002478358-pat00026

(In the above formula (2), X is any one of F, Cl and Br)
제 1 항에 있어서,
상기 제 2 단계는 아래 화학식 3으로 표시되는 피롤 화합물을 더 포함하는 것을 특징으로 하는 디피롤 케톤의 제조 방법.
[화학식 3]
Figure 112014002478358-pat00027

(상기 화학식 3에서 R5 내지 R8 은 서로 독립적으로 수소, 탄소수 1 내지 10의 알킬기, 탄소수 1 내지 10의 알케닐기, 탄소수 5 내지 10의 아릴기, 탄소수 1 내지 5의 알콕시기로 치환된 탄소수 6 내지 15의 아릴기, 탄소수 3 내지 10의 헤테로 아릴기, 벤질기, 중 어느 하나임)
The method according to claim 1,
Wherein the second step further comprises a pyrrole compound represented by the following general formula (3).
(3)
Figure 112014002478358-pat00027

(Wherein R &lt; 5 &gt; To R 8 is independently selected from the group consisting of hydrogen, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 1 to 10 carbon atoms, an aryl group having 5 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms substituted with an alkoxy group having 1 to 5 carbon atoms, A heteroaryl group having 1 to 10 carbon atoms, or a benzyl group)
제 1 항에 있어서,
상기 유기 용매는 dichloromethane(CH2Cl2), tetrahydrofuran(THF), N,N-dimethylformamide(DMF), acetonitrile(CH3CN), 및 이들의 혼합물에서 선택되는 것인 디피롤 케톤의 제조 방법.
The method according to claim 1,
Wherein the organic solvent is selected from dichloromethane (CH 2 Cl 2 ), tetrahydrofuran (THF), N, N-dimethylformamide (DMF), acetonitrile (CH 3 CN), and mixtures thereof.
제 1 항에 있어서,
상기 화학식 2로 표시되는 화합물은 0.5 내지 2.0 당량비로 혼합되는 것을 특징으로 하는 디피롤 케톤의 제조 방법.
The method according to claim 1,
Wherein the compound represented by Formula 2 is mixed in an equivalent ratio of 0.5 to 2.0.
제 1 항에 있어서,
상기 제 2 단계에서 15 ℃ 내지 35 ℃에서 2 시간 내지 24 시간 반응시키기 이전에 0 내지 5 ℃에서 1 내지 10 분 동안 반응시키는 단계를 더 포함하는 디피롤 케톤의 제조 방법.
The method according to claim 1,
Wherein the reaction is carried out at 0 to 5 DEG C for 1 to 10 minutes before the reaction is carried out at 15 DEG C to 35 DEG C for 2 to 24 hours in the second step.
제 1 항에 있어서,
상기 화학식 1은 아래 화학식 4 및 7 내지 11 에서 선택된 것인 디피롤 케톤의 제조 방법.
Figure 112015106772003-pat00032

Figure 112015106772003-pat00029

Figure 112015106772003-pat00030

The method according to claim 1,
Wherein the formula (1) is selected from the following formulas (4) and (7) to (11).
Figure 112015106772003-pat00032

Figure 112015106772003-pat00029

Figure 112015106772003-pat00030

 제 1 항에 있어서,
상기 화학식 2로 표시되는 화합물은 TFAA(trifluoroacetic anhydride) 인 것을 특징으로 하는 디피롤 케톤의 제조 방법.
The method according to claim 1,
Wherein the compound represented by Formula 2 is TFAA (trifluoroacetic anhydride).
제 1 항에 있어서,
상기 화학식 1로 표시되는 2-카르복시산 피롤 화합물을 준비하는 단계는
tetrahydrofuran(THF), methanol, 및 H2O 가 2:2:1 의 부피비로 혼합된 용매를 준비하는 단계;
상기 용매에 아래 화학식 12로 표시되는 화합물 및 NaOH 또는 KOH 를 혼합하는 단계; 및
상기 혼합 용액을 40 내지 60 ℃ 의 온도에서 36 시간 내지 42 시간 동안 반응시키는 단계; 를 포함하는 것인 디피롤 케톤의 제조 방법.
[화학식 12]
Figure 112015106772003-pat00031

(상기 화학식 12 에서, R1 내지 R4 는 서로 독립적으로 수소, 탄소수 1 내지 10의 알킬기, 탄소수 1 내지 10의 알케닐기, 탄소수 5 내지 10의 아릴기, 탄소수 1 내지 5의 알콕시기로 치환된 탄소수 6 내지 15의 아릴기, 탄소수 3 내지 10의 헤테로 아릴기, 벤질기, 중 어느 하나이고,
R9 는 탄소수 1 내지 10의 알킬기 임)
The method according to claim 1,
The step of preparing the 2-carboxylate pyrrole compound represented by the above formula (1)
preparing a solvent in which tetrahydrofuran (THF), methanol, and H 2 O are mixed in a volume ratio of 2: 2: 1;
Mixing the compound represented by the following formula (12) and NaOH or KOH in the solvent; And
Reacting the mixed solution at a temperature of 40 to 60 DEG C for 36 to 42 hours; &Lt; / RTI &gt;
[Chemical Formula 12]
Figure 112015106772003-pat00031

Wherein R 1 to R 4 independently represent hydrogen, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 1 to 10 carbon atoms, an aryl group having 5 to 10 carbon atoms, an alkoxy group substituted with an alkoxy group having 1 to 5 carbon atoms An aryl group having 6 to 15 carbon atoms, a heteroaryl group having 3 to 10 carbon atoms, or a benzyl group,
And R &lt; 9 &gt; is an alkyl group having 1 to 10 carbon atoms)
제 8 항에 있어서,
상기 NaOH 또는 KOH 는 5 내지 10 당량비로 포함되는 것을 특징으로 하는 디피롤 케톤의 제조 방법.
9. The method of claim 8,
Wherein the NaOH or KOH is contained in an amount of 5 to 10 equivalents.
삭제delete 삭제delete
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Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BESHARA, CORY S. et al., J. Org. Chem. Vol.70, 2005, pp.10607-10610*
HUGGINS, MICHAEL T. et al., Monatshefte fur chemie, Vol.131, 2000, pp.825-838*
LEEN, VOLKER et al., Organic Letters, Vol.14, No.24, 2012, pp.6150-6153*

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