KR101519011B1 - Preparation method of pyrano coumarin derivatives catalyzed by bismuth salts - Google Patents

Preparation method of pyrano coumarin derivatives catalyzed by bismuth salts Download PDF

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KR101519011B1
KR101519011B1 KR1020140001717A KR20140001717A KR101519011B1 KR 101519011 B1 KR101519011 B1 KR 101519011B1 KR 1020140001717 A KR1020140001717 A KR 1020140001717A KR 20140001717 A KR20140001717 A KR 20140001717A KR 101519011 B1 KR101519011 B1 KR 101519011B1
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formula
pyrano
bismuth
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catalyst
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이구연
이필호
김재현
박정민
윤지희
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강원대학교산학협력단
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/16—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of arsenic, antimony, bismuth, vanadium, niobium, tantalum, polonium, chromium, molybdenum, tungsten, manganese, technetium or rhenium
    • B01J23/18—Arsenic, antimony or bismuth
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems

Abstract

The present invention relates to a process for preparing a pyranocoumarin derivative using a bismuth catalyst, which comprises reacting a propargyl alcohol compound and a 4-hydroxy coumarin compound in the presence of a bismuth triflate catalyst to produce a pyrano [3,2- c ] coumarin derivative Is produced. The method of producing the pyranocoumarin derivative according to the present invention can solve the disadvantage that a large amount of byproducts are produced due to the high yield of the pyranocoumarin derivative, and the reaction step is simplified, - C ] coumarin derivative can be produced.

Description

Preparation methods of pyrano coumarin derivatives catalyzed by bismuth salts using bismuth catalysts [

The present invention relates to a process for the preparation of pyrano [3.2- c ] coumarin derivatives using a bismuth catalyst.

The pyranocoumarin derivative is a compound having an oxygen-containing ring and exhibits various physiological activities such as antifungal, insecticide, anti-cancer, anti-HIV, anti-inflammatory, antioxidant and antibacterial activity. In particular, the pyrano [3,2- c ] coumarin derivatives in the form of pyranocoumarin are important structures of natural products exhibiting various physiological activities.

The synthesis of pyrano [3,2- c ] coumarin is synthesized mainly through a cyclization reaction between a 4-hydroxycoumarin derivative and an electrophile which can react with it. In this connection, various synthesis methods of pyrano [3,2- c ] coumarin represented by the following Reaction Scheme 1 are known.

<Reaction Scheme 1>

Figure 112014001440727-pat00001

Stefanie Berger et al. Have disclosed techniques for preparing the desired compound of Scheme 1 in the presence of a ruthenium catalyst using a propargylic alcohol compound ( Tetrahedron Lett . 2010, 51, 6630-6634). However, there is a problem in the selectivity of the reaction site in the reaction in the presence of the ruthenium catalyst, and the reaction yield is low.

Also, in Chinese patent CN101613355A, 4-hydroxycoumarin and 1,3-diaryl-2-alkyne-1-alcohol are dissolved in a solvent and reacted at 50 to 80 ° C for 1 hour under an iodine catalyst. Followed by reaction at 80 to 100 ° C for 8 to 12 hours, adding saturated sodium sulphite again, extracting the organic layer with ethyl acetate, and carrying out column chromatography to produce the desired pyranocoumarin.

However, this method is not easy to handle due to the use of strong sulfuric acid in order to obtain pyrano [3,2- c ] coumarin derivative, which is a target compound, and also causes a large amount of by- ( Tetrahedron 2009 , 65 , 9233-9237).

Thus, the present invention can efficiently synthesize pyrano [3,2- c ] coumarin derivatives by using a simple reaction process without using strong acids, using 4-hydroxy coumarin and a propargyl alcohol derivative as starting materials, And a method for producing the pyranocoumarin derivative using the bismuth catalyst capable of improving the yield by inhibiting the reaction.

In order to accomplish the above object, the present invention provides a process for preparing a compound represented by the following formula (1) by reacting a propargyl alcohol compound represented by the following formula (2) and a 4-hydroxycoumarin compound represented by the following formula (3) in the presence of a bismuth triflate catalyst, (2, 3- c ) coumarin derivative represented by the following general formula (1).

[Chemical Formula 1]

Figure 112014001440727-pat00002

(In the formula 1, R 1, and R 2 are each a methyl, nitro group consisting of hydrogen, halogen, triple independently, an alkoxy group having 1 to 5 carbon atoms or alkyl having 1 to 5).

(2)

Figure 112014001440727-pat00003

Wherein R 2 is hydrogen, halogen, trifluoromethyl, nitro, alkyl of 1 to 5 carbon atoms or alkoxy of 1 to 5 carbon atoms.

(3)

Figure 112014001440727-pat00004

(R 1, in formula (I) is methyl, nitro group consisting of hydrogen, halogen, triple, alkoxy having 1 to 5 carbon atoms or alkyl having 1 to 5).

The 4-hydroxy coumarin compound represented by the formula (3) may be added in an amount of 0.7 to 1.3 equivalents based on 1 equivalent of the propargyl alcohol compound represented by the formula (2).

The bismuth catalyst may be bismuth triflate.

The bismuth catalyst is preferably used in an amount of 0.01 to 1 equivalent based on 1 equivalent of the propargyl alcohol compound represented by the formula (2).

The reaction may be carried out in the presence of at least one solvent selected from the group consisting of chlorobenzene, dichloroethane, toluene, tetrahydrofuran, and nitromethane.

The reaction can be carried out at a temperature ranging from 90 to 110 ° C.

The pyrano [3,2- c ] coumarin derivative represented by the above formula (1)

Figure 112014001440727-pat00005
,
Figure 112014001440727-pat00006
,
Figure 112014001440727-pat00007
,
Figure 112014001440727-pat00008
,
Figure 112014001440727-pat00009
,
Figure 112014001440727-pat00010
,
Figure 112014001440727-pat00011
,
Figure 112014001440727-pat00012
or
Figure 112014001440727-pat00013
Lt; / RTI &gt;

In the method of producing the pyranoquarinine derivative according to the present invention, when the propargylic alcohol and 4-hydroxy coumarin are reacted with each other under the bismuth catalyst, it is possible to compensate the disadvantage that the byproduct is generated in a large amount and the yield is lowered In addition, the pyrano [3,2- C ] coumarin derivative can be produced with high yield by simplifying the reaction step.

Hereinafter, the present invention will be described in detail.

In the present invention, in order to produce a pyrano [3,2- c ] coumarin derivative represented by the following formula 1, a propargyl alcohol compound represented by the following formula 2 and a 4-hydroxycoumarin compound represented by the following formula 3 are reacted with bismuth tri In the presence of a plate catalyst.

[Chemical Formula 1]

Figure 112014001440727-pat00014

(In the formula 1, R 1, and R 2 are each a methyl, nitro group consisting of hydrogen, halogen, triple independently, an alkoxy group having 1 to 5 carbon atoms or alkyl having 1 to 5).

(2)

Figure 112014001440727-pat00015

Wherein R 2 is hydrogen, halogen, trifluoromethyl, nitro, alkyl of 1 to 5 carbon atoms or alkoxy of 1 to 5 carbon atoms.

(3)

Figure 112014001440727-pat00016

(R 1, in formula (I) is methyl, nitro group consisting of hydrogen, halogen, triple, alkoxy having 1 to 5 carbon atoms or alkyl having 1 to 5).

In order to prepare the pyrano [3,2- c ] coumarin derivative represented by Formula 1 above, the present invention uses the propargyl alcohol compound represented by Formula 2 and the 4-hydroxycoumarin compound represented by Formula 3 .

In the propargyl alcohol compound represented by the general formula (2), R 2 is hydrogen, halogen, trifluoromethyl, nitro, alkyl of 1 to 5 carbon atoms, or alkoxy of 1 to 5 carbon atoms. Preferably R 2 may be a methyl, nitro group consisting of hydrogen, halogen, triple, methyl or methoxy.

In the 4-hydroxycoumarin compound represented by Formula 3, R 1 is hydrogen, halogen, trifluoromethyl, nitro, alkyl of 1 to 5 carbon atoms, or alkoxy of 1 to 5 carbon atoms. Preferably R &lt; 1 &gt; is hydrogen or methyl.

The 4-hydroxy coumarin compound represented by the formula (3) may be added in an amount of 0.7 to 1.3 equivalents, preferably 0.8 to 1.2 equivalents based on 1 equivalent of the propargyl alcohol compound represented by the formula (2). When the amount of the 4-hydroxy coumarin compound represented by formula (3) is less than 0.7 equivalent based on 1 equivalent of the propargyl alcohol compound represented by formula (2), there is a disadvantage in that the reaction yield is lowered due to insufficient reaction, The reaction yield can not be obtained any more.

At this time, in the present invention, a bismuth catalyst is used as a reaction catalyst. The bismuth catalyst is very cheap as compared with the catalyst used in the conventional production of pyranocoumarin derivatives and has advantages of high reaction yield due to the suppression of side reaction because strong acid is not used and advantageous in particular that the reaction process is simple.

The bismuth catalyst is not necessarily limited, but bismuth triflate can be preferably used.

The bismuth catalyst is preferably used in the range of 0.01 to 1 equivalent, preferably 0.05 to 0.2 equivalent based on 1 equivalent of the propargyl alcohol compound represented by the formula (2). When the amount of the bismuth catalyst is less than 0.01 equivalent, the reaction yield is low. When the amount of the bismuth catalyst is more than 1 equivalent, the reaction yield can not be further improved. It is preferably used in an amount of 0.01 to 1 equivalent based on 1 equivalent of propargyl alcohol compound.

The reaction can be carried out in the presence of a solvent. The solvent is not particularly limited as long as it is a solvent that dissolves the reactants and does not inhibit the reaction. Specifically, the solvent may be at least one selected from the group consisting of chlorobenzene, dichloroethane, toluene, tetrahydrofuran, and nitromethane. Considering the double reaction rate and yield, nitromethane is preferred.

The reaction may vary somewhat depending on the kind of the starting material, but is preferably carried out in a temperature range of 90 to 110 ° C, preferably 95 to 105 ° C. There is a problem that the yield may be lowered when the reaction temperature is out of the above range.

The reaction time is suitably adjusted according to the starting material, the kind and amount of the solvent, the reaction temperature, and the like. For example, it is preferable to confirm that the propargyl alcohol compound of formula (2) is exhausted through TLC or the like, and that the reaction is completed after confirming that the intermediate before cyclization has been consumed.

When the reaction is completed, the solvent can be distilled off under reduced pressure, and the desired product can be separated and purified through a conventional method such as column chromatography.

As described above, the pyrano [3,2-b] pyridine represented by Formula 1, which can be prepared by reacting the propargyl alcohol compound represented by Formula 2 and the 4-hydroxycoumarin compound represented by Formula 3 in the presence of a bismuth catalyst, c ] coumarin derivatives are more specifically

Figure 112014001440727-pat00017
,
Figure 112014001440727-pat00018
,
Figure 112014001440727-pat00019
,
Figure 112014001440727-pat00020
,
Figure 112014001440727-pat00021
,
Figure 112014001440727-pat00022
,
Figure 112014001440727-pat00023
,
Figure 112014001440727-pat00024
or
Figure 112014001440727-pat00025
Lt; / RTI &gt;

Hereinafter, the structure of the present invention will be described in more detail with reference to examples. However, the following examples are provided to aid understanding of the present invention, and the scope of the present invention is not limited thereto.

Example  1: 2,4- Diphenyl -4 H - Pyrano [3,2- c ] Chromen 5-one (2,4- Di - phenyl -4 H pyrano [3,2- c ] chromen-5-one)

The test tube was charged with 4-hydroxy coumarin (58.37 mg, 0.36 mmol) and 1,3-diphenyl-2-propyne (1.5 mL) in the presence of bismuth triflate (19.68 mg, 0.03 mmol) -1-ol (62.47 mg, 0.3 mmol) were mixed and stirred at 100 ° C. After 8 hours, the solvent was removed after the celite filter, and the resultant was purified by column chromatography to obtain the title compound, 2,4-diphenyl- 4H -pyrano [3,2- c ] chromen-

Figure 112014001440727-pat00026
, 83.51 mg, 79%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 8.03-8.01 (m, 1H), 7.74-7.71 (m, 2H), 7.59-7.54 (m, 1H), 7.47-7.29 (m, 9H ), 7.25-7.21 (m, 1H), 5.85 (d, J = 4.8 Hz, 1H), 4.71 (d, J = 5.2 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ161.5, 155.8, 152.8, 146.9, 143.6, 132.6, 132.0, 129.3, 128.7, 127.3, 124.7, 124.2, 122.7, 116.9, 114.6, 103.8, 103.7, 36.6.

Example  2: 2- Phenyl -4- Oso - Taurylpyrano [3,2- c ] Chromen -5 (4 H ) -One (2- phenyl -4- o -tolylpyrano [3,2- c ] chromen-5 (4 H ) -one) manufacture

The test tube was charged with 4-hydroxy coumarin (58.37 mg, 0.36 mmol) and 3-phenyl-1-ortho-tolylpro- bipyridine in the presence of bismuth triflate (19.68 mg, 0.03 mmol) 2-pin-1-ol (66.68 mg, 0.3 mmol) was mixed and stirred at 100 ° C. After 6 hours, the reaction mixture was filtered through a Celite filter, and the solvent was distilled off to obtain 4- (4-methoxy-phenyl) -2-phenyl- 4H -pyrano [3,2- c ] Chromen-5-one (

Figure 112014001440727-pat00027
, 58.25 mg, 53%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 8.05 (m, 1H), 7.72-7.69 (m, 2H), 7.61-7.57 (m, 1H), 7.46-7.35 (m, 5H), 7.20-7.16 (m, 2H), 7.13-7.10 (m, 2H), 5.78 (d, J = 4.0 Hz, 1H), 4.95 (d, J = 4.0 Hz, 1H); 13 C NMR (100 MHz, CDCl 3) δ 161.4, 156.2, 152.7, 146.4, 142.3, 135.6, 132.7, 132.0, 130.6, 129.2, 128.8, 128.6, 126.9, 126.6, 124.6, 124.2, 122.6, 116.8, 114.5, 103.7 , 103.4, 32.6, 19.6.

Example  3: 4- (4- ( Trifluoromethyl ) Phenyl )-2- Phenylpyrano [3,2- c ] Chromen -5 (4 H ) -One (4- (4- ( trifluoromethyl ) phenyl )-2- phenylpyrano [3,2- c ] chromen -5 (4 H ) -one) manufacture

The test tube was charged with 4-hydroxy coumarin (58.37 mg, 0.36 mmol) and 1- (4- (trifluoromethyl) pyridine) in the presence of bismuth triflate (19.68 mg, 0.03 mmol) Phenyl) -3-phenylprop-2-one-ol (82.87 mg, 0.3 mmol) were mixed and stirred at 100 ° C. If after 11-hour reaction was completed, celite filter (4- (trifluoromethyl) phenyl), then after separation by column chromatography to give the title compound, 4 to the removal of solvent-2-phenyl-pyrano [3,2- c] Chromen-5 ( 4H ) -one (

Figure 112014001440727-pat00028
, 113.50 mg, 90%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 8.05-8.03 (m, 2H), 7.75-7.72 (m, 2H), 7.62-7.53 (m, 5H), 7.49-7.35 (m, 5H ), 5.82 (d, J = 4.0 Hz, 1H), 4.80 (d, J = 4.0 Hz, 1H); 13 C NMR (100 MHz, CDCl 3) δ 161.4, 156.1, 152.8, 147.4, 132.4, 132.3, 129.6, 129.3, 129.0, 128.9, 128.8, 125.7, 125.6, 125.6, 125.5, 125.5, 124.7, 124.4, 122.7, 116.9 , 114.3, 102.9, 102.8, 36.6.

Example  4: 4- (3- Chlorophenyl )-2- Phenylpyrano [3,2- c ] Chromen -5 (4 H ) -One (4- (3-chlorophenyl) -2-phenylpyrano [3,2- c ] chromen-5 (4 H ) -one) manufacture

(58.37 mg, 0.36 mmol) and 1- (3- (chlorophenyl) -3, 4-dihydroxyquinoline in the presence of bismuth triflate (19.68 mg, 0.03 mmol) (72.81 mg, 0.3 mmol), and the mixture was stirred at 100 ° C. After completion of the reaction for 8 hours, the reaction mixture was filtered through a Celite filter, and the filtrate was subjected to column chromatography The compound 4- (3-chlorophenyl) -2-phenylpyrano [3,2- c ] chromen-5 (4H)

Figure 112014001440727-pat00029
, 91.67 mg, 79%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 8.04-8.02 (m, 1H), 7.75-7.72 (m, 2H), 7.61-7.57 (m, 1H), 7.52-7.31 (m, 7H ), 7.27-7.19 (m, 2H), 5.81 (d, J = 4.0 Hz, 1H), 4.71 (d, J = 4.0 Hz, 1H); 13 C NMR (100 MHz, CDCl 3) δ 161.4, 156.0, 152.8, 147.2, 145.6, 134.6, 132.4, 132.3, 129.9, 129.5, 128.8, 128.6, 127.5, 124.7, 124.3, 122.8, 116.9, 114.4, 103.1, 103.0 , 36.5.

Example  5: 4- (2- Bromophenyl )-2- Phenylpyrano [3,2- c ] Chromen -5 (4 H ) -One (4- (2-bromophenyl) -2-phenylpyrano [3,2- c ] chromen-5 (4 H ) -one) manufacture

The test tube was charged with 4-hydroxy coumarin (58.37 mg, 0.36 mmol) and 1- (2- (bromophenyl) - (82.23 mg, 0.3 mmol), and the mixture was stirred at 100 ° C. After completion of the reaction for 6 hours, the reaction mixture was filtered through a Celite filter, and the filtrate was separated by column chromatography The title compound, 4- (2-bromophenyl) -2-phenylpyrano [3,2- c ] chromen-5 ( 4H )

Figure 112014001440727-pat00030
, 90.56 mg, 70%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 8.05-8.03 (m, 1H), 7.71-7.68 (m, 2H), 7.63-7.58 (m, 2H), 7.45-7.38 (m, 5H ), 7.25-7.17 (m, 2H), 7.11-7.06 (m, 1H), 5.89 (d, J = 4.0 Hz, 1H), 5.23 (d, J = 4.0 Hz, 1H); 13 C NMR (100 MHz, CDCl 3) δ 161.1, 157.2, 152.9, 146.7, 142.4, 133.2, 132.5, 132.3, 129.6, 129.3, 128.7, 128.6, 128.1, 124.7, 124.3, 123.3, 122.8, 116.9, 114.3, 102.2 , 102.1 36.4.

Example  6: 4- (3- Nitrophenyl )-2- Phenylpyrano [3,2- c ] Chromen -5 (4 H ) -One (4- (3-nitrophenyl) -2-phenylpyrano [3,2- c ] chromen-5 (4 H ) -one) manufacture

(58.37 mg, 0.36 mmol) and l- (3- (nitrophenyl) - (4-hydroxyphenyl) -methyl) quinoline in the presence of bismuth triflate (19.68 mg, 0.03 mmol) (75.97 mg, 0.3 mmol), and the mixture was stirred at 100 ° C. After completion of the reaction for 8 hours, the reaction mixture was filtered through a Celite filter, followed by separation by column chromatography Phenylpyrano [3,2- c ] chromen-5 ( 4H ) -one (

Figure 112014001440727-pat00031
, 78.68 mg, 66%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 8.27 (s, 1H), 8.12 (dd, J 1 = 1.04 Hz, J 2 = 7.2Hz, 1H), 8.06 ( d, J = 7.8Hz, 1H), 7.82 (d, J = 7.7Hz, 1H), 7.77 (d, J = 7.8Hz, 2H), 7.63 (t, J = 7.3 1H), 7.54-7.41 (m, 5H), 7.38-7.36 (m, 1H), 5.82 (d, J = 4.7 Hz, 1H), 4.86 (d, J = 4.7 Hz, 1H); 13 C NMR (100 MHz, CDCl 3) δ 161.3, 156.3, 152.8, 148.6, 147.7, 145.6, 134.8, 132.5, 132.1, 129.7, 129.5, 128.8, 124.8, 124.4, 123.4, 122.9, 122.4, 116.9, 114.2, 102.4 , 102.3, 36.6.

Example  7: 7- methyl -2,4- Diphenylpyrano [3,2- c ] Chromen -5 (4 H ) -One (7- methyl -2,4-diphenylpyrano [3,2- c ] chromen-5 (4 H ) -one) manufacture

The test tube was charged with 4-hydroxy-8-methyl-coumarin (63.42 mg, 0.36 mmol) in the presence of bismuth triflate (19.68 mg, 0.03 mmol) -2-propyn-1-ol (62.47 mg, 0.3 mmol) were mixed and stirred at 100 ° C. After 6 hours, the reaction mixture was filtered through a Celite filter, and the solvent was removed by column chromatography to obtain 7-methyl-2,4-diphenylpyrano [3,2- c ] chromen-5 ( 4H ) (

Figure 112014001440727-pat00032
, 79.14 mg, 72%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 7.87-7.84 (m, 1H), 7.74-7.71 (m, 2H), 7.46-7.37 (m, 6H), 7.34-7.19 (m, 4H ), 5.84 (d, J = 4.0 Hz, 1H), 4.72 (d, J = 4.0 Hz, 1H), 2.42 (s, 3H); 13 C NMR (100 MHz, CDCl 3) δ 162.6, 161.5, 155.9, 151.1, 147.0, 143.7, 133.2, 132.7, 129.2, 128.7, 128.6, 128.5, 127.2, 126.3, 124.7, 123.7, 120.3, 114.3, 103.7, 103.4 , 36.6, 15.7.

Example  8: 9- methyl -2,4- Diphenylpyrano [3,2- c ] Chromen -5 (4 H ) -On (9- methyl -2,4-diphenylpyrano [3,2- c ] chromen-5 (4 H ) -one) manufacture

The test tube was charged with 4-hydroxy-6-methyl-coumarin (63.42 mg, 0.36 mmol) in the presence of bismuth triflate (19.68 mg, 0.03 mmol) -2-propyn-1-ol (62.47 mg, 0.3 mmol) were mixed and stirred at 100 ° C. After 6 hours, the reaction mixture was filtered through a Celite filter, and the solvent was removed by column chromatography to obtain 9-methyl-2,4-diphenylpyrano [3,2- c ] chromen-5 ( 4H ) (

Figure 112014001440727-pat00033
, 71.44 mg, 65%).

1 H NMR (400 MHz, CDCl 3, 293 K, TMS) δ 7.76-7.72 (m, 3H), 7.48-7.31 (m, 8H), 7.25-7.20 (m, 2H), 5.83 (d, J = 4.0 Hz, 1H), 4.70 (d , J = 4.0 Hz, 1H), 2.48 (s, 3H) 13 C NMR (100 MHz, CDCl 3) δ 161.7, 155.8, 151.0, 146.9, 143.7, 134.0, 133.1, 132.7, 129.3, 128.9, 128.7, 128.5, 127.2, 124.7, 122.3, 116.6, 114.2, 103.8, 103.6, 103.4, 36.6, 30.9, 21.1.

As shown in the above examples, the production method of the pyrano coumarin derivative according to the present invention is characterized in that, when a strong acid such as propargyl alcohol and 4-hydroxy coumarin is reacted under a bismuth catalyst, a large amount of by- But also the pyrano [3,2- c ] coumarin derivative represented by the formula (1) can be produced with a high yield by simplifying the reaction step.

For example, according to the first embodiment of the prior Chinese Patent Publication CN101613355A with iodine and strong acid 2,4-diphenyl -4 H - pyrano [3,2- c]chromen-5-one (

Figure 112014001440727-pat00034
) Yield is 65% or, according to a first embodiment of the present invention, 2,4-H of phenyl -4-pyrano [3,2- c] chromen-5-one yield is significantly increased as 79% of The results are shown in Fig.

Claims (7)

Reacting a propargyl alcohol compound represented by the following formula (2) and a 4-hydroxycoumarin compound represented by the following formula (3) in a nitromethane solvent in the presence of a bismuth triflate catalyst to obtain a pyrano [3, 2- c ] coumarin derivative of formula (I).
[Chemical Formula 1]
Figure 112015034188880-pat00035

(Wherein R 1 is H and R 2 is CH 3 , CF 3 or NO 2 )
(2)
Figure 112015034188880-pat00036

(In the formula 2, R 2 is CH 3 , CF 3 or NO 2 )
(3)
Figure 112015034188880-pat00037

(In the above formula (3), R &lt; 1 &gt; is H) The method according to claim 1,
Wherein the 4-hydroxycoumarin compound represented by Formula 3 is added in an amount of 0.7 to 1.3 equivalents based on 1 equivalent of the propargyl alcohol compound represented by Formula 2. The method for producing a pyranocoumarin derivative using the bismuth catalyst . delete The method according to claim 1,
Wherein the bismuth catalyst is used in an amount of 0.01 to 1 equivalent per 1 equivalent of the propargyl alcohol compound represented by the formula (2). delete The method according to claim 1,
Wherein the reaction is carried out at a temperature ranging from 90 to 110 &lt; 0 &gt; C. The method according to claim 1,
The pyrano [3,2- c ] coumarin derivative represented by the above formula (1)
Figure 112015034188880-pat00039
,
Figure 112015034188880-pat00040
, or
Figure 112015034188880-pat00044
&Lt; / RTI &gt; wherein the bismuth-containing catalyst is a bismuth-based catalyst.
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Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Tetrahedron Letters, 2010, vol51. pp.6630-6634 *
Tetrahedron Letters, 2010, vol51. pp.6630-6634*

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