CN112517060A - Catalyst, application and synthesis method of 4-hydroxycoumarin derivative - Google Patents
Catalyst, application and synthesis method of 4-hydroxycoumarin derivative Download PDFInfo
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- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
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- B01J31/0285—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre also containing elements or functional groups covered by B01J31/0201 - B01J31/0274
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- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
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Abstract
The invention relates to a synthetic method of a 4-hydroxycoumarin derivative. The invention provides a synthesis method of 4-hydroxycoumarin derivatives, which takes acid functionalized ionic liquid as a catalyst to catalyze reactants to carry out alkylation reaction, thereby synthesizing a series of 4-hydroxycoumarin derivatives; the reactant comprises a 4-hydroxycoumarin compound as a first reactant and any one of diphenyl alcohols, allyl alcohols, propargyl alcohols and benzyl alcohols as a second reactant. The catalyst in the invention adopts acid functionalized ionic liquid, thus avoiding the defects of high reaction temperature, long reaction time, harsh reaction conditions, complex and difficult subsequent treatment and the like in the prior art; the adopted catalyst has high catalytic activity, small using amount and low catalyst corrosivity; the reaction conditions are milder and more environment-friendly, and the application range of the substrate is wide; the product selectivity is good in the reaction process, the controllability is strong, the yield of the product is high and can reach 99% at most.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis of organic matters, and particularly relates to an acid-functionalized ionic liquid as a catalyst, application of the catalyst, and a method for synthesizing 4-hydroxycoumarin derivatives by using the catalyst.
Background
The construction of the C-C bond is one of important research contents in the field of organic synthesis, and has important application value in theoretical research and industrial and agricultural production. Alcohol is used as a common reactant, is usually used for constructing C-C bonds due to the characteristics of environmental friendliness and universality, is synthesized into 4-hydroxycoumarin derivatives through alkylation of alcohol, has wide biological activity, and has important application in the fields of agriculture and medicine. At present, common catalytic systems for synthesizing 4-hydroxycoumarin derivatives by alkylation of alcohols are as follows:
Fe(ClO4)3·H2O(Tetrahedron,2010,66,2995-3003),Al(OTf)3(Synlett,2015,26,745-750),Bi(NO3)3·5H2O(TetrahedronLett.,2011,52,6859-6864),Yb(OTf)3(Tetrahedron,2007,63,11636-11643),I2(Tetrahedron,2009,65,9233-9237),TMSOTf(TetrahedronLett.,2010,51,5454-5458),AmberliteIR-120(Tetrahedron,2008,64,11666-11672),Pd(OAc)2/PPh3(Tetrahedron,2008,64,1204-1212),RuCl2[PPh3]3(New.J.Chem.,2014,38,1794-1801)。
most of the catalytic systems involve metal, transition metal, halogen elements and strong acid, and have the disadvantages of relatively high price, poor environmental friendliness and complex and difficult subsequent treatment. Meanwhile, most of the existing catalytic systems have many defects, and industrial application is difficult to realize, such as long reaction time, high temperature, harsh reaction conditions and large consumption of reaction solvent, which not only can cause harm to human bodies, but also can cause serious pollution to the environment. In addition, the catalyst has certain corrosivity, so the catalyst is difficult to recycle, and the production cost is higher. Therefore, the development of a green and environment-friendly catalyst with mild reaction conditions, high reaction efficiency, wide application range and high environmental friendliness is urgently needed.
The ionic liquid has raised research hot tide as an environment-friendly solvent which has stable property, good dissolving property, designable and adjustable acid sites and can be reused, is also called as a 'green designer solvent', and other excellent properties of the ionic liquid are still further developed and utilized. The application of ionic liquid in catalytic reaction starts in 1972, then enters a peak in the late century, and a large amount of ionic liquid is synthesized and applied to some catalytic reactions to replace volatile and toxic organic solvents. The ionic liquid has designability, and can serve as a solvent and a catalyst in a reaction through the functional design of cations or anions, so that the ionic liquid has the advantages of homogeneous reaction, two-phase separation, simple operation, repeated recycling, environmental protection and high catalytic efficiency.
In the scheme, the defects of using metal, transition metal, halogen elements, strong acid or catalysts with strong corrosivity and the like exist, or the defects of high reaction temperature, long reaction time, harsh reaction conditions, complex subsequent treatment and the like exist, and in view of the technical difficulty or the defects, improvement is needed, and the method capable of effectively overcoming the defects is invented.
Disclosure of Invention
In order to solve the technical problems, the invention improves and provides an acid functionalized ionic liquid as a catalyst; also provides a method for synthesizing the 4-hydroxycoumarin derivative by using the acid functionalized ionic liquid as a catalyst; according to the invention, the alkylation reaction of 4-hydroxycoumarin and alcohol is catalyzed by the acid functionalized ionic liquid under mild conditions, so that the 4-hydroxycoumarin derivative is generated, the target product has good selectivity and strong controllability, the reactant, the product and the catalyst are easy to separate, and the catalyst can be recycled.
The invention provides a synthesis method of 4-hydroxycoumarin derivatives, which comprises the following steps: taking acid functionalized ionic liquid as a catalyst, and catalyzing reactants to perform alkylation reaction to synthesize the 4-hydroxycoumarin derivative;
the reactants comprise a first reactant and a second reactant, wherein the first reactant is a 4-hydroxycoumarin compound, and the second reactant is any one of diphenyl alcohols, allyl alcohols, propargyl alcohols and benzyl alcohols.
The route of the above synthetic method can be represented as:
wherein R is1Is fluorine, chlorine, bromine, alkyl or hydrogen;
R2is aryl, benzyl, alkyl or hydrogen;
R3aryl, benzyl, alkyl or hydrogen.
In the synthesis method, the catalyst is selected from acidic ionic liquid (acidic functionalized ionic liquid), is metal-free and environment-friendly; the catalyst has high catalytic activity and small using amount; the operation is simple, and the corrosion of the catalyst is low; the reaction condition is mild, and the application range of the substrate is wide; the product has good selectivity and strong controllability; the reactants, the products and the catalyst are easy to separate, and the catalyst can be recycled.
In the above synthesis method, the cation of the acidic functionalized ionic liquid is selected from imidazole cation, piperidine cation, pyridine cation, pyrrolidine cation, morpholine cation or thiomorpholine cation; the anion of the functionalized ionic liquid is selected from hydrogen sulfate, p-toluenesulfonate, methane sulfonate or trifluoromethanesulfonate.
The catalyst preferably has a formula selected from:
wherein, X-Selected from Hydrogen Sulfate (HSO)4 -) P-toluenesulfonate (OTS)-) Methane sulfonate (CH)3SO3) Or trifluoromethanesulfonic acid (OTf)-). The catalyst is a key protection content of the invention; in addition, will be as followsThe catalyst is applied to synthesizing the 4-hydroxycoumarin derivative, and is also the content to be protected in the invention.
X-Selected from any one of bisulfate, p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate.
The structural formula and abbreviation of the catalyst are specifically shown as follows:
Preferably, the 4-hydroxycoumarin compound is selected from any one of 4-hydroxycoumarin, 4-hydroxy-7-methylcoumarin, 4-hydroxy-7-methoxycoumarin, 4-hydroxy-6-methylcoumarin, 6-fluoro-4-hydroxycoumarin, 6-chloro-4-hydroxycoumarin, and 6-bromo-4-hydroxycoumarin, but is not limited to the above;
preferably, the diphenyl alcohol is selected from any one of benzhydrol, 4-methylbenzyl alcohol, 2-methylbenzyl alcohol, 4-methoxybenzyl alcohol, 4-dimethoxybenzhydrol, 4-fluorobenzyl alcohol, 4-chlorobenzyl alcohol, 4-bromobenzyl alcohol, 4-trifluoromethylbenzhydrol alcohol, 4-dichlorobenzhydrol alcohol and 4-phenylbenzyl alcohol.
The allyl alcohols are preferably (E) -1, 3-diphenyl-2-en-1-ol.
Propargyl alcohols are preferably 1, 3-diphenyl-2-yn-1-ol.
The benzyl alcohol is selected from any one of alpha-phenethyl alcohol and 4-methoxy benzyl alcohol.
The solvent for the alkylation reaction is preferably dimethyl carbonate.
The reaction temperature of the alkylation reaction is 25-100 ℃, and the reaction time is 2-24 h.
The amount of the catalyst is 1-50 mol% of the first reactant. Preferably, the amount of the catalyst is 2-45 mol% of the first reactant; preferably, the amount of the catalyst accounts for 3-40 mol% of the first reactant; preferably, the amount of the catalyst accounts for 3-30 mol% of the first reactant; preferably, the amount of the catalyst accounts for 3-25 mol% of the first reactant; preferably, the amount of the catalyst accounts for 3-15 mol% of the first reactant;
the molar ratio of the first reactant to the second reactant is 1: 1-5; preferably 1: 1.2.
The invention has the beneficial effects that:
(1) the catalyst in the invention adopts acid functionalized ionic liquid, thus avoiding the defects of high reaction temperature, long reaction time, harsh reaction conditions, complex and difficult subsequent treatment and the like caused by using metal, transition metal, halogen element, strong acid or strong corrosive catalyst in the prior art;
(2) the catalyst adopted in the invention has high catalytic activity, small dosage and low catalyst corrosivity;
(3) the reaction conditions are milder and more environment-friendly, and the application range of the substrate is wide;
(4) the product selectivity is good, the controllability is strong, the yield of the product is high and can reach 99 percent to the maximum;
(5) the reactants, the products and the catalyst are easy to separate, and the catalyst can be recycled.
Detailed Description
The present invention will now be further described with reference to specific embodiments in order to enable those skilled in the art to better understand the present invention.
A medicine purchasing manufacturer:
the drugs to which the invention relates are purchased from: shanghai Michelin Biochemical technologies, Inc., Shanghai Annaiji Chemicals, Inc., Bailingwei technologies, Beijing, Aladdin Biochemical technologies, Inc., Kaitong Chemicals, Inc., Tianjin.
The yield calculation method comprises the following steps:
yield calculation was performed with reference to GB/T27417-2017.
Example 1
The preparation method of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 164.5mg, yield 96%.
1H NMR(400MHz,CDCl3)δ7.76–7.69(m,1H),7.53(ddd,J＝8.7,7.4,1.6Hz,1H),7.41–7.34(m,2H),7.33–7.23(m,5H),7.17(q,J＝8.2Hz,4H),6.33(dd,J＝7.4,2.8Hz,1H),5.93(s,1H),2.35(s,3H).13C NMR(101MHz,CDCl3)δ163.2,160.7,152.8,140.1,137.7,137.0,132.1,130.3,129.4,128.8,128.7,127.7,123.9,123.2,116.5,116.0,107.9,47.0,21.1。
Example 2
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 167.8mg, yield 98%.
Example 3
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL of tetrahydrofuran were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 147.4mg, yield 86%.
Example 4
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL of n-hexane were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 135.5mg, yield 79%.
Example 5
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL1, 4-dioxane were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 168.8mg, yield 99%.
Example 6
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL1, 2-dichloroethane were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 167.9mg, yield 98%.
Example 7
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL of toluene were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 164.4mg, yield 96%.
Example 8
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL cyclohexane were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 164.7mg, yield 96%.
Example 9
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (2 mol%, 3.7mg),2.0mL acetonitrile were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 143.8mg, yield 84%.
Example 10
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL acetonitrile were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 161.3mg, yield 94%.
Example 11
The preparation of 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BspD ] [ OTf ] (10 mol%, 18.2mg),2.0mL acetonitrile were placed in a dry reaction flask at 80 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 164.7mg, yield 96%.
Example 12
The preparation of 4-hydroxy-3- (phenyl (o-tolyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 2-methylbenzyl alcohol (0.6mmol,119.0mg) as well as [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 8h with magnetic stirring. After the reaction, column chromatography was performed (silica gel column; eluent: petroleum ether) to give pure 4-hydroxy-3- (phenyl (o-tolyl) methyl) -2H-pyran-2-one, 133.7mg, in 78% yield.
1H NMR(400MHz,CDCl3)δ7.72(d,J＝7.9Hz,1H),7.54(dd,J＝11.4,4.2Hz,1H),7.34(ddd,J＝21.2,15.9,7.0Hz,6H),7.20(dd,J＝17.4,9.5Hz,3H),7.02(d,J＝7.6Hz,1H),6.37(s,1H),6.01(s,1H),2.32(s,3H).13C NMR(101MHz,CDCl3)δ163.0,161.0,152.7,139.8,138.6,138.1,132.1,131.7,129.5,128.8,128.0,127.8,127.4,127.0,123.9,123.2,116.5,115.8,106.5,45.2,19.7。
Example 13
The preparation of 4-hydroxy-3- ((4-methoxyphenyl) (phenyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methoxybenzyl alcohol (0.6mmol,128.6mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- ((4-methoxyphenyl) (phenyl) methyl) -2H-pyran-2-one, 175.8mg, 98% yield.
1H NMR(600MHz,CDCl3)δ7.73(d,J＝7.9Hz,1H),7.53(t,J＝7.8Hz,1H),7.38(t,J＝7.4Hz,2H),7.34–7.30(m,2H),7.28(d,J＝8.1Hz,3H),7.18(d,J＝8.5Hz,2H),6.91(d,J＝8.7Hz,2H),6.31(s,1H),5.91(s,1H),3.81(s,3H).13C NMR(151MHz,CDCl3)δ163.3,160.6,159.2,152.7,140.2,132.1,131.7,129.9,129.4,128.7,127.7,123.9,123.2,116.5,116.0,114.9,107.9,55.3,46.6。
Example 14
The preparation method of 3- (bis (4-methoxyphenyl) methyl) -4-hydroxy-2H-pyran-2-ketone comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4, 4-dimethoxybenzhydrol (0.6mmol,128.6mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3- (bis (4-methoxyphenyl) methyl) -4-hydroxy-2H-pyran-2-one, 192.5mg, 99% yield.
1H NMR(400MHz,CDCl3)δ7.73(d,J＝7.8Hz,1H),7.53(t,J＝7.7Hz,1H),7.33–7.15(m,6H),6.90(d,J＝8.5Hz,4H),6.39(s,1H),5.84(s,1H),3.81(s,6H).13C NMR(101MHz,CDCl3)δ163.2,160.5,159.1,152.7,132.01,132.0,129.8,123.9,123.1,116.4,116.0,114.8,113.4,108.0,55.3,45.8。
Example 15
The preparation method of the 3-benzhydryl-4-hydroxy-2H-pyran-2-ketone comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and benzhydrol (0.6mmol,110.5mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 8h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3-Diphenylmethyl-4-hydroxy-2H-pyran-2-one, 157.8mg, yield 96%.
1H NMR(400MHz,CDCl3)δ7.73(dd,J＝8.0,1.5Hz,1H),7.54(ddd,J＝8.8,7.4,1.6Hz,1H),7.42–7.36(m,4H),7.36–7.30(m,3H),7.30–7.26(m,5H),6.22(s,1H),5.99(s,1H).13C NMR(101MHz,CDCl3)δ163.2,152.7,139.9,132.2,129.5,128.8,127.9,123.9,123.2,116.5,115.9,107.7,107.1,47.4。
Example 16
The preparation method of 3- ((4-fluorophenyl) (phenyl) methyl) -4-hydroxy-2H-pyran-2-ketone comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-fluorobenzyl alcohol (0.6mmol,121.2mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 12h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3- ((4-fluorophenyl) (phenyl) methyl) -4-hydroxy-2H-pyran-2-one, 159.5mg, 92% yield.
1H NMR(600MHz,CDCl3)δ7.73(dd,J＝7.9,1.3Hz,1H),7.57–7.52(m,1H),7.40(t,J＝7.4Hz,2H),7.34(dd,J＝13.1,7.6Hz,2H),7.25(s,5H),7.07(t,J＝8.6Hz,2H),6.19(s,1H),5.95(s,1H).13C NMR(151MHz,CDCl3)δ163.1,161.3,160.6,152.7,140.0,135.3,132.3,130.5,130.4,129.7,128.6,128.1,124.0,123.2,116.3(t,J＝21.2Hz),115.8,107.6,46.6。
Example 17
The preparation method of 3- ((4-chlorphenyl) (phenyl) methyl) -4-hydroxy-2H-pyran-2-ketone comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-chlorobenzhydrol (0.6mmol,131.2mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 12h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3- ((4-chlorophenyl) (phenyl) methyl) -4-hydroxy-2H-pyran-2-one, 147.1mg, 81% yield.
1H NMR(400MHz,CDCl3)δ7.74(d,J＝7.9Hz,1H),7.55(t,J＝7.8Hz,1H),7.36(dt,J＝15.5,7.4Hz,6H),7.28–7.20(m,5H),6.30(s,1H),5.94(s,1H).13C NMR(101MHz,CDCl3)δ163.1,160.8,152.7,139.8,138.2,133.5,132.3,130.2,129.7,129.4,128.6,128.2,124.0,123.2,116.5,115.8,107.3,46.7。
Example 18
The preparation of 3- ((4-bromophenyl) (phenyl) methyl) -4-hydroxy-2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-bromobenzyl alcohol (0.6mmol,157.9mg) as well as [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 12h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3- ((4-bromophenyl) (phenyl) methyl) -4-hydroxy-2H-pyran-2-one, 134.8mg, 66% yield.
1H NMR(400MHz,CDCl3)δ7.73(d,J＝7.9Hz,1H),7.58–7.47(m,3H),7.37(dt,J＝19.2,7.9Hz,4H),7.25(d,J＝8.7Hz,3H),7.17(d,J＝7.6Hz,2H),6.19(s,1H),5.93(s,1H).13C NMR(101MHz,CDCl3)δ163.1,160.7,152.7,139.7,138.7,132.4,132.3,130.5,129.8,128.6,128.2,124.0,123.2,121.7,116.5,115.8,107.3,46.8。
Example 19
The preparation of 4-hydroxy-3- (phenyl (4- (trifluoromethyl) phenyl) methyl) -2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-trifluoromethylbenzhydrol (0.6mmol,151.3mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 80 ℃ and reacted for 4h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (phenyl (4- (trifluoromethyl) phenyl) methyl) -2H-pyran-2-one, 149.7mg, 81% yield.
1H NMR(400MHz,CDCl3)δ7.75(d,J＝7.9Hz,1H),7.63(d,J＝7.9Hz,2H),7.56(t,J＝7.8Hz,1H),7.37(ddd,J＝27.9,16.9,8.8Hz,6H),7.27–7.21(m,3H),6.30(s,1H),6.03(s,1H).13C NMR(101MHz,CDCl3)δ163.1,161.0,152.7,143.8,139.5,132.5,129.9,129.3,128.7,128.4,126.1(J＝7.41Hz),125.4,124.1,123.2,122.7,116.6,115.7,107.0,47.2。
Example 20
The preparation method of 3- (bis (4-chlorphenyl) methyl) -4-hydroxy-2H-pyran-2-ketone comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4, 4-dichlorobenzhydrol (0.6mmol,151.9mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 12h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3- (bis (4-chlorophenyl) methyl) -4-hydroxy-2H-pyran-2-one, 123.3mg, 62% yield.
1H NMR(600MHz,CDCl3)δ7.73(dd,J＝7.9,1.1Hz,1H),7.58–7.52(m,1H),7.40(t,J＝7.4Hz,2H),7.34(dt,J＝16.5,5.9Hz,4H),7.26–7.19(m,4H),6.21(s,1H),5.94(s,1H).13C NMR(151MHz,CDCl3)δ163.1,160.7,152.7,139.80,138.2,133.6,132.3,130.2,129.8,129.5,128.7,128.2,124.0,123.2,116.5,115.8,107.4,46.8。
Example 21
The preparation of 3- ([1,1' -biphenyl ] -4-yl (phenyl) methyl) -4-hydroxy-2H-pyran-2-one is as follows:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-phenylbenzaldehyde (0.6mmol,156.2mg) as well as [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3- ([1,1' -biphenyl ] -4-yl (phenyl) methyl) -4-hydroxy-2H-pyran-2-one, 164.0mg, 81% yield.
1H NMR(400MHz,CDCl3)δ7.75(d,J＝7.9Hz,1H),7.66–7.51(m,5H),7.47–7.25(m,12H),6.35(s,1H),6.02(s,1H).13C NMR(101MHz,CDCl3)δ163.2,160.7,152.7,140.7,140.3,140.0,138.8,132.2,129.5,129.2,128.8,128.8,128.1,127.9,127.5,127.0,124.0,123.2,116.5,115.9,107.7,47.0。
Example 22
(E) The preparation method of (E) -3- (1, 3-diphenyl allyl) -4-hydroxy-2H-pyran-2-ketone comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and (E) -1, 3-diphenylprop-2-en-1-ol (0.6mmol,126.2mg) as well as [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: (E) -3- (1, 3-diphenylallyl) -4-hydroxy-2H-pyran-2-one, 161.2mg, in 90% yield.
1H NMR(600MHz,CDCl3)δ7.78(d,J＝7.9Hz,1H),7.55(t,J＝7.2Hz,1H),7.41(dd,J＝17.2,9.0Hz,6H),7.36–7.31(m,4H),7.29(d,J＝8.0Hz,2H),6.85(s,1H),6.74(dd,J＝16.1,6.1Hz,1H),6.52(d,J＝16.0Hz,1H),5.48(d,J＝5.9Hz,1H).13C NMR(151MHz,CDCl3)δ163.1,162.4,160.9,152.8,139.4,136.0,134.1,132.2,129.5,128.7,128.2,128.1,127.9,126.6,124.0,123.1,116.5,115.9,106.3,44.0。
Example 23
The preparation method of 3- (1, 3-diphenylprop-2-alkyne-1-yl) -4-hydroxy-2H-pyran-2-one comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 1, 3-diphenyl-2-yn-1-ol (0.6mmol,125.0mg) and [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 3- (1, 3-Diphenylprop-2-yn-1-yl) -4-hydroxy-2H-pyran-2-one, 136.0mg, 77% yield.
1H NMR(600MHz,CDCl3)δ7.74(d,J＝7.9Hz,1H),7.53(t,J＝7.1Hz,1H),7.33(d,J＝8.3Hz,1H),7.27(d,J＝9.0Hz,10H),6.89(d,J＝8.6Hz,2H),6.26(s,1H).13C NMR(151MHz,CDCl3)δ162.6,161.2,152.7,138.5,132.4,131.9,129.2,129.0,128.6,127.8,127.1,124.1,123.5,121.4,116.5,116.0,105.0,87.9,86.5,33.4。
Example 24
The preparation method of 4-hydroxy-3- (1-phenethyl) -2H-pyran-2-ketone comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and α -phenylethyl alcohol (0.6mmol,73.3mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 8h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (1-phenylethyl) -2H-pyran-2-one, 90.7mg, 68% yield.
1H NMR(400MHz,CDCl3)δ7.66(d,J＝7.8Hz,1H),7.48(dt,J＝14.9,7.2Hz,4H),7.34(dd,J＝19.9,7.7Hz,2H),7.23(dd,J＝15.0,7.5Hz,1H),6.10(s,1H),4.74(q,J＝7.0Hz,1H),1.67(d,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ163.5,159.7,152.5,141.5,131.9,129.8,127.9,127.3,123.9,122.9,116.4,116.1,110.1,34.5,16.5。
Example 25
The preparation method of 4-hydroxy-3- (4-methoxybenzyl) -2H-pyran-2-one comprises the following steps:
4-Hydroxycoumarin (0.5mmol,81.1mg) and 4-methoxybenzyl alcohol (0.6mmol,82.9mg) as well as [ BspD ] [ OTf ] (10 mol%, 18.2mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 80 ℃ and reacted for 24h with magnetic stirring. After the reaction is finished, column chromatography separation (adopting silica gel column; eluent: petroleum ether) is carried out to obtain a pure product: 4-hydroxy-3- (4-methoxybenzyl) -2H-pyran-2-one, 96.1mg, 67% yield.
1H NMR(400MHz,CDCl3)δ7.76(d,J＝7.9Hz,1H),7.53(t,J＝7.7Hz,1H),7.30(dd,J＝19.2,8.7Hz,4H),6.87(d,J＝8.3Hz,2H),6.52(s,1H),3.98(s,2H),3.78(s,3H).13C NMR(101MHz,CDCl3)δ163.9,160.4,158.9,152.5,131.9,129.6,129.0,124.0,122.8,116.6,115.7,114.8,104.5,55.3,29.3。
Example 26
The preparation of 4-hydroxy-7-methyl-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-hydroxy-7-methylcoumarin (0.5mmol,88.1mg) and 4-methylbenzhydryl alcohol (0.6mmol,119.0mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction, column chromatography was performed (silica gel column; eluent: petroleum ether) to give pure 4-hydroxy-7-methyl-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one (171.1 mg, 96% yield).
1H NMR(400MHz,CDCl3)δ7.59(d,J＝8.1Hz,1H),7.44–7.22(m,5H),7.19–7.03(m,6H),6.30(s,1H),5.92(s,1H),2.43(s,3H),2.34(s,3H).13C NMR(101MHz,CDCl3)δ163.5,161.0,152.9,143.3,140.2,137.6,137.2,130.2,129.3,128.8,128.7,127.6,125.2,122.9,116.6,113.5,106.9,47.0,21.8,21.1。
Example 27
The preparation of 4-hydroxy-7-methoxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-hydroxy-7-methoxycoumarin (0.5mmol,96.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) as well as [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction, column chromatography was performed (silica gel column; eluent: petroleum ether) to give 4-hydroxy-7-methoxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one (184.5 mg, 99% yield) as a pure product.
1H NMR(400MHz,CDCl3)δ7.51(s,1H),7.40–7.26(m,6H),7.18(dt,J＝24.8,8.3Hz,5H),6.26(s,1H),5.93(s,1H),2.36(d,J＝9.5Hz,6H).13C NMR(101MHz,CDCl3)δ163.4,160.7,150.9,140.1,137.7,137.0,133.6,133.1,130.2,129.3,128.8,128.6,127.7,122.8,116.2,115.6,107.8,47.0,21.1,20.9。
Example 28
The preparation of 4-hydroxy-6-methyl-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one is as follows:
4-hydroxy-6-methylcoumarin (0.5mmol,88.1mg) and 4-methylbenzhydryl alcohol (0.6mmol,119.0mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 2h with magnetic stirring. After the reaction, column chromatography was performed (silica gel column; eluent: petroleum ether) to give pure 4-hydroxy-6-methyl-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 172.7mg, in 97% yield.
1H NMR(400MHz,CDCl3)δ7.61(d,J＝8.6Hz,1H),7.42–7.23(m,5H),7.16(q,J＝8.0Hz,4H),6.81(d,J＝10.6Hz,2H),6.25(s,1H),5.90(s,1H),3.86(s,3H),2.35(s,3H).13C NMR(101MHz,CDCl3)δ163.7,163.0,161.1,154.5,140.3,137.6,137.2,130.2,129.3,128.8,128.6,127.6,124.2,112.2,109.1,105.2,100.2,55.8,46.9,21.1。
Example 29
The 6-fluoro-4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one was prepared as follows:
6-fluoro-4-hydroxycoumarin (0.5mmol,90.1mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 12h with magnetic stirring. After the reaction, column chromatography was performed (silica gel column; eluent: petroleum ether) to give 113.7mg of pure 6-fluoro-4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one in 63% yield.
1H NMR(400MHz,CDCl3)δ7.42–7.34(m,3H),7.34–7.21(m,5H),7.21–7.11(m,4H),6.40(s,1H),5.91(s,1H),2.35(s,3H).13C NMR(101MHz,CDCl3)δ162.9,159.8(t,J＝2.5Hz),157.5,148.8(d,J＝1.5Hz),139.8,137.8,136.7,130.3,129.4,128.0(d,J＝10.9Hz),127.8,119.6,119.5,118.0(d,J＝8.1),117.0(d,J＝8.8),109.1,108.7(d,J＝18.2Hz),47.1,21.1。
Example 30
The 6-chloro-4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one was prepared as follows:
6-chloro-4-hydroxycoumarin (0.5mmol,98.3mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) as well as [ BspD ] [ OTf ] (5 mol%, 9.1mg),2.0mL dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 12h with magnetic stirring. After the reaction, column chromatography was performed (silica gel column; eluent: petroleum ether) to obtain pure 6-chloro-4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one, 173.5mg, in 92% yield.
1H NMR(400MHz,CDCl3)δ7.70(s,1H),7.47(d,J＝8.7Hz,1H),7.36(dt,J＝22.4,7.2Hz,3H),7.26(s,3H),7.16(dd,J＝25.7,7.8Hz,4H),6.31(s,1H),5.90(s,1H),2.36(s,3H).13C NMR(101MHz,CDCl3)δ162.7,159.5,151.0,139.7,137.9,136.6,132.0,130.3,129.5,128.7,128.6,127.9,122.8,117.9,117.2,108.7,47.1,21.1。
Example 31
The 6-bromo-4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one was prepared as follows:
6-bromo-4-hydroxycoumarin (0.5mmol,120.5mg) and 4-methylbenzyl alcohol (0.6mmol,119.0mg) and [ BsPd ] [ OTf ] (5 mol%, 9.1mg),2.0mL of dimethyl carbonate were placed in a dry reaction flask at 60 ℃ and reacted for 12h with magnetic stirring. After the reaction, column chromatography was performed (silica gel column; eluent: petroleum ether) to give pure 6-bromo-4-hydroxy-3- (phenyl (p-tolyl) methyl) -2H-pyran-2-one (194.0 mg, 63% yield).
1H NMR(400MHz,CDCl3)δ7.85(s,1H),7.61(d,J＝8.8Hz,1H),7.43–7.30(m,3H),7.26–7.25(m,2H),7.20(d,J＝8.8Hz,3H),7.13(d,J＝7.6Hz,2H),6.31(s,1H),5.90(s,1H),2.36(s,3H).13C NMR(101MHz,CDCl3)δ162.6,159.4,151.5,139.7,137.9,136.6,134.8,130.3,129.5,128.7,128.6,127.9,125.9,118.2,117.6,116.7,108.7,47.1,21.1.HRMS-ESI:Calcd.For C23H17BrO3:420.0361,Found[M+H]+:421.0433。
As can be seen from the above embodiments, the present invention has the following features compared with the conventional methods: the catalyst is acid-functionalized ionic liquid, is metal-free and environment-friendly; the catalyst has high catalytic activity and small using amount; the operation is simple, and the corrosion of the catalyst is low; the reaction condition is mild, and the application range of the substrate is wide; the product has good selectivity and strong controllability; the reactants, the products and the catalyst are easy to separate, and the catalyst can be recycled.
It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, elements defined by the phrase "comprising.
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
1. A catalyst, characterized in that the catalyst has the following structural formula:
X-selected from any one of bisulfate, p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate.
2. The use of the catalyst of claim 1 in the synthesis of 4-hydroxycoumarin derivatives.
The synthesis method of the 4-hydroxycoumarin derivative is characterized by comprising the following steps: acid-functionalized ionic liquid is used as a catalyst to catalyze reactants to carry out alkylation reaction, so that a series of 4-hydroxycoumarin derivatives are synthesized; the reactants comprise a first reactant and a second reactant; the first reactant is a 4-hydroxycoumarin compound; the second reactant is any one of diphenyl alcohols, allyl alcohols, propargyl alcohols and benzyl alcohols;
wherein, the structural formula of the catalyst is as follows:
wherein, X-Selected from any one of bisulfate, p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate.
4. The method for synthesizing a 4-hydroxycoumarin derivative according to claim 3, wherein the 4-hydroxycoumarin compound is any one selected from 4-hydroxycoumarin, 4-hydroxy-7-methylcoumarin, 4-hydroxy-7-methoxycoumarin, 4-hydroxy-6-methylcoumarin, 6-fluoro-4-hydroxycoumarin, 6-chloro-4-hydroxycoumarin, and 6-bromo-4-hydroxycoumarin.
5. The method for synthesizing 4-hydroxycoumarin derivatives according to claim 3, wherein the diphenyl alcohol is selected from any one of benzhydrol, 4-methylbenzyl alcohol, 2-methylbenzyl alcohol, 4-methoxybenzyl alcohol, 4-dimethoxybenzhydrol, 4-fluorobenzyl alcohol, 4-chlorobenzyl alcohol, 4-bromobenzyl alcohol, 4-trifluoromethylbenzhydrol, 4-dichlorobenzhydrol, and 4-phenylbenzyl alcohol.
6. The method for synthesizing 4-hydroxycoumarin derivatives according to claim 3, wherein the allylic alcohols are (E) -1, 3-diphenyl-2-en-1-ol;
preferably, the propargyl alcohol is 1, 3-diphenyl-2-yn-1-ol;
preferably, the benzyl alcohol is selected from any one of alpha-phenylethyl alcohol and 4-methoxybenzyl alcohol.
7. The method for synthesizing 4-hydroxycoumarin derivatives according to claim 3, wherein the solvent for the alkylation reaction is dimethyl carbonate.
8. The method for synthesizing the 4-hydroxycoumarin derivative according to claim 3, wherein the reaction temperature of the alkylation reaction is 25-100 ℃ and the reaction time is 2-24 hours.
9. The method for synthesizing the 4-hydroxycoumarin derivative according to claim 3, wherein the amount of the catalyst is 1-50 mol% of the first reactant; preferably, the amount of the catalyst is 2-45 mol% of the first reactant; preferably, the amount of the catalyst accounts for 3-40 mol% of the first reactant; preferably, the amount of the catalyst accounts for 3-30 mol% of the first reactant; preferably, the amount of the catalyst accounts for 3-25 mol% of the first reactant; preferably, the catalyst is used in an amount of 3 to 15 mol% based on the first reactant.
10. The method for synthesizing the 4-hydroxycoumarin derivative according to claim 3, wherein the molar ratio of the first reactant to the second reactant is 1: 1-5; the preferred molar ratio of the first reactant to the second reactant is 1: 1.2.
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