CN110204474A - A method of synthesis replaces NH- azoles to four - Google Patents
A method of synthesis replaces NH- azoles to four Download PDFInfo
- Publication number
- CN110204474A CN110204474A CN201910504444.1A CN201910504444A CN110204474A CN 110204474 A CN110204474 A CN 110204474A CN 201910504444 A CN201910504444 A CN 201910504444A CN 110204474 A CN110204474 A CN 110204474A
- Authority
- CN
- China
- Prior art keywords
- formula
- azoles
- reaction
- synthesis
- replaces
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of methods that synthesis replaces NH- azoles to four, process are as follows: under copper catalyst and alkali existence condition, iminodiacetic acid (salt) acid esters compound shown in unsaturated ketone compound shown in formula (1) and formula (2) undergoes oxidation-[3+2] cycloaddition-aromatisation tandem reaction in a solvent, obtains shown in formula (3)NHAzoles, reaction equation are as follows:In formula (1) and formula (3), substituent R1And R2It is each independently selected from H, C1~C10 alkyl or aryl；In formula (2) and formula (3), substituent R3For C1~C10 alkyl, C1 ~ C8 ester group, aryl or benzyl；Substituent R4For C1~C10 alkyl or aryl.The present invention has many advantages, such as that raw material is cheap and easy to get, reaction step is few and post-processing is simple, in the presence of copper catalyst and alkali, reaction can be gone on smoothly under air conditions, is not necessarily to other additives and oxidant, and high income, the applicability of reaction substrate of target product are good.
Description
Technical field
The present invention relates to a kind of methods that synthesis replaces NH- azoles to four.
Background technique
Azoles are one of most important nuclear structures in nitrogenous five-ring heterocycles, widely exist in natural products
In drug.Since being reported for the first time, azole compounds begin to especially be cured by the favor of multiple fields scientist
The scientist of medicine, pesticide and Material Field.While more and more azole compounds are found, scientist is also to pyrroles's chemical combination
Object has carried out deeper research and has constructed many azole compounds with functionalization.Further, since having medical, agriculture
With with production etc. application values natural azole compounds limited amount and the excessively high factor of procurement cost so that not being able to satisfy people
Demand, so that having promoted organic chemist to be continually striving to develop effective synthetic strategy removes building pyroles chemical combination
Object.
Polysubstituted NH- pyrroles and its derivative are a kind of important nitrogenous five member ring heterocyclic compounds, with every field pair
The concern and research of azoles find that polysubstituted NH- pyrroles also widely exists in numerous natural products and embodies
Important bioactivity out.It is anti-swollen that the Ningalins A such as separated from the ascidian of Western Australia, which has cytotoxicity,
The precursor of tumor agent；Methoxati and Lycogarubins C as bacterial coenzyme is played in anti-HSV-I virus activity to focus on
It acts on.In addition, polysubstituted NH- pyrroles also has the important biomolecules such as anticancer, antibacterium, anti-pest active.At present by honest and clean
The starting material and catalyst that valence is easy to get synthesis four under conditions of simple mild replace the report of NH- azoles opposite
It is less.
In addition, tandem reaction, is called and does Domino reaction, successive reaction or tandem reaction etc..It refers to same anti-
Answer in system, reactant can continuously carry out two steps or more than reaction step synthesize corresponding object.Such reaction tool
There are many advantages of reaction, and the reaction intermediate that such as reaction generates does not need to separate, and reaction in-situ are directly used in, to solve
The separation difficult problems of some unstable intermediates；Reduce some unnecessary operations；It can be from simple starting material
Synthesize complicated organic molecule；With certain reaction selectivity etc..Tandem reaction is constantly subjected to Synthetic Organic Chemistry in recent years
The favor of family is simultaneously widely used in organic synthesis.Therefore, a kind of simple, efficient copper catalysis oxidation building is developed
Four substitution NH- azoles synthetic strategy be very it is necessary to.
Summary of the invention
It is an object of the invention to develop simple, efficient, the economic and environment-friendly synthesis of one kind to replace NH- pyroles to four
The method for closing object.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: in copper catalyst and alkali
Under existence condition, unsaturated ketone compound shown in formula (1) is with iminodiacetic acid (salt) acid esters compound shown in formula (2) molten
Oxidation-[3+2] cycloaddition-aromatisation tandem reaction is undergone in agent, after reaction, reaction solution is post-treated to obtain formula (3) institute
The NH- azoles shown, reaction equation are as follows:
In formula (1) and formula (3), substituent R1And R2It is each independently selected from H, C1~C10 alkyl or aryl；Formula (2) and formula
(3) in, substituent R3For C1~C10 alkyl, C1~C8 ester group, aryl or benzyl；Substituent R4For C1~C10 alkyl or aryl.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: the copper catalyst is
Copper acetate, copper nitrate, copper sulphate, cupric tartrate, copper chloride, copper bromide, cuprous iodide, stannous chloride, cuprous bromide, copper oxide
Or copper fluoride, preferably copper acetate；The mole of the copper catalyst is mole of unsaturated ketone compound shown in formula (1)
The 10%~200% of amount, preferably 100%.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: the alkali is inorganic base
Or organic base, the inorganic base are potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, cesium carbonate, sodium tert-butoxide, sodium bicarbonate
Or lithium hydroxide；The organic base be triethylamine, diethylamine, pyridine, piperidines, triethylene diamine or tetramethylethylenediamine, preferably
For triethylamine.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: the mole of the alkali
It is the 10%~200% of the mole of unsaturated ketone compound shown in formula (1), preferably 100%.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: the solvent is first
Benzene, dimethylbenzene, acetonitrile, 1,4- dioxane, dimethyl sulfoxide, N,N-dimethylformamide, N, N- diethylformamide, tetrahydro
Furans or 1,2- methylene chloride, preferably n,N-Dimethylformamide.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: reaction temperature is 30 DEG C
~120 DEG C, preferably 100 DEG C.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: the reaction time is
1~15h, preferably 8h.
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: shown in formula (1) not
The molar ratio of iminodiacetic acid (salt) acid esters compound shown in saturated ketone compounds and formula (2) is 1:1~3, preferably
1:2。
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that reaction solution is post-treated
The step of are as follows: saturated sodium-chloride water solution is added in reaction solution and is extracted with ethyl acetate, merges organic layer, passes through anhydrous sulphur
After sour sodium is dry, revolving removes solvent, finally carries out column chromatography for separation and obtains NH- azoles shown in the formula (3).
The method that a kind of synthesis replaces NH- azoles to four, it is characterised in that: carry out column chromatography for separation
Eluant, eluent used is the mixed liquor of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether and ethyl acetate is 1~4:1, excellent
It is selected as 2:1.
The invention has the advantages that business can get iminodiacetic acid (salt) acid esters, easily prepare beta-unsaturated ketone in one pot reaction body
In system, replace NH- azoles by synthesizing four under the catalysis oxidation of the copper catalysts such as cheap, efficient copper acetate.
This reaction can be gone on smoothly under air conditions using copper acetate as catalyst and triethylamine as alkali, be added without other
Add object and oxidant；High income, the applicability of substrate of object are good, and various substituent groups can construct corresponding four well
Replace NH- azoles.In addition, also having many advantages, such as that raw material is cheap and easy to get, reaction step is few and post-processing is simple.To close
Environmentally protective, economical and efficient a new strategy is opened at the active four substitutions NH- azoles of potential source biomolecule.
Specific embodiment
The present invention is further explained in the light of specific embodiments, but the scope of protection of the present invention is not limited thereto.
Embodiment 1
Chalcone (0.0520g, 0.25mmol), diethyl iminodiacetate are added in 25mL reaction tube
(0.0945g,0.5mmol)、Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol), then 100
DEG C DMF (1.0mL) in react 8h.After reaction by TLC detection, with 10mL saturated sodium-chloride water solution and ethyl acetate
(3 × 10mL) extraction merges organic layer by removing solvent with Rotary Evaporators, most after anhydrous sodium sulfate drying
Column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1) is carried out afterwards, obtains 90% yield
Target compound, the compound are white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.13 (s, 1H), 7.79 (d, J=7.5Hz, 2H), 7.49 (t, J
=7.5Hz, 1H), 7.36 (t, J=8.0Hz, 2H), 7.30-7.29 (m, 2H), 7.22-7.20 (m, 3H), 4.25 (q, J=
7.0Hz, 2H), 4.09 (q, J=7.0Hz, 2H), 1.18 (t, J=7.5Hz, 3H), 0.91 (t, J=7.0Hz, 3H)；13C NMR
(125MHz,CDCl3)δ192.40,159.80,159.27,137.91,132.82,131.68,130.90,129.80(2C),
129.07(2C),128.51,128.00(2C),127.33,127.22(2C),122.41,121.78,61.13,60.89,
13.64,13.19；HRMS(ESI)m/z calcd for C23Н21NO5 +[M+H]+392.1492,found 392.1494。
Embodiment 2
In 25mL reaction tube be added (E) -1- (4- bromophenyl) -3- phenyl propyl- 2- alkene -1- ketone (0.0718g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0253g, 0.25mmol) and Cu (NO3)2
(0.0468g, 0.25mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).After reaction by TLC detection, it uses
10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL) are extracted, and organic layer is merged and passes through anhydrous sodium sulfate
After drying, with Rotary Evaporators remove solvent, finally carry out column chromatography for separation (eluant, eluent be volume ratio be 2:1 petroleum ether with
Ethyl acetate mixtures), the target compound of 81% yield is obtained, which is yellow solid.
Characterize data:1H NMR(500MHz,CDCl3)δ9.96(s,1H),7.58–7.55(m,2H),7.44–7.42(m,
2H), 7.20 (d, J=2.0Hz, 1H), 7.18 (d, J=3.0Hz, 1H), 7.17-7.15 (m, 3H), 4.18 (q, J=7.0Hz,
2H), 4.06 (q, J=7.5Hz, 2H), 1.12 (t, J=7.0Hz, 3H), 0.93 (t, J=7.0Hz, 3H)13C NMR
(125MHz,CDCl3)δ191.67,159.99,159.36,136.90,131.78,131.69(2C),131.14,130.82
(2C),130.04(2C),128.45,128.35,127.82,127.65(2C),122.61,122.09,61.60,61.29,
13.96,13.67.HRMS(ESI)m/z calcd for C23H21BrNO5 +(M+H)+470.05976,found 470.05942。
Embodiment 3
In 25mL reaction tube be added (E) -1- (4- nitrobenzophenone) -3- phenyl propyl- 2- alkene -1- ketone (0.0575g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0253g, 0.25mmol) and CuCl
(0.0250g, 0.25mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).After reaction by TLC detection, it uses
10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL) are extracted, and organic layer is merged and passes through anhydrous sodium sulfate
After drying, with Rotary Evaporators remove solvent, finally carry out column chromatography for separation (eluant, eluent be volume ratio be 2:1 petroleum ether with
Ethyl acetate mixtures), the target compound of 88% yield is obtained, which is red solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.05 (s, 1H), 8.11 (d, J=8.5Hz, 2H), 7.83 (d, J
=9.0Hz, 2H), 7.17-7.15 (m, 2H), 7.15-7.12 (m, 3H), 4.19 (d, J=7.0Hz, 2H), 4.07 (q, J=
7.0Hz, 2H), 1.10 (t, J=7.0Hz, 3H), 0.95 (t, J=7.5Hz, 3H)13C NMR(125MHz,CDCl3)δ
190.93,159.90,159.08,150.20,142.38,131.55,131.22,130.15(2C),130.02(2C),
127.96,127.78,127.71(2C),123.56(2C),122.87,122.28,61.74,61.40,13.92,
13.76.HRMS(ESI)m/z calcd for C23H21N2O7 +(M+H)+437.13433,found 437.13440。
Embodiment 4
In 25mL reaction tube be added (E) -3- (4- methoxyphenyl) -1- phenyl propyl- 2- alkene -1- ketone (0.0595g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0253g, 0.25mmol) and Cu (OAc)2
(0.0050g, 0.025mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).After reaction by TLC detection, it uses
10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL) are extracted, and organic layer is merged and passes through anhydrous sodium sulfate
After drying, with Rotary Evaporators remove solvent, finally carry out column chromatography for separation (eluant, eluent be volume ratio be 2:1 petroleum ether with
Ethyl acetate mixtures), the target compound of 92% yield is obtained, which is white solid.
Characterize data:1H NMR 1H NMR(500MHz,CDCl3) δ 10.13 (s, 1H), 7.75 (d, J=8.5Hz, 2H),
7.30-7.29 (m, 2H), 7.21-7.20 (m, 3H), 6.83 (d, J=8.0Hz, 2H), 4.24 (q, J=6.5Hz, 2H), 4.12
(q, J=7.0Hz, 2H), 3.81 (s, 3H), 1.17 (t, J=7.0Hz, 3H), 0.97 (t, J=7.0Hz, 3H)13C NMR
(125MHz,CDCl3)δ191.35,163.63,160.17,159.65,132.12,131.74(2C),131.43,130.96,
130.09(2C),129.24,127.60,127.52(2C),122.49,121.99,113.56(2C),61.39,61.17,
55.43,13.96,13.65.HRMS(ESI)m/z calcd for C24H23NO6 +(M+H)+422.1598,found
422.1604。
Embodiment 5
In 25mL reaction tube be added (E) -3- (4- nitrobenzophenone) -1- phenyl propyl- 2- alkene -1- ketone (0.0575g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0253g, 0.25mmol) and Cu (OAc)2
(0.0996g, 0.50mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).After reaction by TLC detection, it uses
10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL) are extracted, and organic layer is merged and passes through anhydrous sodium sulfate
After drying, with Rotary Evaporators remove solvent, finally carry out column chromatography for separation (eluant, eluent be volume ratio be 2:1 petroleum ether with
Ethyl acetate mixtures), the target compound of 94% yield is obtained, which is yellow solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.47 (s, 1H), 8.10 (d, J=8.5Hz, 2H), 7.79 (d, J
=7.5Hz, 2H), 7.55-7.49 (m, 3H), 7.40 (t, J=7.5Hz, 2H), 4.28 (q, J=7.0Hz, 2H), 4.10 (q, J
=7.0Hz, 2H), 1.20 (t, J=7.0Hz, 3H), 0.89 (t, J=7.0Hz, 3H)13C NMR(125MHz,CDCl3)δ
191.83,159.31,159.04,146.92,138.91,137.70,133.29,130.93(2C),129.01(2C),
128.40,128.26(2C),123.70,123.10,122.50(2C),122.15,61.41,61.32,13.71,
13.12.HRMS(ESI)m/z calcd for C23H21N2O7 +(M+H)+437.13433,found 437.13480。
Embodiment 6
In 25mL reaction tube be added (E) -1- phenyl -3- (tolyl) propyl- 2- alkene -1- ketone (0.0555g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Na2CO3(0.0265g, 0.25mmol) and Cu
(OAc)2(0.0498g, 0.25mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).Terminated by TLC detection reaction
Afterwards, it is extracted with 10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL), organic layer is merged through anhydrous sulphur
After sour sodium is dry, solvent is removed with Rotary Evaporators, finally carrying out column chromatography for separation, (eluant, eluent is the petroleum that volume ratio is 2:1
Ether and ethyl acetate mixtures), the target compound of 70% yield is obtained, which is white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.02 (s, 1H), 7.78 (d, J=7.5Hz, 2H), 7.49 (t, J
=7.5Hz, 1H), 7.36 (t, J=7.5Hz, 2H), 7.12-7.05 (m, 3H), 7.01 (d, J=7.0Hz, 1H), 4.25 (q, J
=7.5Hz, 2H), 4.09 (q, J=7.5Hz, 2H), 2.24 (s, 3H), 1.19 (t, J=7.0Hz, 3H), 0.92 (t, J=
7.5Hz,3H).13C NMR(125MHz,CDCl3)δ192.46,159.84,159.29,138.00,136.59,132.79,
131.50,131.06,130.63,129.09(2C),128.54,128.14,127.99(2C),127.15,126.82,
122.35,121.73,61.13,60.85,21.01,13.67,13.23.HRMS(ESI)m/z calcd for C24H24NO5 +(M
+H)+406.16490,found 406.16461。
Embodiment 7
In 25mL reaction tube be added (E) -1- phenyl -3- (p-methylphenyl) propyl- 2- alkene -1- ketone (0.0555g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), triethylene diamine (0.0251g, 0.25mmol) and
Cu(OAc)2(0.0498g, 0.25mmol) then reacts 8h in 80 DEG C of DMF (1.0mL).Terminated by TLC detection reaction
Afterwards, it is extracted with 10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL), organic layer is merged through anhydrous sulphur
After sour sodium is dry, solvent is removed with Rotary Evaporators, finally carrying out column chromatography for separation, (eluant, eluent is the petroleum that volume ratio is 2:1
Ether and ethyl acetate mixtures), the target compound of 90% yield is obtained, which is white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.01 (s, 1H), 7.71 (d, J=7.5Hz, 2H), 7.41 (t, J
=7.0Hz, 1H), 7.28 (t, J=8.0Hz, 2H), 7.11 (d, J=8.0Hz, 2H), 6.95 (d, J=8.0Hz, 2H), 4.19
(q, J=7.0Hz, 2H), 4.00 (q, J=7.0Hz, 2H), 2.18 (s, 3H), 1.14 (t, J=7.5Hz, 3H), 0.82 (t, J=
7.0Hz,3H).13C NMR(125MHz,CDCl3)δ192.87,160.06,159.62,138.30,137.33,133.10,
131.41,129.94(2C),129.41(2C),128.91,128.82,128.33(2C),128.32(2C),122.61,
122.01,61.40,61.16,21.21,14.05,13.49.HRMS(ESI)m/z calcd for C24H24NO5 +(M+H)+
406.16490,found406.16531。
Embodiment 8
In 25mL reaction tube be added (E) -1- phenyl -3- (o-tolyl) propyl- 2- alkene -1- ketone (0.0555g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0025g, 0.025mmol) and Cu
(OAc)2(0.0498g, 0.25mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).Terminated by TLC detection reaction
Afterwards, it is extracted with 10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL), organic layer is merged through anhydrous sulphur
After sour sodium is dry, solvent is removed with Rotary Evaporators, finally carrying out column chromatography for separation, (eluant, eluent is the petroleum that volume ratio is 2:1
Ether and ethyl acetate mixtures), the target compound of 74% yield is obtained, which is white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.23 (s, 1H), 7.77 (d, J=7.5Hz, 2H), 7.48 (t, J
=7.0Hz, 1H), 7.36 (t, J=8.0Hz, 2H), 7.13-7.09 (m, 2H), 7.06-7.00 (m, 2H), 4.30-4.11 (m,
2H), 4.10-4.03 (m, 2H), 2.16 (s, 3H), 1.05 (t, J=7.0Hz, 3H), 0.87 (t, J=7.0Hz, 3H)13C NMR
(125MHz,CDCl3)δ192.30,160.14,159.70,138.29,137.16,133.01,132.06,130.64,
130.00,129.28(3C),128.75,128.22(2C),127.84,124.90,123.00,122.94,61.41,61.02,
20.21,13.76,13.45.HRMS(ESI)m/z calcd for C24H24NO5 +(M+H)+406.16490,found
406.16544。
Embodiment 9
In 25mL reaction tube be added (E) -3- (2,4 dichloro benzene base) -1- phenyl propyl- 2- alkene -1- ketone (0.0690g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0506g, 0.50mmol) and Cu (OAc)2
(0.0498g, 0.25mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).After reaction by TLC detection, it uses
10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL) are extracted, and organic layer is merged and passes through anhydrous sodium sulfate
After drying, with Rotary Evaporators remove solvent, finally carry out column chromatography for separation (eluant, eluent be volume ratio be 2:1 petroleum ether with
Ethyl acetate mixtures), the target compound of 70% yield is obtained, which is yellow solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.34 (s, 1H), 7.80-7.77 (m, 2H), 7.50 (t, J=
7.0Hz, 1H), 7.37 (t, J=8.0Hz, 2H), 7.32 (d, J=2.0Hz, 1H), 7.22-7.22 (m, 1H), 7.17-7.15
(m, 1H), 4.30-4.24 (m, 1H), 4.20-4.15 (m, 1H), 4.06 (q, J=7.0Hz, 2H), 1.13 (t, J=7.5Hz,
3H), 0.88 (t, J=7.5Hz, 3H)13C NMR(125MHz,CDCl3)δ191.86,159.73,159.47,138.04,
135.06,134.34,133.20,132.79,130.33,129.37(2C),128.77,128.63,128.28(2C),
126.54,126.49,123.55,123.28,61.53,61.34,13.79,13.42.HRMS(ESI)m/z calcd for
C23H20Cl2NO5 +(M+H)+460.07130,found 460.07172。
Embodiment 10
In 25mL reaction tube be added (E) -3- (naphthalene -2- base) -1- phenyl propyl- 2- alkene -1- ketone (0.0645g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0253g, 0.25mmol) and Cu (OAc)2
(0.0498g, 0.25mmol) then reacts 8h in 100 DEG C of DMSO (1.0mL).After reaction by TLC detection, it uses
10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL) are extracted, and organic layer is merged and passes through anhydrous sodium sulfate
After drying, with Rotary Evaporators remove solvent, finally carry out column chromatography for separation (eluant, eluent be volume ratio be 2:1 petroleum ether with
Ethyl acetate mixtures), the target compound of 88% yield is obtained, which is white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.16 (s, 1H), 8.20 (s, 1H), 7.96 (d, J=8.0Hz,
1H), 7.85-7.81 (m, 3H), 7.56 (t, J=7.0Hz, 1H), 7.49 (t, J=7.5Hz, 1H), 7.33 (d, J=6.5Hz,
2H), 7.18-7.17 (m, 3H), 4.27 (q, J=6.5Hz, 2H), 4.05 (q, J=6.5Hz, 2H), 1.19 (t, J=7.0Hz,
3H), 0.85 (t, J=7.0Hz, 3H)13C NMR(125MHz,CDCl3)δ192.69,160.17,159.61,135.69,
135.66,132.40,132.03,131.98,131.25,130.06(2C),129.63,129.01,128.56,128.26,
127.77,127.67,127.58(2C),126.66,124.38,122.79,122.12,61.46,61.24,13.97,
13.55.HRMS(ESI)m/z calcd for C27H24NO5 +(M+H)+442.16490,found 442.16495。
Embodiment 11
In 25mL reaction tube be added (E) -1- (furans -2- base) -3- phenyl propyl- 2- alkene -1- ketone (0.0495g,
0.25mmol), diethyl iminodiacetate (0.0945g, 0.5mmol), Et3N (0.0253g, 0.25mmol) and Cu (OAc)2
(0.0498g, 0.25mmol) then reacts 8h in 100 DEG C of Toulene (1.0mL).After reaction by TLC detection,
It is extracted with 10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL), organic layer is merged and passes through anhydrous slufuric acid
After sodium is dry, solvent is removed with Rotary Evaporators, finally carrying out column chromatography for separation, (eluant, eluent is the petroleum ether that volume ratio is 2:1
With ethyl acetate mixtures), the target compound of 77% yield is obtained, which is white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.27 (s, 1H), 7.51 (d, J=1.0Hz, 1H), 7.32-
7.30 (m, 2H), 7.27-7.23 (m, 3H), 6.93 (d, J=3.0Hz, 1H), 6.43 (dd, J=3.5,2.0Hz, 1H), 4.23
(q, J=7.0Hz, 2H), 4.19 (q, J=7.5Hz, 2H), 1.16 (t, J=7.0Hz, 3H), 1.07 (t, J=7.0Hz, 3H)
.13C NMR(125MHz,CDCl3)δ179.51,160.09,159.60,153.73,146.86,131.91,131.23,130.18
(2C),127.65,127.59,127.52(2C),123.26,121.93,119.38,112.33,61.51,61.19,13.91,
13.78.HRMS(ESI)m/z calcd for C21H20NO6 +(M+H)+382.12851,found 382.12897。
Embodiment 12
Chalcone (0.0520g, 0.25mmol), iminodiacetic acid (salt) dimethyl phthalate are added in 25mL reaction tube
(0.0805g,0.5mmol)、Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol), then 30
DEG C DMF (1.0mL) in react 8h.After reaction by TLC detection, with 10mL saturated sodium-chloride water solution and ethyl acetate
(3 × 10mL) extraction merges organic layer by removing solvent with Rotary Evaporators, most after anhydrous sodium sulfate drying
Column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1) is carried out afterwards, obtains 85% yield
Target compound, the compound are yellow solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.26 (s, 1H), 7.75 (d, J=7.5Hz, 2H), 7.46 (t, J
=7.0Hz, 1H), 7.33 (t, J=7.5Hz, 2H), 7.29-7.27 (m, 2H), 7.20-7.19 (m, 3H), 3.77 (s, 3H),
3.63(s,3H).13C NMR(125MHz,CDCl3)δ192.34,160.07,159.50,137.48,132.76,131.42,
130.80,129.58(2C),128.88(2C),128.74,127.88(2C),127.29,127.21(2C),122.20,
121.25,51.75,51.59.HRMS(ESI)m/z calcd for C21H18NO5 +(M+H)+364.11795,found
364.11780。
Embodiment 13
Chalcone (0.0520g, 0.25mmol), iminodiacetic acid dipropyl are added in 25mL reaction tube
(0.0109g,0.5mmol)、Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol), then 120
DEG C DMF (1.0mL) in react 8h.After reaction by TLC detection, with 10mL saturated sodium-chloride water solution and ethyl acetate
(3 × 10mL) extraction merges organic layer by removing solvent with Rotary Evaporators, most after anhydrous sodium sulfate drying
Column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1) is carried out afterwards, obtains 90% yield
Target compound, the compound are white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.15 (s, 1H), 7.81 (dd, J=8.5,1.0Hz, 2H),
7.52-7.48 (m, 1H), 7.37 (t, J=8.0Hz, 2H), 7.30-7.28 (m, 1H), 7.23-7.20 (m, 3H), 5.17-5.10
(m, 1H), 5.00-4.95 (m, 1H), 1.16 (d, J=6.0Hz, 6H), 0.90 (d, J=6.5Hz, 6H)13C NMR(125MHz,
CDCl3)δ192.70,159.72,159.22,138.49,133.10,132.19,131.10,130.16(2C),129.44
(2C),128.47,128.32(2C),127.53,127.45(2C),122.94,122.56,69.44,69.06,21.65(2C),
21.15(2C).HRMS(ESI)m/z calcd for C25H26NO5 +(M+H)+420.18055,found 420.18073。
Embodiment 14
Chalcone (0.0520g, 0.25mmol), iminodiacetic acid diisopropyl ester are added in 25mL reaction tube
(0.0109g,0.5mmol)、Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol), then 100
DEG C DMF (1.0mL) in react 1h.After reaction by TLC detection, with 10mL saturated sodium-chloride water solution and ethyl acetate
(3 × 10mL) extraction merges organic layer by removing solvent with Rotary Evaporators, most after anhydrous sodium sulfate drying
Column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1) is carried out afterwards, obtains 93% yield
Target compound, the compound are white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.19 (s, 1H), 7.79 (d, J=7.5Hz, 2H), 7.48 (t, J
=7.5Hz, 1H), 7.35 (t, J=7.5Hz, 2H), 7.23-7.18 (m, 2H), 7.29-7.27 (m, 3H), 4.15 (t, J=
6.5Hz, 2H), 4.01 (t, J=6.5Hz, 2H), 1.57-1.49 (m, 2H), 1.34-1.26 (m, 2H), 0.75 (t, J=
7.5Hz, 3H), 0.66 (t, J=7.5Hz, 3H)13C NMR(125MHz,CDCl3)δ192.74,160.45,159.80,
138.01,133.19,132.13,130.93,130.08(2C),129.42(2C),128.80,128.31(2C),127.61,
127.54(2C),122.69,122.23,67.14,66.91,21.74,21.49,10.27,10.14.HRMS(ESI)m/z
calcd for C25H26NO5 +(M+H)+420.18055,found 420.18057。
Embodiment 15
In 25mL reaction tube be added chalcone (0.0520g, 0.25mmol), n-benzylglycine ethyl ester (0.0965g,
0.5mmol)、Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol), then in 100 DEG C of DMF
15h is reacted in (1.0mL).After reaction by TLC detection, with 10mL saturated sodium-chloride water solution and ethyl acetate (3 ×
It 10mL) extracts, organic layer is merged by removing solvent with Rotary Evaporators after anhydrous sodium sulfate drying, it is most laggard
Row column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1), obtains the target of 45% yield
Compound, the compound are white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 9.63 (s, 1H), 7.65 (d, J=7.5Hz, 2H), 7.45 (d, J
=6.5Hz, 2H), 7.30-7.27 (m, 6H), 7.19-7.12 (m, 6H), 4.19 (q, J=7.0Hz, 2H), 1.14 (t, J=
7.0Hz,3H).13C NMR(125MHz,CDCl3)δ193.83,161.22,138.24,136.60,133.21,132.83,
132.51,130.55,130.40(2C),129.77(2C),128.73(2C),128.69,127.95(2C),127.86(2C),
127.24(2C),127.17,123.24,119.12,60.71,14.01.HRMS(ESI)m/z calcd for C26H22NO3 +(M
+H)+396.15942,found 396.15979。
Embodiment 16
(E)-amyl- 3- alkene -2- ketone (0.0210g, 0.25mmol), iminodiacetic acid diethyl are added in 25mL reaction tube
Ester (0.0945g, 0.5mmol), Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol), then exists
5h is reacted in 100 DEG C of DMF (1.0mL).After reaction by TLC detection, with 10mL saturated sodium-chloride water solution and acetic acid
Ethyl ester (3 × 10mL) extraction merges organic layer by being removed with Rotary Evaporators molten after anhydrous sodium sulfate drying
Agent finally carries out column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1), obtains 65% receipts
The target compound of rate, the compound are yellow liquid.
Characterize data:1H NMR(500MHz,CDCl3)δ9.72(s,1H),4.36(m,4H),2.54(s,3H),2.32
(s, 3H), 1.37 (dd, J=13.5,7.0Hz, 6H)13C NMR(125MHz,CDCl3)δ199.73,160.63,159.43,
131.11,127.03,122.36,122.01,61.67,61.09,32.18,14.35,14.16,10.69.HRMS(ESI)m/z
calcd for C13H17NO5Na+(M+Na)+290.0999,found 290.1030。
Embodiment 17
(E) -1- phenyl but-2-ene -1- ketone (0.0365g, 0.25mmol), iminodiacetic acid (salt) are added in 25mL reaction tube
Diethyl phthalate (0.0473g, 0.25mmol), Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol),
Then 8h is reacted in 100 DEG C of DMF (1.0mL).After reaction by TLC detection, with 10mL saturated sodium-chloride water solution
It is extracted with ethyl acetate (3 × 10mL), organic layer is merged by being removed after anhydrous sodium sulfate drying with Rotary Evaporators
Solvent is removed, finally column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1) is carried out, obtains
The target compound of 81% yield, the compound are white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 9.98 (s, 1H), 7.33 (t, J=5.4Hz, 3H), 7.31-7.28
(m, 2H), 4.36 (q, J=7.1Hz, 2H), 4.19 (q, J=7.1Hz, 2H), 2.21 (s, 3H), 1.35 (t, J=7.1Hz,
3H), 1.13 (t, J=7.1Hz, 3H).
Embodiment 18
In 25mL reaction tube be added (E) -3- phenyl -1- (thiophene -2- base) propyl- 2- alkene -1- ketone (0.0535g,
0.25mmol), diethyl iminodiacetate (0.1419g, 0.75mmol), Et3N (0.0253g, 0.25mmol) and Cu
(OAc)2(0.0498g, 0.25mmol) then reacts 8h in 100 DEG C of DMF (1.0mL).Terminated by TLC detection reaction
Afterwards, it is extracted with 10mL saturated sodium-chloride water solution and ethyl acetate (3 × 10mL), organic layer is merged through anhydrous sulphur
After sour sodium is dry, solvent is removed with Rotary Evaporators, finally carrying out column chromatography for separation, (eluant, eluent is the petroleum that volume ratio is 2:1
Ether and ethyl acetate mixtures), the target compound of 82% yield is obtained, which is white solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 10.20 (s, 1H), 7.59 (dd, J=5.0,1.5Hz, 1H),
7.38 (dd, J=3.5,1.0Hz, 1H), 7.35-7.32 (m, 2H), 7.26-7.22 (m, 3H), 6.99 (dd, J=4.5,
3.5Hz, 1H), 4.25 (q, J=7.0Hz, 2H), 4.17 (q, J=7.0Hz, 2H), 1.18 (t, J=7.5Hz, 3H), 1.03 (t,
J=7.0Hz, 3H)13C NMR(125MHz,CDCl3)δ184.31,159.83,159.29,145.41,134.13,134.06,
131.62,130.57,129.87(2C),128.43,127.68,127.44,127.30(2C),122.49,121.64,61.25,
60.96,13.66,13.33.HRMS(ESI)m/z calcd for C21H20NO5S+(M+H)+398.10567,found
398.10617。
Embodiment 19
Chalcone (0.0365g, 0.25mmol), diethyl iminodiacetate are added in 25mL reaction tube
(0.0945g,0.5mmol)、Et3N (0.0253g, 0.25mmol) and Cu (OAc)2(0.0498g, 0.25mmol), then 100
DEG C DMF (1.0mL) and nitrogen atmosphere under react 8h.After reaction by TLC detection, with 10mL saturated sodium-chloride water solution
It is extracted with ethyl acetate (3 × 10mL), organic layer is merged by being removed after anhydrous sodium sulfate drying with Rotary Evaporators
Solvent is removed, finally column chromatography for separation (eluant, eluent is the petroleum ether and ethyl acetate mixtures that volume ratio is 2:1) is carried out, obtains
The target compound of 43% yield, the compound are yellow solid.
Characterize data:1H NMR(500MHz,CDCl3) δ 7.83 (d, J=8.0Hz, 2H), 7.54 (t, J=7.5Hz, 1H),
7.41 (t, J=8.0Hz, 2H), 7.33-7.30 (m, 4H), 7.26-7.23 (m, 1H), 4.48 (t, J=7.0Hz, 1H), 4.43-
4.36(m,1H),4.20–4.23(m,2H),4.15–4.10(m,1H),4.03–3.97(m,2H),3.96–3.91(m,1H),
3.82 (t, J=7.0Hz, 1H), 2.93 (s, 1H), 1.17 (t, J=7.0Hz, 3H), 0.99 (t, J=7.0Hz, 3H).
Claims (10)
1. a kind of method that synthesis replaces NH- azoles to four, it is characterised in that: in copper catalyst and alkali existence condition
Under, unsaturated ketone compound shown in formula (1) is undergone in a solvent with iminodiacetic acid (salt) acid esters compound shown in formula (2)
Oxidation-[3+2] cycloaddition-aromatisation tandem reaction, after reaction, reaction solution is post-treated to be obtained shown in formula (3)NHPyrrole
Class compound is coughed up, reaction equation is as follows:
In formula (1) and formula (3), substituent R1And R2It is each independently selected from H, C1~C10 alkyl or aryl；
In formula (2) and formula (3), substituent R3For C1~C10 alkyl, C1 ~ C8 ester group, aryl or benzyl；Substituent R4For C1~
C10 alkyl or aryl.
2. the method that a kind of synthesis as described in claim 1 replaces NH- azoles to four, it is characterised in that: described
Copper catalyst is copper acetate, copper nitrate, copper sulphate, cupric tartrate, copper chloride, copper bromide, cuprous iodide, stannous chloride, bromination
Cuprous, copper oxide or copper fluoride, preferably copper acetate；The mole of the copper catalyst is unsaturated ketone shown in formula (1)
The 10%~200% of the mole of compound, preferably 100%.
3. the method that a kind of synthesis as described in claim 1 replaces NH- azoles to four, it is characterised in that: described
Alkali is inorganic base or organic base, and the inorganic base is potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, cesium carbonate, the tert-butyl alcohol
Sodium, sodium bicarbonate or lithium hydroxide；The organic base is triethylamine, diethylamine, pyridine, piperidines, triethylene diamine or tetramethyl
Ethylenediamine, preferably triethylamine.
4. the method that a kind of synthesis as claimed in claim 3 replaces NH- azoles to four, it is characterised in that: described
The mole of alkali be formula (1) shown in unsaturated ketone compound mole 10%~200%, preferably 100%.
5. the method that a kind of synthesis as described in claim 1 replaces NH- azoles to four, it is characterised in that: described
Solvent is toluene, dimethylbenzene, acetonitrile, 1,4- dioxane, dimethyl sulfoxide, N,N-dimethylformamide, N, N- diethyl first
Amide, tetrahydrofuran or 1,2- methylene chloride, preferably n,N-Dimethylformamide.
6. the method that a kind of synthesis as described in claim 1 replaces NH- azoles to four, it is characterised in that: reaction
Temperature is 30 DEG C~120 DEG C, preferably 100 DEG C.
7. the method that a kind of synthesis as described in claim 1 replaces NH- azoles to four, it is characterised in that: described
Reaction time is 1~15 h, preferably 8 h.
8. the method that a kind of synthesis as described in claim 1 replaces NH- azoles to four, it is characterised in that: formula
(1) molar ratio of iminodiacetic acid (salt) acid esters compound shown in unsaturated ketone compound shown in and formula (2) is 1:
1 ~ 3, preferably 1: 2.
9. the method that a kind of synthesis as described in claim 1 replaces NH- azoles to four, it is characterised in that reaction solution
Post-treated step are as follows: saturated sodium-chloride water solution is added in reaction solution and is extracted with ethyl acetate, merges organic layer, leads to
After crossing anhydrous sodium sulfate drying, revolving removes solvent, finally carries out column chromatography for separation and obtains shown in the formula (3)NHPyrroles
Class compound.
10. the method that a kind of synthesis as claimed in claim 9 replaces NH- azoles to four, it is characterised in that: into
Eluant, eluent used in row column chromatography for separation is the mixed liquor of petroleum ether and ethyl acetate, the volume ratio of the petroleum ether and ethyl acetate
It is 1 ~ 4: 1, preferably 2: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910504444.1A CN110204474B (en) | 2019-06-12 | 2019-06-12 | Method for synthesizing tetra-substituted NH-pyrrole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910504444.1A CN110204474B (en) | 2019-06-12 | 2019-06-12 | Method for synthesizing tetra-substituted NH-pyrrole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110204474A true CN110204474A (en) | 2019-09-06 |
| CN110204474B CN110204474B (en) | 2020-10-30 |
Family
ID=67792179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910504444.1A Active CN110204474B (en) | 2019-06-12 | 2019-06-12 | Method for synthesizing tetra-substituted NH-pyrrole compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110204474B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113801050A (en) * | 2021-09-27 | 2021-12-17 | 山东大学 | Polysubstituted beta-lactam compound and preparation method thereof |
| CN114262290A (en) * | 2021-12-20 | 2022-04-01 | 华东师范大学 | 4-methylene pyrrolidine-2-thioketone compound and synthesis method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050054857A1 (en) * | 2003-09-05 | 2005-03-10 | Pagenkopf Brian L. | Synthesis of pyrroles |
| CN104788361A (en) * | 2015-04-21 | 2015-07-22 | 杭州科巢生物科技有限公司 | Synthetic method for 5-azaspiro[2.4]heptane-6-formic acid derivative |
| CN105130871A (en) * | 2015-07-29 | 2015-12-09 | 南京农业大学 | Pyrrolidone sulfur derivatives and their preparation method and application |
| CN106565583A (en) * | 2016-11-15 | 2017-04-19 | 淮阴师范学院 | Preparation method of polysubstitued pyrrole derivative |
| CN109851544A (en) * | 2019-01-28 | 2019-06-07 | 浙江师范大学 | A kind of preparation method of polysubstituted pyrrole compound |
-
2019
- 2019-06-12 CN CN201910504444.1A patent/CN110204474B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050054857A1 (en) * | 2003-09-05 | 2005-03-10 | Pagenkopf Brian L. | Synthesis of pyrroles |
| CN104788361A (en) * | 2015-04-21 | 2015-07-22 | 杭州科巢生物科技有限公司 | Synthetic method for 5-azaspiro[2.4]heptane-6-formic acid derivative |
| CN105130871A (en) * | 2015-07-29 | 2015-12-09 | 南京农业大学 | Pyrrolidone sulfur derivatives and their preparation method and application |
| CN106565583A (en) * | 2016-11-15 | 2017-04-19 | 淮阴师范学院 | Preparation method of polysubstitued pyrrole derivative |
| CN109851544A (en) * | 2019-01-28 | 2019-06-07 | 浙江师范大学 | A kind of preparation method of polysubstituted pyrrole compound |
Non-Patent Citations (4)
| Title |
|---|
| ALEXEY V. GALENKO等: "Synthesis of 3-(1,2-dioxoethyl)- and 2,3-dicarbonyl-containing pyrroles", 《TETRAHEDRON》 * |
| HANUMAN P. KALMODE等: "Deep eutectic solvent: a simple, environmentally benign reaction media for regioselective synthesis of 2,3,4-trisubstituted 1H-pyrroles", 《RSC ADVANCES》 * |
| NINI ZHOU等: "Cu/Mn Co-oxidized Cyclization for the Synthesis of Highly Substituted Pyrrole Derivatives from Amino Acid Esters: A Strategy for the Biomimetic Syntheses of Lycogarubin C and Chromopyrrolic Acid", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| 辛明: "基于查尔酮的吡咯/二氢吡咯化合物的合成研究", 《浙江工业大学硕士学位论文》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113801050A (en) * | 2021-09-27 | 2021-12-17 | 山东大学 | Polysubstituted beta-lactam compound and preparation method thereof |
| CN113801050B (en) * | 2021-09-27 | 2023-11-14 | 山东大学 | Polysubstituted beta-lactam compound and preparation method thereof |
| CN114262290A (en) * | 2021-12-20 | 2022-04-01 | 华东师范大学 | 4-methylene pyrrolidine-2-thioketone compound and synthesis method and application thereof |
| CN114262290B (en) * | 2021-12-20 | 2024-03-22 | 华东师范大学 | 4-methylene pyrrolidine-2-thioketone compound, and synthetic method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110204474B (en) | 2020-10-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Talukdar et al. | Ring opening of DA-cyclopropanes with electron rich arene/heteroarene: synthesis of 2-(2, 2-diarylethyl) malonates | |
| CN105254589B (en) | A method of preparing heart failure drugs intermediate | |
| CN110204474A (en) | A method of synthesis replaces NH- azoles to four | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| JP2013170151A (en) | Direct method for producing indole-3-triflone and indole triflone derivative | |
| CN111925356B (en) | Synthesis method and application of chiral quinoline-imidazoline ligand | |
| JP6548214B2 (en) | Catalyst having an aminosalicylaldimine ligand coordinated to metal and method for producing iodocyclic compound using the same | |
| JP4649645B2 (en) | Process for producing optically active alcohol compounds | |
| CN106749335B (en) | A kind of preparation method and application of halogenated oxygen cephalo-type intermediate | |
| CN105348194B (en) | Fluorine-containing phenanthridine derivatives and preparation method thereof | |
| US11053265B2 (en) | Optically active substituted 2,3-bisphosphinoquinoxalines and processes for producing the same | |
| CN106146556B (en) | Er Fu Jia Ji phosphonium salts and its preparation method and application | |
| CN108059591A (en) | A kind of catalysis method of asymmetric synthesis of chiral alpha-fluoro-beta-acetenyl ketone compound | |
| CN105732648A (en) | Nitrogen heterocyclic ring compound of pyrrolofuran and synthetic method | |
| CN110028448B (en) | Preparation method of 3-hydroxy-2,3-dihydroisoquinoline-1, 4-diketone compound | |
| CN110240554B (en) | Alpha-thioether aryl acetonitrile compound and synthetic method thereof | |
| CN110372675B (en) | Selective preparation method of N-1 and N2-oxyalkyl substituted 1,2, 3-triazole compound | |
| CN109970560B (en) | Preparation method of tri-substituted 1, 3-diene compound | |
| CN105669583A (en) | High-regioselectivity and high-stereoselectivity method for synthesizing (Z)-alpha/beta-fluoroolefin amide | |
| CN105712956B (en) | A kind of preparation method of gentle efficient polyfunctional group substituted epoxy class compound | |
| CN104447439B (en) | One has optically active fluorine-containing alkylallyl amine compounds and preparation method | |
| CN105622544B (en) | A kind of synthetic method of N- sulfonyls -3,4- dihydro -2H-1,4- thiazines | |
| JP4654444B2 (en) | Diamine ligand and catalyst using the same | |
| CN109810056B (en) | S-alkyl-S-quinolyl-N-sulfonyl nitrogen sulfur ylide compound and preparation and application thereof | |
| CN106478721B (en) | Oxazoline oxygen phosphorus organic micromolecule catalyst and preparation method thereof derived from a kind of camphor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |