CN106146417B - A method of 4- aryl-NH-1,2,3- triazole is prepared using aldehyde sodium bisulfite adduct - Google Patents
A method of 4- aryl-NH-1,2,3- triazole is prepared using aldehyde sodium bisulfite adduct Download PDFInfo
- Publication number
- CN106146417B CN106146417B CN201510176953.8A CN201510176953A CN106146417B CN 106146417 B CN106146417 B CN 106146417B CN 201510176953 A CN201510176953 A CN 201510176953A CN 106146417 B CN106146417 B CN 106146417B
- Authority
- CN
- China
- Prior art keywords
- reaction
- mmol
- aldehyde
- sodium
- sodium bisulfite
- 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.)
- Active
Links
- 0 C*(*)C[C@](C)*C(C)=NC Chemical compound C*(*)C[C@](C)*C(C)=NC 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
4- aryl-is prepared using aldehyde sodium bisulfite adduct the present invention relates to a kind ofNHThe method of 1,2,3-triazoles, it is characterized by comprising following steps: aldehyde sodium bisulfite adduct, nitro compound, sodium azide, solvent, additive are reacted 1-10 hours under the conditions of 60-150 DEG C by " one kettle way ", after reaction, post-treated, 4- aryl-can be madeNH- 1,2,3- triazole.The present invention uses aldehyde sodium bisulfite adduct cheap and easy to get, and nitro compound, sodium azide is raw material, three components can easily be prepared 4- aryl-NH- 1,2,3- triazole class compounds.Compared with existing method, this method low in raw material price and simple and easy to get, easy to operate, reaction efficiency height.
Description
Technical field
The present invention relates to a kind of synthetic methods of 1,2,3-triazoles, and in particular to 4- aryl-NH-1, the synthesis of 2,3- triazoles
Method belongs to organic synthesis, pharmaceutical synthesis and organic material field.
Background technique
1,2,3-triazoles is a kind of containing there are three the five member ring heterocyclic compounds of nitrogen-atoms.Currently, 1,2,3-triazoles compound
There is application in many fields, such as can be used for antibacterial in terms of drug, antiviral, antitumor, AntiHIV1 RT activity, anti-epileptic etc., it is also possible to
In fields such as pesticide, dyestuffs.4- aryl-NH-1,2,3- triazoles are one kind special in numerous triazole class compounds, experimental study
Show NH-1,2,3- triazoles have special bioactivity.More documents have studied in detail NH-1,2,3- triazole to indoles amine-
The inhibiting effect of 2,3- dioxygenase (IDO).Meanwhile NH-1,2,3- triazoles have inhibition to live methionine peptase (hMetAP2)
Property.Experiment in vitro shows 4- aryl-NH-1, and 2,3- triazoles also have inhibitory activity to lobulus pulmonis tumour cell.Therefore, such is changed
Close the potential drug that object is a variety of diseases such as the certain cancers for the treatment of, Alzheimer disease, cataract.But such chemical combination at present
The synthetic method of object is by certain limitation, therefore, research and development 4- aryl-NH-1, the preparation side of 2,3- triazole compounds
Method has important value.
In 4- aryl-NH-1, the preparation method of 2,3- triazole compounds, current main method is by alkynes and to fold
The cycloaddition reaction of nitrogen compound or functionalized alkene and reaction of sodium azide.But in these methods, it is required to alkynes
Or alkene, therefore, the raw material of reaction needs special reaction to prepare.These preparation methods limit 4- aryl-NH-1,2,3-
The synthesis of triazole compounds.We have found that aromatic aldehyde, nitro compound and sodium azide under certain condition, can under study for action
NH-12,3- triazole class compounds to be prepared under conditions of one kettle way.This method needs to greatly improve using aldehyde as raw material
The convenience of NH-12,3- triazole class compounds synthesis.Although aldehyde can largely be prepared and synthesizing and separating, by
It is easy to aoxidize and unstable and side reaction that may be present in the reaction in aldehyde itself, part aldehyde has also separation is difficult to ask
Topic, these unfavorable factors limit 4- aryl-NH-1 to a certain extent, the synthesis of 2,3- triazole compounds and more extensive
Using.
Aldehyde sodium bisulfite adduct is the important addition product of one kind that aldehyde and sodium hydrogensulfite are formed, while separating
It is an important intermediate in aldehyde compound.Such as in separation vanillic aldehyde, veratraldehyde, the isolating and purifying of cinnamic acid aldehyde,
Aldehyde sodium bisulfite adduct is important intermediate and is used for separating-purifying.Simultaneously as aldehyde compound is easy to oxidize, protect
It deposits and is applicable in and be affected, and aldehyde bisulfite sodium compound can save for a long time, and easy to use.Another party
Face, the adduct are compared with aldehyde, there is certain variation and difference in reactivity.For these reasons, external multiple researchs
Group development is multiple using aldehyde sodium hydrogensulfite addition product as the reaction of raw material, these reactions achieve good effect.
2013, American scholar Vounatsos developed the reductive amination process of aldehyde sodium bisulfite adduct, and by the reactive applications
In treatment diabetes B medicine DPP-IV inhibitor exploitation, good reaction effect (J. Org. Chem. is achieved
2013,78,1655-1659).Malaysian scholar Yoon is reacted by aldehyde sodium hydrogensulfite with o-phenylenediamine class compound,
Benzimidazole (the Bioorganic Chemistry, 2013,49,33- that there is high inhibitory activity to cholinesterase are synthesized
39).American scholar Ojima is reacted also by aldehyde sodium hydrogensulfite with o-phenylenediamine class compound, has been synthesized to native La Fulangxi
This bacterium have antibacterial activity benzimidazoles compound (Bioorganic & Medicinal Chemistry, 2013,21,
3318-3326).
It in conclusion aldehyde sodium bisulfite adduct has special advantage in synthetic reaction, while being separation aldehydes
Therefore the important intermediate of compound develops and utilizes aldehyde sodium bisulfite adduct to synthesize 4- aryl-NH-1, and 2,3- tri-
The synthetic method of azoles, it will help pushing has the active molecule discovery of good biological and exploitation, facilitates such compound
Convenient synthesis has important economic value and application prospect.
Summary of the invention
The present invention provides 4- aryl-NH-1 shown in a kind of formula (I), and the preparation method of 2,3- triazole class compounds is special
Sign is to include the following steps: that the formula (I) compound passes through aldehyde sodium bisulfite adduct, nitro compound, Azide
Sodium reacts in the presence of solvent, additive to be prepared;Wherein formula (I) compound is as follows
Wherein Ar is C5-C10 aryl (preferably phenyl, naphthalene) or C5-C10 heteroaryl (preferably pyridyl group, thienyl);R2
For hydrogen, C1-C6 alkyl or C1-C6 alkoxy formoxyl, wherein R2Preferably hydrogen, methyl, ethyl, propyl, methoxycarbonyl base, second
Oxygen acetyl group;The aldehyde sodium bisulfite adduct be the C5-C10 aryl formaldehyde being optionally substituted by one or more substituents or
The product of C5-C10 heteroaryl carboxaldehyde and sodium hydrogensulfite addition, the wherein preferred benzaldehyde of aryl formaldehyde, naphthaldehyde, heteroaryl first
The preferred pyridine carboxaldehyde of aldehyde, thiophenecarboxaldehyde, the substituent group are selected from methyl, ethyl, propyl, hydroxyl, chlorine, bromine, fluorine, iodine, nitro, first
Oxygroup, ethyoxyl, phenoxy group, carboxyl, methoxycarbonyl group, carbethoxyl group, amino, dimethylamino, diethylin, acetylamino;Institute
It states nitro compound and is selected from nitro C1-C6 alkyl (preferably nitromethane, nitroethane, nitropropane), nitro C2-C6 carboxylate
(preferably ethyl nitroacetate, nitropropionic acid methyl esters, nitro butyric acid ethyl ester), nitro C2-C6 nitrile (preferably nitroacetonitrile, nitro third
Nitrile, nitro butyronitrile);The additive is selected from anhydrous sodium hydrogensulfite, sodium sulfite, triethylamine, disodium hydrogen phosphate, bicarbonate
The mixing of any one or more of sodium, sodium carbonate, potassium carbonate, sodium acetate.The reaction temperature is 60-150 DEG C, and the reaction time is
1-10 hours.The molar ratio of the aldehyde sodium hydrogensulfite, nitro compound and sodium azide is 1:1-4:1-4, the addition
The mole dosage of agent is 0.1-4 times of aldehyde.The solvent is dimethyl sulfoxide, DMAC N,N' dimethyl acetamide, N, N- dimethyl methyl
Amide, hexamethylphosphoramide, any one or a few the mixed solvent in N-Methyl pyrrolidone.The aldehyde bisulfite
The dosage of sodium adduct and solvent is 1mol aldehyde sodium bisulfite adduct 1-20 L solvent.Reaction raw materials can disposably add
Enter into reactor, can also be added in reactor in batches, after one of or two kinds of additions can also being reacted wherein,
Remaining reagent is added in batches again.Above-mentioned reaction can carry out under nitrogen or inert gas shielding, can also be not required to protection gas
Body.Above-mentioned reaction can also carry out under conditions of additive-free.
The present invention compared with the existing technology the advantages of be:
(1) present invention prepares 4- aryl-NH-1,2,3- triazole by aldehyde sodium bisulfite adduct;Aldehyde sodium hydrogensulfite
Adduct has special property, greatly facilitates 4- aryl-NH-1, the synthesis of 2,3- triazoles.
(2) present invention prepares 4- aryl-NH-1,2,3- triazole by one kettle way;" one kettle way " of the invention is that will own
Reaction raw materials are completed to react with reagent in a reaction flask, do not need to separate intermediate, while above-mentioned " one kettle way "
Reaction, which can be, disposably puts into raw material, is also possible to after reaction flask is added in part material, then be added during the reaction
Remaining raw material is also possible to that a part of raw material is first first added in reaction flask, then remaining original is added during the reaction
Material.
(3) present invention by being added suitable additive (such as sodium bicarbonate, sodium hydrogensulfite, sulfurous in the reaction system
Potassium hydrogen phthalate, sodium dihydrogen phosphate) improve reaction yield.
(4) the features such as present invention is easy to get with raw material, and reaction does not need transition metal participation, easy to operate, high income,
Production efficiency is greatly improved, it is easy to industrialized production.
Specific embodiment:
For the ease of a further understanding of the present invention, examples provided below has done more detailed description to it.But
It is that these embodiments are only not supposed to be a limitation to the present invention or implementation principle for better understanding invention, reality of the invention
The mode of applying is not limited to the following contents.
Embodiment 1:
The synthesis of 4- phenyl-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: 1mmol benzaldehyde sodium bisulfite adduct, 2.0 mmol nitrine are added into 10mL round-bottomed flask
Change sodium, 4.0 mmol nitromethanes and 1.0 mL dimethyl sulfoxides, is heated 4 hours at 120 DEG C.After reaction, reactant
System is cooled to room temperature, and reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate are added, and 30 mL water and 10 mL are saturated chlorine
To change aqueous ammonium, extracts liquid separation, organic phase is washed with water 3 times (10mL * 3), washed once afterwards with saturated salt solution (10mL),
It is dried over anhydrous sodium sulfate again.Desiccant is filtered out, filtrate decompression prolapse solvent, silicagel column column chromatography, eluant, eluent is petroleum ether/second
Acetoacetic ester (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 60%.Nuclear magnetic data: 1HNMR(DMSO-d6): δ=
15.16 (br, 1H), 8.35 (br, 1H), 7.89(m, 2H), 7.47 (m, 2H), 7.36 (t, J = 7.2
Hz, 1H)。
Embodiment 2:
The synthesis of 4- phenyl-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: 1.0 mmol benzaldehyde sodium bisulfite adducts, 1.0 mmol are added into 10mL round-bottomed flask
Sodium azide, 1.0 mmol NaHSO3And 3mL dimethyl sulfoxide, reaction system replace nitrogen, are added dropwise at 60 DEG C and contain 1.0
N,N dimethylformamide (DMF) solution of mmol nitromethane after dripping, continues heating 10 hours.Other operations are the same as implementation
Example 1, yield 42%.
Embodiment 3:
The synthesis of 4- phenyl-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: being added 1.0 mmol benzaldehydes into 10mL round-bottomed flask, 2.0 mmol sodium azide, and 1.0
mmol Na2SO3And 3 mLN- methyl pyrrolidones (NMP), it is molten that the NMP containing 4.0 mmol nitromethanes is added dropwise at 120 DEG C
Liquid (2 mL) after dripping, continues heating 5 hours.Other operations are the same as embodiment 1, yield 45%.
Embodiment 4:
The synthesis of 4- phenyl-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: being added the adduct of 1.0 mmol benzaldehydes and sodium hydrogensulfite into 10mL round-bottomed flask, and 4.0
Mmol sodium azide, 2.0 mmol nitromethanes and 3 mL hexamethylphosphoramide (HMPTA) heat 4 hours in 150 DEG C.Its
He operates with embodiment 1, yield 40%.
Embodiment 5:
The synthesis of 4- p-methylphenyl-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: 1.0 mmol 4- tolyl aldehyde sodium bisulfite adducts being added into 10mL round-bottomed flask,
2.0 mmol sodium azide, 1.0 mmol NaHSO3And 10 mL dimethyl sulfoxides, reaction system replaces nitrogen, at 110 DEG C
The DMSO solution (10 mL) containing 2.0 mmol nitromethanes is added dropwise, after dripping, continues heating 4 hours.After reaction,
Reaction system is cooled to room temperature, and reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate, 30 mL water and 10 mL are added
Saturated aqueous ammonium chloride, extracts liquid separation, and organic phase is washed with water 3 times (10mL * 3), is washed afterwards with saturated salt solution (10mL)
It washs once, then is dried over anhydrous sodium sulfate.Desiccant is filtered out, filtrate decompression prolapse solvent, silicagel column column chromatography, eluant, eluent is stone
Oily ether/ethyl acetate (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 70%.Nuclear magnetic data: 1HNMR(DMSO-
d6): δ=15.06 (br, 1H), 8.27 (br, 1H), 7.74 (d, J=8.0 Hz, 2H), 7.26 (d, J=
8.0 Hz, 2H), 2.32 (s, 3H) 。
Embodiment 6:
The synthesis of 4- (Chloro-O-Phenyl)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: being added 1.0 mmol 2- chlorobenzaldehyde sodium bisulfite adducts into 10mL round-bottomed flask, and 3.0
Mmol sodium azide, 1.0 mmol Na2SO3And 3 mL dimethyl sulfoxides, it is added dropwise at 150 DEG C and contains 2.0 mmol nitromethanes
DMSO solution (2 mL), after dripping, continue heating 2 hours.After reaction, reaction system is cooled to room temperature, reaction solution
It is all transferred in separatory funnel, 30 mL ethyl acetate, 30 mL water and 10 mL saturated aqueous ammonium chlorides is added, extract liquid separation,
Organic phase is washed with water 3 times (10mL * 3), washed once afterwards with saturated salt solution (10mL), then be dried over anhydrous sodium sulfate.
Desiccant is filtered out, filtrate decompression prolapse solvent, silicagel column column chromatography, eluant, eluent is petrol ether/ethyl acetate (v:v=4:1).It receives
Collect fraction, obtains white powder.Yield is 75%.Nuclear magnetic data: 1HNMR(DMSO-d6): δ=15.36 (br, 1H), 8.37
(br, 1H), 7.93 (s, 1H), 7.63-7.55 (m, 1H), 7.50-7.37 (m, 2H)。
Embodiment 7:
The synthesis of 4- (o-hydroxy-phenyl)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: 1.0 mmol salicylaldhyde sodium bisulfite adducts being added into 10 mL round-bottomed flasks,
2.0 mmol sodium azide, 2.0 mmol Na2SO3And 3mL dimethyl sulfoxide, reaction system are replaced nitrogen, are added dropwise at 100 DEG C
DMSO solution (1 mL) containing 4.0 mmol nitromethanes after dripping, continues heating 2 hours.After reaction, reactant
System is cooled to room temperature, and reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate are added, and 30 mL water and 10 mL are saturated chlorine
To change aqueous ammonium, extracts liquid separation, organic phase is washed with water 3 times (10mL * 3), washed once afterwards with saturated salt solution (10mL),
It is dried over anhydrous sodium sulfate again.Desiccant is filtered out, filtrate decompression prolapse solvent, silicagel column column chromatography, eluant, eluent is petroleum ether/second
Acetoacetic ester (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 45%.Nuclear magnetic data: 1H-NMR(DMSO-d6): δ=
15.15 (br, 1H), 10.18 (br, 1H), 8.27 (br, 1H), 7.89 (s, 1H), 7.25-7.13 (m,
1H), 7.05-6.95 (m, 1H), 6.95-6.83 (m, 1H)。
Embodiment 8:
The synthesis of 4- (o- methoxyphenyl)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: 1.0 mmol o- methoxybenzaldehyde sodium hydrogensulfite adductions are added into 10 mL round-bottomed flasks
Object, 3.0 mmol sodium azide, 1.0 mmol NaHSO3, 1.0 mmol sodium hydrogensulfites and 3 mL dimethyl sulfoxides, reactant
System's displacement nitrogen, is added dropwise the DMSO solution (1 mL) containing 2.0 mmol nitromethanes at 110 DEG C, after dripping, continues to add
Heat 8 hours.After reaction, reaction system is cooled to room temperature, and reaction solution is all transferred in separatory funnel, and 30 mL acetic acid are added
Ethyl ester, 30 mL water and 10 mL saturated aqueous ammonium chlorides extract liquid separation, and organic phase is washed with water 3 times (10mL * 3), rear to use
Saturated salt solution (10mL) washed once, then be dried over anhydrous sodium sulfate.Filter out desiccant, filtrate decompression prolapse solvent, silica gel
Column column chromatography, eluant, eluent are petrol ether/ethyl acetate (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 76%.Nuclear-magnetism
Data: 1H-NMR (DMSO-d6): δ = 15.17 (br, 1H), 8.22 (br, 1H), 8.03 (br, 1H),
7.15 (d, J = 8.4 Hz, 1H), 7.06 (t, J = 8.4 Hz, 1H), 3.92 (s, 3H)。
Embodiment 9:
The synthesis of 4- (p-bromophenyl)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: being added 1.0 mmol 4- bromobenzaldehyde sodium bisulfite adducts into 10 mL round-bottomed flasks, and 3.0
Mmol sodium azide, 2.0 mmol NaHSO3, 2.0 mmol sodium dihydrogen phosphates and 3 mL dimethyl sulfoxides, reaction system are replaced
The DMSO solution (1 mL) containing 4.0 mmol nitromethanes is added dropwise in nitrogen at 100 DEG C, and after dripping, it is small to continue heating 8
When.After reaction, reaction system is cooled to room temperature, and reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate are added,
30 mL water and 10 mL saturated aqueous ammonium chlorides extract liquid separation, and organic phase is washed with water 3 times (10mL * 3), rear saturation
Saline solution (10mL) washed once, then be dried over anhydrous sodium sulfate.Filter out desiccant, filtrate decompression prolapse solvent, silicagel column column
Chromatography, eluant, eluent are petrol ether/ethyl acetate (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 73%.Nuclear-magnetism number
According to: 1HNMR(DMSO-d6): δ=15.23 (br, 1H), 8.41 (br, 1H), 7.90-7.80 (m, 2H),
7.70-7.60 (m, 2H)。
Embodiment 10:
The synthesis of 4- (Alpha-Naphthyl)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: being added 1.0 mmol α-naphthaldehyde sodium bisulfite adduct into 10mL round-bottomed flask, and 4.0
Mmol sodium azide, 2.0 mmol NaHSO3And 3 mL dimethyl sulfoxides, reaction system replace nitrogen, are added dropwise and contain at 100 DEG C
There is the DMSO solution (1 mL) of 2.0 mmol nitromethanes, after dripping, continues heating 4 hours.After reaction, reaction system
It is cooled to room temperature, reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate are added, and 30 mL water and 10 mL are saturated chlorination
Aqueous ammonium extracts liquid separation, and organic phase is washed with water 3 times (10mL * 3), washed once afterwards with saturated salt solution (10mL), then
It is dried over anhydrous sodium sulfate.Desiccant is filtered out, filtrate decompression prolapse solvent, silicagel column column chromatography, eluant, eluent is petroleum ether/acetic acid
Ethyl ester (v: v=4: 1).Fraction is collected, white powder is obtained.Yield is 69%.Nuclear magnetic data: 1HNMR (DMSO-d6): δ
= 15.34 (br, 1H), 8.48 (br, 1H), 8.31 (br, 1H), 8.05-7.95 (m, 2H), 7.77(d, J
= 6.8 Hz, 1H), 7.70-7.60 (m, 3H)。
Embodiment 11:
The synthesis of 4- (p-trifluoromethyl phenyl)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: 1.0 mmol 4- trifluoromethylated benzaldehyde sodium hydrogensulfite adductions are added into 10mL round-bottomed flask
Object, 4.0 mmol sodium azide, 2.0 mmol NaHSO3And 3 mL dimethyl sulfoxides, reaction system replaces nitrogen, in 100 DEG C
Lower DMSO solution of the dropwise addition containing 4.0 mmol nitromethanes after dripping, continues heating 4 hours.After reaction, reactant
System is cooled to room temperature, and reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate are added, and 30 mL water and 10 mL are saturated chlorine
To change aqueous ammonium, extracts liquid separation, organic phase is washed with water 3 times (10mL * 3), washed once afterwards with saturated salt solution (10mL),
It is dried over anhydrous sodium sulfate again.Desiccant is filtered out, filtrate decompression prolapse solvent, silicagel column column chromatography, eluant, eluent is petroleum ether/second
Acetoacetic ester (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 62%.Nuclear magnetic data: 1HNMR(DMSO-d6): δ=
15.35 (br, 1H), 8.54 (br, 1H), 8.09 (d, J = 8.8 Hz, 2H), 7.83(d, J = 8.8 Hz,
2H)。
Embodiment 12:
5- ethyl -4- phenyl-NH-1,2,3- triazole
Reaction equation are as follows:
Specific steps: 1.0 mmol benzaldehyde sodium bisulfite adducts, 4.0 mmol are added into 10mL round-bottomed flask
Sodium azide, 2.0 mmol Na2SO3And 3 mL dimethyl sulfoxides, reaction system replace nitrogen, are added dropwise at 100 DEG C and contain 4.0
The DMSO solution (1 mL) of mmol nitropropane after dripping, continues heating 10 hours.After reaction, reaction system is cooling
To room temperature, reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate, 30 mL water and 10 mL saturated ammonium chloride water are added
Solution, extracts liquid separation, and organic phase is washed with water 3 times (10mL * 3), washed once afterwards with saturated salt solution (10mL), then through nothing
Aqueous sodium persulfate is dry.Desiccant is filtered out, filtrate decompression prolapse solvent, silicagel column column chromatography, eluant, eluent is petrol ether/ethyl acetate
(v:v=4:1).Fraction is collected, white powder is obtained.Yield is 55%.Nuclear magnetic data: 1HNMR(DMSO-d6): δ=14.88
(br, 1H), 7.69 (d, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.38 (t, J =
7.6 Hz, 1H), 2.87 (q, J = 7.6 Hz, 2H), 1.25 (t, J = 7.6 Hz, 3H)。
Embodiment 13:
4- (3- pyridyl group)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: being added 1.0 mmol 3- pyridine carboxaldehyde sodium bisulfite adducts into 10mL round-bottomed flask, and 2.0
Mmol sodium azide, 1.0 mmol Na2SO3And 3 mL dimethyl sulfoxides, reaction system replace nitrogen, are added dropwise and contain at 150 DEG C
There is the DMSO solution (1 mL) of 2.0 mmol nitromethanes, after dripping, continues heating 6 hours.After reaction, reaction system
It is cooled to room temperature, reaction solution is all transferred in separatory funnel, and 30 mL ethyl acetate are added, and 30 mL water and 10 mL are saturated chlorination
Aqueous ammonium extracts liquid separation, and organic phase is washed with water 3 times (10mL * 3), washed once afterwards with saturated salt solution (10mL), then
It is dried over anhydrous sodium sulfate.Desiccant is filtered out, filtrate decompression prolapse solvent, silica gel column chromatography, eluant, eluent is petroleum ether/acetic acid second
Ester (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 65%.Nuclear magnetic data: 1HNMR 1H NMR (DMSO-d6 ):
δ = δ 15.36 (br, 1H), 9.10 (s, 1H), 8.60-8.50 (m, 1H), 8.47 (s, 1H), 8.29-
8.17 (m, 8.0 Hz, 1H), 7.55-7.40 (m, 1H)。
Embodiment 14:
4- (2- thienyl)-NH-1,2,3- triazole:
Reaction equation are as follows:
Specific steps: being added 1.0 mmol 2 thiophene carboxaldehyde sodium bisulfite adducts into 10mL round-bottomed flask, and 2.0
Mmol sodium azide, 1.0 mmol Na2SO3And 3 mLN- methylpyrrolidone solutions (NMP), reaction system replace nitrogen, in
The N-Methyl pyrrolidone solution (2 mL) containing 2.0 mmol nitromethanes is added dropwise at 100 DEG C, after dripping, continues heating 8
Hour.After reaction, reaction system is cooled to room temperature, and reaction solution is all transferred in separatory funnel, and 30 mL acetic acid second are added
Ester, 30 mL water and 10 mL saturated aqueous ammonium chlorides extract liquid separation, and organic phase is washed with water 3 times (10mL * 3), rear with full
It washed once, then be dried over anhydrous sodium sulfate with saline solution (10mL).Filter out desiccant, filtrate decompression prolapse solvent, silicagel column
Chromatography, eluant, eluent are petrol ether/ethyl acetate (v:v=4:1).Fraction is collected, white powder is obtained.Yield is 52%.Nuclear-magnetism number
According to: 1HNMR (DMSO-d6): δ = 15.18 (br, 1H), 8.27 (m, 1H), 7.57-7.52 (m, 2H),
7.17-7.15 (m, 1H)。
Claims (3)
1. 4- aryl-NH-1 shown in a kind of formula (I), the preparation method of 2,3- triazole class compounds, it is characterised in that including such as
Lower step: formula (I) compound is by aldehyde sodium bisulfite adduct, nitro compound, sodium azide in solvent, addition
Reaction is prepared in the presence of agent;Wherein formula (I) compound is selected from
The aldehyde sodium bisulfite adduct is selected from
The nitro compound is nitromethane;
The additive is selected from one of anhydrous sodium hydrogensulfite, sodium sulfite;
The solvent is in dimethyl sulfoxide, N,N-dimethylformamide, hexamethylphosphoramide, N-Methyl pyrrolidone
Any one.
2. preparation method described in claim 1, it is characterised in that reaction temperature is 60-150 DEG C, and the reaction time is that 1-10 is small
When.
3. the described in any item preparation methods of claim 1-2, it is characterised in that the aldehyde sodium bisulfite adduct, nitro
The molar ratio of compound and sodium azide is 1:1-4:1-4;The mole dosage of the additive is aldehyde sodium bisulfite adduct
0.1-4 times.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510176953.8A CN106146417B (en) | 2015-04-15 | 2015-04-15 | A method of 4- aryl-NH-1,2,3- triazole is prepared using aldehyde sodium bisulfite adduct |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510176953.8A CN106146417B (en) | 2015-04-15 | 2015-04-15 | A method of 4- aryl-NH-1,2,3- triazole is prepared using aldehyde sodium bisulfite adduct |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106146417A CN106146417A (en) | 2016-11-23 |
CN106146417B true CN106146417B (en) | 2018-12-04 |
Family
ID=57336854
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510176953.8A Active CN106146417B (en) | 2015-04-15 | 2015-04-15 | A method of 4- aryl-NH-1,2,3- triazole is prepared using aldehyde sodium bisulfite adduct |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106146417B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106146418B (en) * | 2015-04-19 | 2018-12-04 | 海南师范大学 | A kind of synthetic method of NH-1,2,3- triazole compounds |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103058942A (en) * | 2012-12-20 | 2013-04-24 | 江苏城市职业学院 | One-pot synthetic method for 1,2,3-triazole compounds |
-
2015
- 2015-04-15 CN CN201510176953.8A patent/CN106146417B/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103058942A (en) * | 2012-12-20 | 2013-04-24 | 江苏城市职业学院 | One-pot synthetic method for 1,2,3-triazole compounds |
Non-Patent Citations (2)
Title |
---|
A Metal-Free Three-Component Reaction for the Regioselective Synthesis of 1,4,5-Trisubstituted 1,2,3-Triazoles;Joice Thomas et al.;《Angew. Chem. Int. Ed.》;20140702;第53卷(第38期);第10155-10159页 * |
Xue-Jing Quan et al..p‑Toluenesulfonic Acid Mediated 1,3-Dipolar Cycloaddition of Nitroolefins with NaN3 for Synthesis of 4‑Aryl-NH-1,2,3-triazoles.《Organic Letters》.2014,第16卷第5728-5731页. * |
Also Published As
Publication number | Publication date |
---|---|
CN106146417A (en) | 2016-11-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Maldonado et al. | Synthesis and arylation of unprotected sulfonimidamides | |
WO2020147861A1 (en) | Electrochemical preparation method for β-trifluoromethylamide compound | |
CN105001031B (en) | Ionic iron (III) coordination compound containing single phenol functionalization Imidazole cation and preparation method and application | |
CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
CN106866528A (en) | A kind of method for preparing 4 amino quinoline derivatives | |
CN103113293B (en) | Polysubstituted quinoline derivative and preparation method thereof | |
CN107540598B (en) | Method for preparing N-difluoromethylthio phthalimide compound | |
CN106146417B (en) | A method of 4- aryl-NH-1,2,3- triazole is prepared using aldehyde sodium bisulfite adduct | |
CN107118215B (en) | A kind of preparation method for treating breast cancer medicines Rui Boxini intermediate | |
CN106866707B (en) | A kind of preparation method of benzimidazole simultaneously [2,1-b] thiazole | |
CN110204464B (en) | Synthesis method of aryl tertiary sulfonamide compound | |
CN110294730B (en) | Difluoromethyl sulfuration flavonoid compound and preparation method thereof | |
CN117105845A (en) | Electrophilic trifluoro methyl selenizing reagent and preparation method and application thereof | |
CN110483387A (en) | A kind of method of one pot process nicotimine amide derivatives | |
CN110511193A (en) | A kind of α -one thioamide analog compound and its synthetic method | |
CN103204803A (en) | Method used for synthesizing etoricoxib | |
CN106146418B (en) | A kind of synthetic method of NH-1,2,3- triazole compounds | |
CN108794375A (en) | A kind of pabishta intermediate and its synthesis and application | |
CN110642689B (en) | 3, 6-dibromo-2-methylbenzaldehyde and chemical synthesis method thereof | |
CN111018807B (en) | Method for synthesizing 1,2, 4-thiadiazole derivative | |
CN107163036A (en) | One kind is containing assimilation compound of 5,6 disubstituted pyridines of thiazole ring 2 and preparation method thereof | |
CN108440373B (en) | Iron-catalyzed cyanoalkylindoline and preparation method thereof | |
CN106749038A (en) | A kind of preparation method of flibanserin | |
CN111285880A (en) | Preparation and application of switch compound containing bisprown ether | |
CN104136422A (en) | Compound, method for producing compound, and method for purifying compound |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |