CN116641073A - Method for electrochemically synthesizing N- (alpha-alkoxyalkyl) azole compound - Google Patents
Method for electrochemically synthesizing N- (alpha-alkoxyalkyl) azole compound Download PDFInfo
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- -1 azole compound Chemical class 0.000 title claims abstract description 61
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title abstract description 11
- 238000000034 method Methods 0.000 title abstract description 11
- 230000002194 synthesizing effect Effects 0.000 title abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 50
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 10
- 150000003851 azoles Chemical class 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 50
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 46
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 44
- 239000000758 substrate Substances 0.000 claims description 26
- 239000003208 petroleum Substances 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 25
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 23
- 238000004440 column chromatography Methods 0.000 claims description 23
- 238000004090 dissolution Methods 0.000 claims description 23
- 229910052697 platinum Inorganic materials 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 23
- 238000004809 thin layer chromatography Methods 0.000 claims description 23
- 229910052786 argon Inorganic materials 0.000 claims description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 5
- 150000001299 aldehydes Chemical class 0.000 claims description 5
- 239000012964 benzotriazole Substances 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000001308 synthesis method Methods 0.000 claims description 5
- 150000003934 aromatic aldehydes Chemical class 0.000 claims description 4
- 239000003792 electrolyte Substances 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 238000012544 monitoring process Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 239000003377 acid catalyst Substances 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 abstract description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 2
- 150000003254 radicals Chemical class 0.000 abstract 2
- 150000001298 alcohols Chemical class 0.000 abstract 1
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 230000018044 dehydration Effects 0.000 abstract 1
- 238000006297 dehydration reaction Methods 0.000 abstract 1
- 150000002831 nitrogen free-radicals Chemical class 0.000 abstract 1
- 239000007800 oxidant agent Substances 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 42
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000010828 elution Methods 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 21
- 230000035484 reaction time Effects 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 238000012512 characterization method Methods 0.000 description 20
- 239000007788 liquid Substances 0.000 description 20
- YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical compound O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 description 8
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N phenyl propionaldehyde Natural products CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 8
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 6
- 238000010490 three component reaction Methods 0.000 description 4
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 3
- YGHRJJRRZDOVPD-UHFFFAOYSA-N 3-methylbutanal Chemical compound CC(C)CC=O YGHRJJRRZDOVPD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 150000001565 benzotriazoles Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- NEHNMFOYXAPHSD-UHFFFAOYSA-N citronellal Chemical compound O=CCC(C)CCC=C(C)C NEHNMFOYXAPHSD-UHFFFAOYSA-N 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- KSMVZQYAVGTKIV-UHFFFAOYSA-N decanal Chemical compound CCCCCCCCCC=O KSMVZQYAVGTKIV-UHFFFAOYSA-N 0.000 description 2
- 150000002373 hemiacetals Chemical class 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- NUJGJRNETVAIRJ-UHFFFAOYSA-N octanal Chemical compound CCCCCCCC=O NUJGJRNETVAIRJ-UHFFFAOYSA-N 0.000 description 2
- 230000033116 oxidation-reduction process Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- MQBIZQLCHSZBOI-UHFFFAOYSA-N 4-(4-Methyl-3-pentenyl)-3-cyclohexene-1-carboxaldehyde Chemical compound CC(C)=CCCC1=CCC(C=O)CC1 MQBIZQLCHSZBOI-UHFFFAOYSA-N 0.000 description 1
- LRUDIIUSNGCQKF-UHFFFAOYSA-N 5-methyl-1H-benzotriazole Chemical compound C1=C(C)C=CC2=NNN=C21 LRUDIIUSNGCQKF-UHFFFAOYSA-N 0.000 description 1
- MARUHZGHZWCEQU-UHFFFAOYSA-N 5-phenyl-2h-tetrazole Chemical compound C1=CC=CC=C1C1=NNN=N1 MARUHZGHZWCEQU-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 239000011831 acidic ionic liquid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229930003633 citronellal Natural products 0.000 description 1
- 235000000983 citronellal Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000002265 redox agent Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/05—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/07—Oxygen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/09—Nitrogen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Catalysts (AREA)
Abstract
The invention discloses an electrochemical synthesisN‑(αMethod for synthesizing (E) -alkoxyalkyl) azole compound by reaction of three components of azole, aldehyde and alcohol under mild electrochemical conditionN‑(αAlkoxyalkyl) azole compounds, i.e. in the electrolytic process, the azoles are oxidized at the anode to form nitrogen radicals, while the aldehydes are reduced at the cathode to form hydroxyalkyl radicals, which are then coupled by radicals, and finally intermolecular dehydration with alcohols to form a series of compoundsN‑(α-alkoxyalkyl) azole compounds. The reaction avoids the use of an acid catalyst, an additional oxidant and a reducing agent through a free radical active intermediate route, and has low production cost and environmental friendliness. And gram-scale amplifierThe feasibility of the results of the large experiments indicates that the method is suitable for industrial mass production.
Description
Technical Field
The invention relates to an electrochemical synthesis technology, in particular to a method for synthesizing an N- (alpha-alkoxy alkyl) azole compound by electrochemical three-component reaction.
Background
The synthesis and functionalization of nitrogen-containing heterocycles in organic chemistry is a common and attractive area of research, as they find wide application in pharmaceutical chemistry, agriculture, and materials science. Among them, benzotriazole is a unique class of nitrogen-containing heterocyclic compounds, and N-substituted benzotriazole has good biological properties (Eur.J.Med.Chem.2015, 97,612;J.Chem.Pharm.Res.2011,3,375;J.Heterocyclic Chem.2023,60,705;Front.Chem.2021,9,660424) in the pharmaceutical industry, including antibacterial, antitumor, antiviral, antiprotozoal, plant growth regulator, anti-inflammatory activity, and the like. Thus, N-substituted benzotriazoles have attracted considerable attention from pharmaceutical chemists.
At present, in the research work on N-substituted benzotriazoles, C (sp 2 ) The N bond has made great progress. But due to C (sp) 3 ) The relative inertness of the H bond, the requirement for the activation energy of the substrate is high, so that direct C (sp 3 ) Construction of C (sp) by amination of H 3 ) The N bond still faces challenges.
N- (alpha-alkoxyalkyl) benzotriazoles as a class consisting of C (sp 3 ) N-substituted benzotriazoles built with N-bonds, the traditional synthetic method is by acid catalyzed synthesis (chi.j.chem.2007, 25,1041; chin.chem.lett.2005,16,155; j.org.chem.1995,60,7619; J.chem.Soc.Perkin Trans 1987,791). Firstly, aldehyde and alcohol undergo nucleophilic addition under acidic condition to form hemiacetal, then the active hydroxyl group of hemiacetal reacts with H + In combination, one molecule of water is stripped off to give a positively charged alkoxyalkyl hemiacetal. Finally, the generated carbocation is added to the N atom of the benzotriazole to obtain the N- (alpha-alkoxyalkyl) benzotriazole. Although this strategy implements C (sp 3 ) The construction of the N bond has some limitations, such as the need of strong acid and long reflux time, poor stability of the acid catalyst, high production cost, easy production of by-product acetal under acidic condition, poor reaction selectivity, and toxicity and difficult biodegradation of some used acidic ionic liquids. Therefore, there is an urgent need to develop an economical and environmentally friendly compact synthetic route to solve these shortcomings.
Disclosure of Invention
The invention aims at overcoming the defects of the prior art and provides a method for synthesizing an N- (alpha-alkoxyalkyl) azole compound by electrochemical three-component reaction. The method has the advantages of no need of acid catalyst and redox agent, low production cost, environmental protection and feasibility of gram-scale amplification experiments, and is suitable for industrial mass production.
The technical scheme for realizing the aim of the invention is as follows:
a method for synthesizing N- (alpha-alkoxyalkyl) azole compounds by electrochemical three-component reaction, wherein the synthetic general formula of the compounds is as follows:
in the general formula, R 1 An alkyl group; r is R 2 Alkyl, aryl; r is R 3 An alkyl group;
the aldehyde is aliphatic aldehyde and aromatic aldehyde; the alcohol is chain alcohol;
the electrolyte is as follows: tetrabutylammonium tetrafluoroborate or tetrabutylammonium hexafluorophosphate;
the solvent is as follows: methanol, ethanol, isopropanol, t-butanol or n-pentanol.
The method for synthesizing the N- (alpha-alkoxyalkyl) azole compound by the electrochemical three-component reaction comprises the following steps:
benzotriazole (0.6 mmol), aliphatic and aromatic aldehydes (2.4 mmol), chain alcohol (6 mL), electrolyte (0.6 mmol) were added separately to a 10mL three-necked round bottom flask;
alcohol is a reaction substrate and is also dissolved as a solvent, platinum sheets (1 cm x 1 cm) are used as an anode and a cathode, stirring reaction is carried out under the protection of argon and at 60 ℃ by using 12mA constant current, and the reaction progress is monitored by adopting thin layer chromatography until the substrate is completely consumed;
after the reaction is completed, the crude product is obtained by decompressing and concentrating, and the concentrated solution is purified by 300-400 mesh silica gel column chromatography to obtain the target product.
The column chromatography purification adopts petroleum ether/ethyl acetate as an eluent, wherein the volume ratio of petroleum ether/ethyl acetate is 15:1.
During synthesis, the raw materials can be added according to the ratio of the raw materials in the synthesis method.
N- (a-alkoxyalkyl) benzotriazoles have important biochemical and antitumor activities (Tetrahedron lett.1968,38,4089;Synthesis 1994,597) and thus have synthetic utility.
The synthesis method of the invention synthesizes the N- (alpha-alkoxyalkyl) azole compound by reacting the three components of the azole, the aldehyde and the alcohol under the mild electrochemical condition. The synthesis method avoids the use of an acid catalyst and an additional oxidation-reduction agent, and has the characteristics of mild reaction conditions, simplicity in operation, low production cost, high controllability and the like. Further, further enlargement of the use of gram-scale electrochemical reactor has shown that it is suitable for industrial mass production.
Detailed Description
The following describes the invention in more detail with reference to examples, but is not intended to limit the invention.
Example 1:
preparation and characterization of 1- (1-ethoxy-3-phenylpropyl) -1H-benzo [ d ] [1,2,3] triazole (4 aaa):
benzotriazol (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aaa.
The product was characterized as:
yellow liquid(143.5mg,85％). 1 H NMR(400MHz,Chloroform-d)δ8.08(dd,J＝8.3,1.1,
1H),7.77(dt,J＝8.3,1.0,1H),7.49-7.45(m,1H),7.40-7.36(m,1H),7.29-7.25(m,2H),7.20-7.14(m,3H),6.03(t,J＝6.6,1H),3.53-3.46(m,1H),3.31-3.24(m,1H),2.78-2.70(m,1H),2.65-2.57(m,2H),2.47-2.40(m,1H),1.14(t,J＝7.0,3H). 13 C NMR(100MHz,Chloroform-d)δ146.89,140.15,131.47,128.63,128.52,127.56,126.37,124.32,120.20,111.29,89.91,64.71,36.26,31.11,14.82.HRMS(m/z)[ESI]:calculated for C 17 H 20 N 3 O + m/z[M+H] + :282.1601,found282.1611。
example 2:
preparation and characterization of 1- (1-ethoxy-3-phenylpropyl) -5-methyl-1H-benzo [ d ] [1,2,3] triazole (4 baa):
5-Methylbenzotriazol (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4baa.
The product was characterized as:
yellow liquid(136.5mg,77％)dr 1:1,as an inseparable diastereomeric mixture. 1 H NMR(500MHz,DMSO-d 6 )δ7.96(d,J＝8.5,0.47H),7.86(t,J＝1.7,0.53H),7.82(d,J＝8.5,0.53H),7.72(t,J＝1.7,0.47H),7.41-7.39(m,0.51H),7.28-7.25(m,2.49H),7.19-7.15(m,3H),6.08(d,J＝6.5,0.51H),6.05(d,J＝6.5,0.49H),3.50-3.44(m,1H),3.17-3.08(m,1H),2.69-2.61(m,1H),2.60-2.53(m,1H),2.50(s,3H),2.47-2.45(m,2H),1.03(q,J＝7.1,3H). 13 C NMR(126MHz,DMSO-d 6 )δ146.39,144.45,140.30,137.98,133.99,132.04,130.05,129.79,128.41,128.30,128.27,126.50,126.07,118.98,118.30,110.81,110.23,88.44,88.35,63.87,63.85,35.42,35.31,30.51,30.45,21.47,20.95,14.62.HRMS(m/z)[ESI]:calculated for C 18 H 22 N 3 O + m/z[M+H] + :296.1757,found 296.1750。
example 3:
preparation and characterization of 1- (1-ethoxy-3-phenylpropyl) -5, 6-dimethyl-1H-benzo [ d ] [1,2,3] triazole (4 caa):
5, 6-Dibenzotriazol (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4caa.
The product was characterized as:
yellow liquid(139.2mg,75％). 1 H NMR(500MHz,Chloroform-d)δ7.86(s,1H),7.57(s,1H),7.33(t,J＝7.7,2H),7.26-7.20(m,3H),6.02(t,J＝6.6,1H),3.56-3.50(m,1H),3.35-3.29(m,1H),2.79-2.73(m,1H),2.68-2.68(m,2H),2.47(d,J＝8.2,7H),1.19(t,J＝7.0,3H). 13 CNMR(126MHz,Chloroform-d)δ146.17,140.28,137.94,134.17,130.47,128.63,128.57,126.36,119.22,110.66,89.66,64.61,36.14,31.17,21.06,20.56,14.86.HRMS(m/z)[ESI]:calculated for C 19 H 24 N 3 O + m/z[M+H] + :310.1914,found 310.1914。
example 4:
preparation and characterization of 2- (1-ethoxy-3-phenylpropyl) -5-phenyl-2H-tetrazole (4 daa):
5-phenyl tetrazole (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4daa.
The product was characterized as:
yellow liquid(116.6mg,63％). 1 H NMR(400MHz,Chloroform-d)δ8.22-8.19(m,2H),7.52-7.48(m,3H),7.33-7.29(m,2H),7.24-7.18(m,3H),5.85(t,J＝6.2,1H),3.62-3.54(m,1H),3.50-3.42(m,1H),2.69(qd,J＝15.1,14.1,6.8,3H),2.57-2.46(m,1H),1.20(t,J＝7.0,3H). 13 C NMR(100MHz,Chloroform-d)δ165.50,140.00,130.58,129.02,128.76,128.59,127.42,127.12,126.52,91.64,65.65,36.00,30.82,14.77.HRMS(m/z)[ESI]:calculated for C 18 H 20 N 4 NaO + m/z[M+Na] + :331.1529,found 331.1524。
example 5:
preparation and characterization of 1- (cyclohexyl (ethoxy) methyl) -1H-benzo [ d ] [1,2,3] triazole (4 aba):
benzotriazol (0.6 mmol), cyclohexyl formaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aba.
The product was characterized as:
yellow liquid(121.4mg,78％). 1 H NMR(400MHz,Chloroform-d)δ8.06(dt,J＝8.3,1.0,1H),
7.77(dt,J＝8.3,1.0,1H),7.47-7.43(m,1H),7.38-7.34(m,1H),5.69(d,J＝8.6,1H),3.51-3.43(m,1H),3.33-3.25(m,1H),2.26-2.14(m,2H),1.84-1.75(m,1H),1.66-1.55(m,2H),1.13(t,J＝7.0,6H),1.00-0.84(m,2H). 13 C NMR(100MHz,Chloroform-d)δ146.81,131.68,127.39,124.21,120.07,111.60,65.00,29.45,27.95,26.13,25.52,25.42,14.75.HRMS(m/z)[ESI]:calculated for C 15 H 22 N 3 O + m/z[M+H] + :260.1757,found 260.1757。
example 6:
preparation and characterization of 1- (cyclopropyl (ethoxy) methyl) -1H-benzo [ d ] [1,2,3] triazole (4 aca):
benzotriazol (0.6 mmol), cyclopropylaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aca.
The product was characterized as:
yellow liquid(106.9mg,82％). 1 H NMR(500MHz,DMSO-d 6 )δ8.08(dt,J＝8.4,0.9,1H),
7.97(dt,J＝8.3,0.9,1H),7.57-(m,1H),7.43-7.40(m,1H),5.62(d,J＝7.7,1H),3.51-3.45(m,1H),3.17-3.11(m,1H),1.79-1.73(m,1H),1.01(t,J＝7.0,3H),0.81-0.69(m,2H),0.47-0.40(m,1H),0.31(td,J＝9.5,5.4,1H). 13 C NMR(126MHz,DMSO-d 6 )δ145.74,131.45,127.61,124.23,119.36,111.45,92.19,63.81,15.15,14.54,3.96,1.83.HRMS(m/z)[ESI]:calculated for C 12 H 16 N 3 O + m/z[M+H] + :218.1288,found 218.1297。
example 7:
preparation and characterization of 1- (1-ethoxy-3-methylbutyl) -1H-benzo [ d ] [1,2,3] triazole (4 ada):
benzotriazol (0.6 mmol), 3-methylbutyraldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4ada.
The product was characterized as:
yellow liquid(99.4mg,71％). 1 H NMR(400MHz,Chloroform-d)δ8.07(dt,J＝8.4,1.0,1H),
7.78(dt,J＝8.3,1.0,1H),7.49-7.45(m,1H),7.40-7.36(m,1H),6.13(t,J＝6.9,1Hzz),3.55-3.47(m,1H),3.29-3.22(m,1H),2.20-2.13(m,1H),2.01 -1.95(m,1H),1.61-1.51(m,1H),1.13(t,J＝7.0,3H),1.00(d,J＝6.7,3H),0.89(d,J＝6.7,3H). 13 C NMR(100MHz,Chloroform-d)δ146.93,131.41,127.49,124.29,120.19,111.44,89.68,64.64,43.43,24.57,22.54,22.41,14.86.HRMS(m/z)[ESI]:calculated for C 13 H 20 N 3 O + m/z[M+H] + :234.1601,found234.1621。
example 8:
preparation and characterization of 1- (1-ethoxy-2, 2-dimethylpropyl) -1H-benzo [ d ] [1,2,3] triazol 4 aea):
benzotriazol (0.6 mmol), 2-dimethylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4aea.
The product was characterized as:
yellow liquid(95.2mg,68％). 1 H NMR(400MHz,Chloroform-d)δ8.05(dd,J＝8.3,1.0,1H),
7.79(dt,J＝8.4,1.0,1H),7.46-7.41(m,1H),7.37-7.33(m,1H),5.73(s,1H),3.48-3.40(m,1H),3.36–3.29(m,1H),1.18(t,J＝7.0,3H),1.03(s,9H). 13 C NMR(100MHz,Chloroform-d)δ146.23,132.70,127.30,123.99,119.81,112.91,98.85,65.76,37.99,25.99,14.70.HRMS(m/z)[ESI]:calculated for C 13 H 20 N 3 O + m/z[M+H] + :234.1601,found 234.1621。
example 9:
preparation and characterization of 1- (1-ethoxyoctyl) -1H-benzo [ d ] [1,2,3] triazole (4 afa):
benzotriazol (0.6 mmol), n-octanal (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4afa.
The product was characterized as:
yellow liquid(132.2mg,80％). 1 H NMR(400MHz,Chloroform-d)δ8.06(dd,J＝8.3,1.1,
1H),7.78(dt,J＝8.3,1.1,1H),7.48-7.4(m,1H),7.39-7.35(m,1H),6.04(t,J＝6.8,1H),3.54-3.46(m,1H),3.30-3.22(m,1H),2.29-2.20(m,1H),2.15-2.06(m,1H),1.44-1.41(m,1H),1.29-1.18(m,8H),1.12(t,J＝7.0,4H),0.83(t,J＝6.9,3H). 13 C NMR(100MHz,Chloroform-d)δ＝146.90,131.37,127.46,124.26,120.15,111.41,91.01,64.66,34.85,31.73,29.08,29.02,24.92,22.66,14.82,14.14.HRMS(m/z)[ESI]:calculated for C 16 H 26 N 3 O + m/z[M+H] + :276.2070,found276.2073。
example 10:
preparation and characterization of 1- (1-ethoxydecyl) -1H-benzo [ d ] [1,2,3] triazole (4 aga):
benzotriazol (0.6 mmol), decanal (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aga.
The product was characterized as:
yellow liquid(169.1mg,85％). 1 H NMR(500MHz,Chloroform-d)δ8.02(d,J＝8.3,1H),
7.75(d,J＝8.3,1H),7.43-7.40(m,1H),7.34-7.31(m,1H),6.01(t,J＝6.8,1H),3.50-3.44(m,1H),3.26-3.19(m,1H),2.25-2.18(m,1H),2.11-2.04(m,1H),1.42-1.33(m,1H),1.29-1.19(m,16H),1.08(t,J＝7.0,4H),0.81(t,J＝6.9,3H). 13 C NMR(126MHz,Chloroform-d)δ146.81,131.30,127.33,124.13,120.05,111.29,90.88,64.53,34.75,31.90,29.56,29.44,29.32,28.96,24.82,22.68,14.72,14.11.HRMS(m/z)[ESI]:calculated for C 20 H 34 N 3 O + m/z[M+H] + :323.2696,found 323.2696。
example 11:
preparation and characterization of 1- (ethoxy (phenyl) methyl) -1H-benzo [ d ] [1,2,3] triazol (4 aha):
benzotriazol (0.6 mmol), benzaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4aha.
The product was characterized as:
yellow liquid(110.9mg,73％). 1 H NMR(400MHz,Chloroform-d)δ7.98-7.94(m,1H),7.35-7.32(m,2H),7.25-7.18(m,6H),7.11(s,1H),3.69-3.61(m,1H),3.40-3.33(m,1H),1.14(t,J＝7.0,3H). 13 C NMR(100MHz,Chloroform-d)δ147.00,136.40,131.10,129.02,128.59,127.46,125.96,124.22,119.91,111.69,89.55,77.48,76.84,65.01,14.73.HRMS(m/z)[ESI]:calculated for C 15 H 15 NNaO + m/z[M+Na] + :276.1107,found 276.1104。
example 12:
preparation and characterization of 1- (1-ethoxy-4- (4-methylpent-3-en-1-yl) cyclohex-3-en) -1H-benzo [ d ] [1,2,3] triazol (4 aia):
benzotriazol (0.6 mmol), 4- (4-methylpent-3-en-1-yl) cyclohex-3-en-1-al (2.4 mmol), tetrabutylammonium hexafluorophosphate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4aia.
The product was characterized as:
yellow liquid(121.2mg,75％).dr 1:1.3,as an inseparable diastereomeric mixture. 1 H NMR(400MHz,DMSO-d 6 )δ8.12-8.06(m,1H),7.96-7.94(m,1H),7.60-7.54(m,1H),7.47-7.41(m,1H),6.34-6.31(m,1H),6.22-6.20(m,0.43H),5.82-5.80(m,0.57H),5.33(dd,J＝11.8,10.2,1H),3.45-3.38(m,1H),3.20-3.07(m,2H),2.87(d,J＝4.4,0.51H),2.73(s,0.43H),2.08(ddd,J＝12.5,9.0,3.8,0.51H),1.84(s,0.57H),1.41-1.19(m,3H),1.08-0.95(m,4H). 13 C NMR(100MHz,DMSO-d 6 )δ145.84,145.76,138.53,138.42,132.15,131.71,131.66,131.41,127.83,127.76,124.37,119.55,119.49,111.36,111.34,93.44,92.97,64.02,63.74,48.89,48.68,44.09,43.25,43.19,42.75,42.10,41.69,29.99,27.50,14.58.HRMS(m/z)[ESI]:calculated for C 16 H 19 N 3 NaO + m/z[M+Na] + :292.1420,found 292.1422。
example 13:
preparation and characterization of 1- (1-ethoxy-3, 7-dimethyl-6-en-1-yl) -1H-benzo [ d ] [1,2,3] triazol (4 aja):
benzotriazol (0.6 mmol), citronellal (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4aja.
The product was characterized as:
yellow liquid(126.1mg,70％).dr 1.1:1,as an inseparable diastereomeric mixture. 1 H NMR(500MHz,Chloroform-d)δ8.06(d,J＝8.3,1H),7.77(d,J＝8.1,1H),7.47-7.44(m,1H),7.38-7.35(m,1H),6.16-6.13(m,1H),5.05(t,J＝7.0,52H),4.91(t,J＝7.0,0.48H),3.54-3.46(m,1H),3.29-3.21(m,1H),2.35-2.29(m,1H),2.22-2.17(m,1H),2.06-1.80(m,2H),1.65-1.57(m,5H),1.48-1.39(m,2H),1.32-1.18(m,2H),1.12(t,J＝7.0,3H),0.99(d,J＝6.4,1.52H),0.89(d,J＝6.7,1.48H). 13 C NMR(126MHz,Chloroform-d)δ146.92,146.90,131.64,131.62,131.44,131.33,127.46,127.43,124.40,124.25,124.22,124.17,120.17,111.41,111.36,89.65,89.45,64.61,41.79,41.43,36.90,36.86,28.92,28.78,25.80,25.70,25.29,25.18,19.66,19.22,17.77,17.67,14.84,14.82.HRMS(m/z)[ESI]:calculated for C 12 H 16 N 3 O + m/z[M+H] + :218.1288,found 218.1280。
example 14:
preparation and characterization of 1- (3- (4- (tert-butyl) phenyl) -1-ethoxy-2-methylpropyl) -1H-benzo [ d ] [1,2,3] triazol (4 aka):
benzotriazol (0.6 mmol), convaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aka.
The product was characterized as:
yellow liquid(151.8mg,72％).dr 1:1,as an inseparable diastereomeric mixture. 1 H NMR(500MHz,DMSO-d 6 )δ8.10-8.06(m,1H),7.94(dd,J＝12.1,8.4,1H),7.56(t,J＝8.2,1H),7.45-7.41(m,1H),7.31(d,J＝8.3,1H),7.18-7.15(m,2H),6.87(d,J＝8.2,1H),5.94(d,J＝8.0,0.51H),5.90(d,J＝8.0,0.49H),3.55-3.45(m,1H),3.20-3.15(m,1H),2.74-2.66(m,1H),2.28-2.23(m,0.5H),2.18-2.14(m,0.5H),1.26-1.19(m,10H),1.08-1.04m,3H),1.00(d,J＝6.6,2H),0.38(d,J＝6.8,1H). 13 C NMR(126MHz,DMSO-d 6 )δ148.28,148.15,145.71,145.66,136.19,135.84,132.01,131.79,128.90,128.36,127.79,127.75,125.05,124.89,124.38,124.29,119.50,119.46,111.46,92.99,92.83,64.35,64.28,37.57,36.97,34.08,33.99,31.20,31.13,15.25,14.56,13.93.HRMS(m/z)[ESI]:calculated for C 13 H 20 N 3 O + m/z[M+H] + :234.1601,found234.1617。
example 15:
preparation and characterization of 1- (benzo [ d ] [1,3] dioxo-4- (ethoxy) methyl) -1H-benzo [ d ] [1,2,3] triazol (4 ala):
benzotriazol (0.6 mmol), 1, 3-benzodioxo-4-carbaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, and the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4ala.
The product was characterized as:
yellow liquid(110.6mg,62％). 1 H NMR(400MHz,DMSO-d 6 )δ8.08(dd,J＝8.3,1.1,1H),
7.59(dt,J＝8.4,1.1,1H),7.49(ddd,J＝8.2,6.9,1.1,1H),7.43-7.37(m,2H),7.27(dd,J＝5.2,4.1,1H),6.97-6.96(m,2H),5.90(d,J＝0.9,1H),5.79(d,J＝0.9,1H),3.80-3.72(m,1H),3.42-3.37(m,1H),1.13(t,J＝7.0,3H). 13 C NMR(100MHz,DMSO-d 6 )δ147.45,145.71,144.28,131.42,127.89,124.39,121.67,119.58,119.04,118.18,110.93,109.27,101.37,84.30,64.44,14.59.HRMS(m/z)[ESI]:calculated for C 16 H 16 N 3 O 3 + m/z[M+H] + :298.1186,found 298.1190。
example 16:
preparation and characterization of 1- (1-methoxy-3-phenylpropyl) -1H-benzo [ d ] [1,2,3] triazole (4 aab):
benzotriazol (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium hexafluorophosphate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of methanol solvent for dissolution, using platinum sheets (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aab.
The product was characterized as:
yellow liquid(115.5mg,72％) 1 H NMR(500MHz,DMSO-d 6 )δ8.10(dt,J＝8.4,1.0,1H),
7.94(dt,J＝8.4,1.0,1H),7.58-7.56(m,1H),7.47-7.44(m,1H),7.27-7.24(m,2H),7.19-7.15(m,3H),6.04(t,J＝6.5,1H),3.14(s,3H),2.67-2.57(m,2H),2.48-2.42(m,2H). 13 C NMR(126MHz,DMSO-d 6 )δ＝145.77,140.28,131.69,128.42,128.27,127.88,126.09,124.45,119.56,111.26,89.92,55.91,35.25,30.45.HRMS(m/z)[ESI]:calculated for C 16 H 18 N 3 O + m/z[M+H] + :268.1444,found 268.1445。
example 17:
preparation and characterization of 1- (1-isopropoxy-3-phenylpropyl) -1H-benzo [ d ] [1,2,3] triazole (4 aac):
benzotriazol (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of isopropanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 2 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aac.
The product was characterized as:
yellow liquid(124.1mg,70％). 1 H NMR(400MHz,Chloroform-d)δ8.07(d,J＝8.3,1H),
7.80(d,J＝8.3,1H),7.49-7.45(m,1H),7.40-7.35(m,1H),7.28-7.24(m,2H),7.20-7.14(m,3H),6.18-6.15(m,1H),3.58-3.48(m,1H),2.81-2.72(m,1H),2.63-2.53(m,2H),2.42-2.34(m,1H),1.22(d,J＝6.1,3H),0.92(d,J＝6.2,3H). 13 C NMR(100MHz,Chloroform-d)δ146.93,140.19,131.41,128.60,128.46,127.42,126.33,124.28,120.13,111.60,87.93,77.48,76.84,70.46,36.61,31.17,22.78,21.21.HRMS(m/z)[ESI]:calculated for C 15 H 15 N 3 NaO + m/z[M+Na] + :276.1107,found 276.1109。
example 18:
preparation and characterization of 1- (1-tert-butoxy-3-phenylpropyl) -1H-benzo [ d ] [1,2,3] triazole (4 aad):
benzotriazol (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of tertiary butanol solvent for dissolution, using platinum sheets (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aad.
The product was characterized as:
yellow liquid(126.2mg,68％). 1 H NMR(400MHz,DMSO-d 6 )δ8.06(dt,J＝8.4,1.0,1H),
7.94(dd,J＝8.3,1.1,1H),7.57-7.53(m,1H),7.43-7.39(m,1H),7.26-7.22(m,2H),7.17-7.14(m,3H),6.41(t,J＝6.5,1H),2.72-2.64(m,1H),2.46-2.40(m,2H),2.32-2.24(m,1H),1.00(s,9H). 13 C NMR(101MHz,DMSO-d 6 )δ145.88,140.37,131.12,128.35,128.19,127.43,125.99,124.14,119.40,111.92,83.57,75.96,37.29,30.46,27.47.HRMS(m/z)[ESI]:calculated for C 18 H 28 N 3 O + m/z[M+H] + :302.2227,found 302.2229。
example 19:
preparation and characterization of 1- (1-n-pentyloxy-3-phenylpropyl) -1H-benzo [ d ] [1,2,3] triazole (4 aae):
benzotriazol (0.6 mmol), phenylpropionaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were each placed in a 10mL three-necked round bottom flask;
then adding 6.0mL of n-amyl alcohol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And purifying the residue by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aae.
The product was characterized as:
yellow liquid(137.8mg,71％). 1 H NMR(400MHz,Chloroform-d)δ8.08(d,J＝8.3,1H),
7.77(d,J＝8.4,1H),7.49-7.45(m,1H),7.40-7.36(m,1H),7.29-7.25(m,2H),7.20-7.14(m,3H),6.02(t,J＝6.6,1H),3.46-3.41(m,1H),3.22-3.16(m,1H),2.79-2.71(m,1H),2.65-2.58(m,2H),2.47-2.39(m,1H),1.54-1.48(m,2H),1.25-1.20(m,4H),0.84-0.79(m,3H). 13 CNMR(100MHz,Chloroform-d)δ146.87,140.15,131.41,128.61,128.49,127.50,126.35,124.31,120.16,111.32,90.13,77.48,76.84,69.25,36.24,31.13,28.95,28.14,22.34,13.98.HRMS(m/z)[ESI]:calculated for C 22 H 30 N 3 O + m/z[M+H] + :352.2383,found 352.2387。
example 20:
preparation and characterization of 1- (cyclohexyl (methoxy) methyl) -1H-benzo [ d ] [1,2,3] triazole (4 abb):
benzotriazol (0.6 mmol), cyclohexyl formaldehyde (2.4 mmol), tetrabutylammonium tetrafluoroborate (0.6 mmol) were placed in 10mL three-necked round bottom flasks, respectively;
then adding 6.0mL of methanol solvent for dissolution, using platinum sheets (1 cm x 1 cm) as an anode and a cathode, and stirring and reacting at the temperature of 60 ℃ under the protection of argon by using 12mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 3 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the desired product 4abb.
The product was characterized as:
yellow liquid(101.6mg,69％). 1 H NMR(400MHz,Chloroform-d)δ8.07(dt,J＝8.3,1.0,
1H),7.74(dt,J＝8.3,1.0,1H),7.48-7.44(m,1H),7.40-7.35(m,1H),5.60(d,J＝8.7,1H),3.23(s,3H),2.25-2.14(m,2H),1.84-1.78(m,1H),1.65-1.57(m,2H),1.26-1.03(m,6H),0.97-0.88(m,2H). 13 C NMR(100MHz,Chloroform-d)δ146.84,131.61,127.53,124.30,120.17,111.49,96.79,57.08,42.12,29.40,27.95,26.12,25.51,25.41.HRMS(m/z)[ESI]:calculated for C 14 H 20 N 3 O + m/z[M+H] + :246.1601,found 246.1607。
example 21:
amplification experimental preparation procedure of 1- (cyclohexyl (ethoxy) methyl) -1H-benzo [ d ] [1,2,3] triazole (4 aba):
benzotriazol (12 mmol), cyclohexyl formaldehyde (48 mmol), tetrabutyl ammonium tetrafluoroborate (24 mmol) were placed in a 350mL single-chamber cell, respectively;
then adding 120mL of ethanol solvent for dissolution, using a platinum sheet (1 cm x 1 cm) as an anode and a cathode, and stirring at 60 ℃ with 120mA constant current until the substrate is completely consumed (monitored by thin layer chromatography, the reaction time is 8 hours);
after the reaction was completed, it was directly concentrated under reduced pressure. And the residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether/ethyl acetate=15:1 elution) to give the target product 4aba (2.18 g, 70%).
The above examples demonstrate the synthesis of N- (α -alkoxyalkyl) azole compounds by the reaction of three components, oxazole, aldehyde and alcohol, under mild electrochemical conditions. The synthesis method avoids the use of an acid catalyst and an additional oxidation-reduction agent, and has the characteristics of mild reaction conditions, simplicity in operation, low production cost, high controllability and the like. Further, further enlargement research using gram-scale electrochemical reactor has shown that it is suitable for large-scale industrial production.
Claims (3)
1. Electrochemical synthesisN-(α-alkoxyalkyl) azole compounds, characterized in that said compounds have the following general formula:
；
in the general formula，R 1 An alkyl group; r is R 2 Alkyl, aryl; r is R 3 An alkyl group;
the aldehyde is aliphatic aldehyde and aromatic aldehyde; the alcohol is chain alcohol;
the electrolyte is as follows: tetrabutylammonium tetrafluoroborate or tetrabutylammonium hexafluorophosphate;
the solvent is as follows: methanol, ethanol, isopropanol, t-butanol or n-pentanol.
2. Electrochemical synthesis according to claim 1N-(α-alkoxyalkyl) azole compounds, characterized in that: the synthesis method comprises the following steps:
0.6mmol of benzotriazole, 2.4mmol of aliphatic aldehyde and aromatic aldehyde, and 0.6mmol of electrolyte were added to a 10mL three-necked round bottom flask, respectively;
adding 6.0mL of chain alcohol for dissolution, wherein the alcohol is a reaction substrate and also serves as a solvent, using platinum sheets as an anode and a cathode after dissolution, stirring and reacting at the temperature of 60 ℃ under argon and with a constant current of 12mA, and monitoring the reaction progress by adopting thin layer chromatography until the substrate is completely consumed;
after the reaction is completed, the mixture is directly concentrated under reduced pressure, and the concentrated solution is purified by 300-400 mesh silica gel column chromatography to obtain the target product.
3. Electrochemical synthesis according to claim 2N-(α-alkoxyalkyl) azole compounds, characterized in that: the column chromatography purification adopts petroleum ether/ethyl acetate as an eluent, wherein the volume ratio of petroleum ether/ethyl acetate is 15:1.
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