CN1256330C - Process for synthesizing benzimidazolone and its derivatives - Google Patents
Process for synthesizing benzimidazolone and its derivatives Download PDFInfo
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- CN1256330C CN1256330C CN 01113966 CN01113966A CN1256330C CN 1256330 C CN1256330 C CN 1256330C CN 01113966 CN01113966 CN 01113966 CN 01113966 A CN01113966 A CN 01113966A CN 1256330 C CN1256330 C CN 1256330C
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Abstract
The present invention relates to a synthetic method of benzimidazolone and a derivative. O-nitroaniline or o-nitroaniline compounds with substituent groups on benzene rings as substrates are dissolved in an autoclave containing inert solvent in the mode of selenium as a catalyst and tertiary amine as a cocatalyst, sealed, filled with a carbonylation agent with pressure of 0.1 to 6.0MPa and rapidly heated to 110 DEG C to 170 DEG C, and a finished product is prepared by refrigeration, residual gas discharge, filtration, drying and recrystallization after reaction for 1 to 10 hours under heat insulation. The present invention has the advantages of simple operation, low cost, high product yield and high purity.
Description
The present invention relates to the synthetic method of benzimidazolone and derivative thereof.
Benzimidazolone derivatives is the broad-spectrum fine chemicals of a class, can be used as the important as precursors of pigment, resin, contains in the molecular structure that (peptide bond CONH-), so most of biologically active, some also has pharmacologically active.The synthetic of benzimidazolone derivatives generally is to adopt the isocyanic ester original position intramolecularly amination that obtains by Hoffman, Curtius or Lossen rearrangement to generate; Perhaps adopt phosgene or do the carbonylation reaction that carbonylation agent carries out diamines based on the material of phosgene.In addition, also useful metal complex such as Mn
2(CO)
10, Ni (CO)
4, W (CO)
6Form benzimidazolone derivatives Deng doing the carbonylation that catalyzer carries out amine.Along with C
1The deep development of chemistry, people do the research interest of catalyzed carbonylation reaction of carbonylation agent to CO more and more denseer, it is catalyzer that the Yang Ying of the SONODA of Japan, China etc. has adopted per capita with selenium, with the diamine compound is substrate, with the carbon monoxide is the method for carbonylation agent, carry out carbonylation reaction, close the ring urea that ring has obtained a series of benzimidazolone derivatives or other type; The people such as Zhang Shanyan of China make catalyzer with selenium in the time of 100 ℃, adopt unsubstituted o-Nitraniline to do substrate, obtained benzimidazolone, but yield have only reached 43.3%; People such as the M.Vendelin of Slovakia then adopt alum thing, sulphur or low molecule sulfide and alkali to do catalyst system, in 80-250 ℃, under the 1-30MPa 2-N-methyl-p-nitroaniline that replaces is carried out carbonylation reaction, can obtain the target product benzimidazolone derivatives, but the difficult processing of sulfide.
The object of the present invention is to provide that a kind of operation is simpler, more economical, yield is high, purity good, Atom economy is high and the synthetic method of eco-friendly benzimidazolone and derivative thereof.
Technical scheme of the present invention is: make catalyzer with selenium, tertiary amine is made promotor, adopts inert solvent, to have the compound of substituent ortho-nitrophenyl amine on o-Nitraniline or the phenyl ring as substrate, be dissolved in the autoclave that fills inert solvent, sealing charges into carbonylation agent, its pressure is 0.1～6.0MPa, be warming up to 110 ℃～170 ℃ then rapidly, insulation reaction was down cooled off after 1～10 hour, bleed off residual gas, after filtration, behind dry, the recrystallization finished product; The equation of its reaction is:
R is various electronics or the electrophilic substituting groups given in the general formula;
Described selenium catalytic amount be have on described o-Nitraniline or the phenyl ring substituent ortho-nitrophenyl amine the compound molar weight 0.1～10%; Having the compound of substituent ortho-nitrophenyl amine and the input molar ratio of tertiary amine on described o-Nitraniline or the phenyl ring is 1: 1; Described tertiary amine is triethylamine, tributylamine etc., and consumption is chemical consumption; Described carbonylation agent is a CO (carbon monoxide converter) gas; Described inert solvent is toluene, acetone, tetrahydrofuran (THF) etc.; Reacting coarse product adopts methyl alcohol, ethanol, sherwood oil as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carries out the recrystallization purification.
The present invention has following advantage:
The present invention has used selenium to make catalyzer, with ortho-nitrophenyl aminated compounds cheap and easy to get is substrate, the reaction conditions gentleness, reaction yield and selectivity are better, Atom economy height and environmental friendliness, its purity almost reaches 100%, yield reaches 99.3%, and the aftertreatment ratio of product is easier to, and production technique is simple, operation is row easily, and cost is low.
Below by embodiment in detail the present invention is described in detail.
At volume is the o-Nitraniline (R represents hydrogen in the general formula) that adds 10mmol in 70 milliliters the stainless steel autoclave, 0.5mmol selenium powder, the triethylamine of 10mmol and 10g toluene, sealing, charge into carbon monoxide 3.0Mpa, put into oil bath, be warming up to 150 ℃ rapidly, insulation is reaction 4h down, be cooled to room temperature, open still, will filter the solid of gained and the solid merging that mother liquor concentrates gained, drying, weigh the product benzimidazolone, reacting coarse product adopts methyl alcohol as solvent, and with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, its amount is 15～25 to restrain, present embodiment is specially 15 grams, carries out recrystallization and purifies.Purity is almost 100%, and yield is 92.1%.
Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
Selenium of the present invention is made catalyzer, and triethylamine is done promotor, and toluene is made solvent, and temperature is high more, and the reaction times is long more, and carbon monoxide pressure is high more, and the product yield that obtains is then high more.Because the selectivity of reaction is good, so product is impure less.
Embodiment 2
At volume is the 3-methyl-2-N-methyl-p-nitroaniline (R is the substituting group to electronics in the general formula) that adds 10mmol in 70 milliliters the stainless steel autoclave, 0.5mmol selenium powder, the triethylamine of 10mmol and 10g toluene, sealing, charge into carbon monoxide 3.0Mpa, put into oil bath, be warming up to 150 ℃ rapidly, insulation is reaction 4h down, is cooled to room temperature, opens still, the solid of gained and the solid merging that mother liquor concentrates gained will be filtered, drying, weigh product 4-methyl-2-benzimidazolone, reacting coarse product adopts ethanol as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carry out recrystallization and purify.Purity is almost 100%, and yield is 99.3%.
Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
Embodiment 3
At volume is to add 2 of 10mmol in 70 milliliters the stainless steel autoclave, the 4-dinitraniline, 0.5mmol selenium powder, triethylamine and the 10g toluene of 10mmol, sealing, charge into carbon monoxide 3.0Mpa, put into oil bath, be warming up to 150 ℃ rapidly, insulation is reaction 4h down, is cooled to room temperature, open still, to filter the solid of gained and the solid merging that mother liquor concentrates gained, drying, reacting coarse product adopts sherwood oil as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carry out recrystallization and purify.Weigh product 5-nitro-2-benzimidazolone, purity is almost 100%, yield is 91.6%.
Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
Embodiment 4
At volume is to add 2 of 10mmol in 70 milliliters the stainless steel autoclave, the 4-dinitraniline, 0.5mmol selenium powder, the triethylamine of 10mmol and 10g toluene, sealing charges into carbon monoxide 3.0Mpa, puts into oil bath, be warming up to 130 ℃ rapidly, insulation is reaction 4h down, is cooled to room temperature, opens still, the solid of gained and the solid merging that mother liquor concentrates gained will be filtered, drying, reacting coarse product adopt methyl alcohol as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carrying out recrystallization purifies, weigh product 5-nitro-2-benzimidazolone, purity is almost 100%, yield is 91.1%.
Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
Embodiment 5
At volume is the 4-chloro-2-N-methyl-p-nitroaniline that adds 10mmol in 70 milliliters the stainless steel autoclave, 0.5mmol selenium powder, the triethylamine of 10mmol and 10g toluene, sealing, charge into carbon monoxide 3.0Mpa, put into oil bath, be warming up to 140 ℃ rapidly, insulation is reaction 4h down, is cooled to room temperature, open still, to filter the solid of gained and the solid merging that mother liquor concentrates gained, drying, reacting coarse product adopts methyl alcohol as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carry out recrystallization and purify, weigh product 5-chloro-2-benzimidazolone, yield is 65.9%.
Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
Embodiment 6
At volume is the 4-methyl-2-N-methyl-p-nitroaniline that adds 10mmol in 70 milliliters the stainless steel autoclave, 0.5mmol selenium powder, the triethylamine of 10mmol and 10g toluene, sealing, charge into carbon monoxide 3.0Mpa, put into oil bath, be warming up to 160 ℃ rapidly, insulation is reaction 10h down, is cooled to room temperature, open still, to filter the solid of gained and the solid merging that mother liquor concentrates gained, drying, reacting coarse product adopts methyl alcohol as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carry out recrystallization and purify, weigh product 5-methyl-2-benzimidazolone, yield is 68.9%.Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
Embodiment 7
At volume is the 5-chloro-2 that adds 10mmol in 70 milliliters the stainless steel autoclave, the 4-dinitraniline, the selenium powder of 1mmol, the triethylamine of 10mmol and 10g tetrahydrofuran (THF), sealing, charge into carbon monoxide 3.0Mpa, put into oil bath, be warming up to 110 ℃ rapidly, insulation is reaction 7h down, be cooled to room temperature, open still, will filter the solid of gained and the solid merging that mother liquor concentrates gained, dry, reacting coarse product adopts methyl alcohol as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carries out the recrystallization purification, weigh product 6-chloro-5-nitro-2-benzimidazolone, yield is 50.1%.
Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
Embodiment 8
At volume is the 5-bromo-2 that adds l0mmol in 70 milliliters the stainless steel autoclave, the 4-dinitraniline, 0.2mmol selenium powder, the tributylamine of 10mmol and 10g acetone, sealing, charge into carbon monoxide 3.0Mpa, put into oil bath, be warming up to 170 ℃ rapidly, insulation is reaction 1h down, be cooled to room temperature, open still, will filter the solid of gained and the solid merging that mother liquor concentrates gained, dry, reacting coarse product adopts methyl alcohol as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carries out the recrystallization purification, weigh product 6-bromo-5-nitro-2-benzimidazolone, yield is 64.7%.
Assay adopts highly effective liquid phase chromatographic system, do moving phase with methyl alcohol, tetrahydrofuran (THF), water, flow velocity 0.8ml/min, (DIDL 10 μ l 250 * 4mm) are chromatographic column with LiChrosorb, with ELSD is detector, and 70 ℃ of drift tube temperatures, gas flow are 1.605LPM, sample size is 2 μ l, and the peak area external standard method is quantitative.
R substituting group of the present invention removes above-mentioned each exception of mentioning, and other gives electronics or electrophilic substituting group also within design philosophy scope of the present invention; Described tertiary amine except that the above-mentioned triethylamine of mentioning, tributylamine, other tertiary amine also be the technology of the present invention thought in one's power; The present invention can also adopt other inert solvent.
Claims (6)
1. the synthetic method of benzimidazolone and derivative thereof, make catalyzer with selenium, tertiary amine is made promotor, adopt inert solvent, to have the compound of substituent ortho-nitrophenyl amine on o-Nitraniline or the phenyl ring as substrate, be dissolved in the autoclave that fills inert solvent, sealing, the equation of its reaction is:
R is various electronics or the electrophilic substituting groups given in the general formula;
Charge into CO, its pressure is 0.1～6.0MFa, it is characterized in that: after charging into CO, be warming up to 110 ℃～170 ℃ rapidly, down reaction is after 1～10 hour in insulation, and cooling bleeds off residual gas, after filtration, behind dry, the recrystallization finished product.
2. according to the described synthetic method of claim 1, it is characterized in that: described selenium catalytic amount be have on described o-Nitraniline or the phenyl ring substituent ortho-nitrophenyl amine the compound molar weight 0.1～10%.
3. according to the described synthetic method of claim 1, it is characterized in that: having the compound of substituent ortho-nitrophenyl amine and the input molar ratio of tertiary amine on described o-Nitraniline or the phenyl ring is 1: 1.
4. according to the described synthetic method of claim 1, it is characterized in that: described tertiary amine is triethylamine, tributylamine.
5. according to the described synthetic method of claim 1, it is characterized in that: described inert solvent is toluene, acetone, tetrahydrofuran (THF).
6. according to the described synthetic method of claim 1, it is characterized in that: reacting coarse product adopts methyl alcohol, ethanol, sherwood oil as solvent, with the addition of reacting coarse product when described solvent dissolves during near boiling temperature fully, carries out the recrystallization purification.
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| CN 01113966 CN1256330C (en) | 2001-05-18 | 2001-05-18 | Process for synthesizing benzimidazolone and its derivatives |
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| CN 01113966 CN1256330C (en) | 2001-05-18 | 2001-05-18 | Process for synthesizing benzimidazolone and its derivatives |
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| CN1256330C true CN1256330C (en) | 2006-05-17 |
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