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CAS No. : | 598-55-0 | MDL No. : | MFCD00007964 |
Formula : | C2H5NO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GTCAXTIRRLKXRU-UHFFFAOYSA-N |
M.W : | 75.07 | Pubchem ID : | 11722 |
Synonyms : |
|
Num. heavy atoms : | 5 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.5 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 16.11 |
TPSA : | 52.32 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.23 cm/s |
Log Po/w (iLOGP) : | 0.91 |
Log Po/w (XLOGP3) : | -0.66 |
Log Po/w (WLOGP) : | -0.29 |
Log Po/w (MLOGP) : | -0.96 |
Log Po/w (SILICOS-IT) : | -0.9 |
Consensus Log Po/w : | -0.38 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | 0.18 |
Solubility : | 113.0 mg/ml ; 1.5 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 0.03 |
Solubility : | 81.4 mg/ml ; 1.08 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | 0.53 |
Solubility : | 257.0 mg/ml ; 3.42 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.18 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P201-P202-P264-P280-P305+P351+P338-P312-P337+P313-P405-P501 | UN#: | N/A |
Hazard Statements: | H302+H312-H319-H351 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | at 145 - 150℃; for 10 h; | Example 1 :; 50 g (0.2564 mol) of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol was reacted at 145°C- 1500C for 10 hours with 25.0 g (0.333 mol) of methyl carbamate in the presence of 0.005- 0.006 mol of base (LiNH2, methanolic solution of NaOCH3, NaOH, or KOH). The completion of the reaction is checked by HPLC. The hot reaction mixture was treated with 100 mL of water and 150 mL of butyl acetate. The pH of the mixture was adjusted to 5 with acetic acid. Two layers were separated at 80°C-90°C. The residual water in the organic layer is separated by distillation. Upon cooling, the organic phase separated metaxalone crude at 70percent-72percent yield. The crude metaxalone is purified by crystallization from a carbon treated butyl acetate solution. Yield: 92percent-95percentFurther experiments concerning the reaction parameters have shown that: a. the reaction time is solely a function of temperature; b. the amount of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol residual (unreacted) starting material is also a function of temperature; c. the concentration of the impurities is a function of both temperature and methyl carbamate stoichiometry, where lower temperatures and lower mole ratios of methyl carbamate to 3-(3,5-dimethylphenoxy)-l-amino-2-propanol minimize the impurities formation; and d. the yield is increased at lower mole ratios of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol and at higher temperatures. <n="5"/>In summary, the reaction should be run at the lower temperature in order to minimize the formation of impurities and lower molar ratio of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol is preferable. |
92% | at 145 - 150℃; for 10 h; | Example 1 :; 50 g (0.2564 mol) of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol was reacted at 145°C- 1500C for 10 hours with 25.0 g (0.333 mol) of methyl carbamate in the presence of 0.005- 0.006 mol of base (LiNH2, methanolic solution of NaOCH3, NaOH, or KOH). The completion of the reaction is checked by HPLC. The hot reaction mixture was treated with 100 mL of water and 150 mL of butyl acetate. The pH of the mixture was adjusted to 5 with acetic acid. Two layers were separated at 80°C-90°C. The residual water in the organic layer is separated by distillation. Upon cooling, the organic phase separated metaxalone crude at 70percent-72percent yield. The crude metaxalone is purified by crystallization from a carbon treated butyl acetate solution. Yield: 92percent-95percentFurther experiments concerning the reaction parameters have shown that: a. the reaction time is solely a function of temperature; b. the amount of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol residual (unreacted) starting material is also a function of temperature; c. the concentration of the impurities is a function of both temperature and methyl carbamate stoichiometry, where lower temperatures and lower mole ratios of methyl carbamate to 3-(3,5-dimethylphenoxy)-l-amino-2-propanol minimize the impurities formation; and d. the yield is increased at lower mole ratios of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol and at higher temperatures. <n="5"/>In summary, the reaction should be run at the lower temperature in order to minimize the formation of impurities and lower molar ratio of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol is preferable. |
91.3% | at 145 - 150℃; for 10 - 14 h; | Example 1 :; 50 g (0.2564 mol) of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol was reacted at 145°C- 1500C for 10 hours with 25.0 g (0.333 mol) of methyl carbamate in the presence of 0.005- 0.006 mol of base (LiNH2, methanolic solution of NaOCH3, NaOH, or KOH). The completion of the reaction is checked by HPLC. The hot reaction mixture was treated with 100 mL of water and 150 mL of butyl acetate. The pH of the mixture was adjusted to 5 with acetic acid. Two layers were separated at 80°C-90°C. The residual water in the organic layer is separated by distillation. Upon cooling, the organic phase separated metaxalone crude at 70percent-72percent yield. The crude metaxalone is purified by crystallization from a carbon treated butyl acetate solution. Yield: 92percent-95percentFurther experiments concerning the reaction parameters have shown that: a. the reaction time is solely a function of temperature; b. the amount of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol residual (unreacted) starting material is also a function of temperature; c. the concentration of the impurities is a function of both temperature and methyl carbamate stoichiometry, where lower temperatures and lower mole ratios of methyl carbamate to 3-(3,5-dimethylphenoxy)-l-amino-2-propanol minimize the impurities formation; and d. the yield is increased at lower mole ratios of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol and at higher temperatures. <n="5"/>In summary, the reaction should be run at the lower temperature in order to minimize the formation of impurities and lower molar ratio of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol is preferable.; Example 2:; The methyl carbamate stoichiometry is determinant for the formation of the major impurity. The limit of diminishing returns has been demonstrated to be at 1.25-1.35 equivalents of methyl carbamate. As shown in Table 1, the data also show that LiNH2 or CH3ONa can be used interchangeably. <n="6"/> <n="7"/>The 3-(3,5-dimethylphenoxy)-l-amino-2-propanol starting material has to be of good quality including chemical purity and color. Colored impurities are only partially removed by the butyl acetate treatment and impact the quality of the final product with respect to color. Accordingly, it is advantageous for carbon treatment to be applied either to the crude or to the final purification step.In addition, the filtrate from the final purification can be recycled in part. Unreacted 3-(3,5- dimethylphenoxy)-l-amino-2-propanol can be separated from the concentrated filtrates and can be recycled after separation by filtration and drying. A better alternative would be to run the reaction as close to completion as practical. |
90.7% | at 145 - 150℃; for 5.5 - 10 h; | Example 1 :; 50 g (0.2564 mol) of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol was reacted at 145°C- 1500C for 10 hours with 25.0 g (0.333 mol) of methyl carbamate in the presence of 0.005- 0.006 mol of base (LiNH2, methanolic solution of NaOCH3, NaOH, or KOH). The completion of the reaction is checked by HPLC. The hot reaction mixture was treated with 100 mL of water and 150 mL of butyl acetate. The pH of the mixture was adjusted to 5 with acetic acid. Two layers were separated at 80°C-90°C. The residual water in the organic layer is separated by distillation. Upon cooling, the organic phase separated metaxalone crude at 70percent-72percent yield. The crude metaxalone is purified by crystallization from a carbon treated butyl acetate solution. Yield: 92percent-95percentFurther experiments concerning the reaction parameters have shown that: a. the reaction time is solely a function of temperature; b. the amount of 3-(3,5-dimethylphenoxy)-l-amino-2-propanol residual (unreacted) starting material is also a function of temperature; c. the concentration of the impurities is a function of both temperature and methyl carbamate stoichiometry, where lower temperatures and lower mole ratios of methyl carbamate to 3-(3,5-dimethylphenoxy)-l-amino-2-propanol minimize the impurities formation; and d. the yield is increased at lower mole ratios of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol and at higher temperatures. <n="5"/>In summary, the reaction should be run at the lower temperature in order to minimize the formation of impurities and lower molar ratio of methyl carbamate to 3 -(3, 5- dimethylphenoxy)-l-amino-2-propanol is preferable.; Example 2:; The methyl carbamate stoichiometry is determinant for the formation of the major impurity. The limit of diminishing returns has been demonstrated to be at 1.25-1.35 equivalents of methyl carbamate. As shown in Table 1, the data also show that LiNH2 or CH3ONa can be used interchangeably. <n="6"/> <n="7"/>The 3-(3,5-dimethylphenoxy)-l-amino-2-propanol starting material has to be of good quality including chemical purity and color. Colored impurities are only partially removed by the butyl acetate treatment and impact the quality of the final product with respect to color. Accordingly, it is advantageous for carbon treatment to be applied either to the crude or to the final purification step.In addition, the filtrate from the final purification can be recycled in part. Unreacted 3-(3,5- dimethylphenoxy)-l-amino-2-propanol can be separated from the concentrated filtrates and can be recycled after separation by filtration and drying. A better alternative would be to run the reaction as close to completion as practical. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With triethylamine In methanol; dichloromethane; ethyl acetate | 3.3.i Method 3a(i) Method 3a(i) A solution of triethylamine (7.2 ml, 0.052 mol) and homoveratrylamnine (1.92ml, 0.011 mol) in dichloromethane (10 ml) was added to a solution of methyl chloroformate (8 ml, 0.103 mol) in dichloromethane (50 ml) and cooled to -78° C. The reaction mixture was warmed to room temperature and stirred for 18 hours. It was then poured onto saturated sodium carbonate solution, extracted into dichloromethane, dried over magnesium sulphate, and the solvent removed in vacuo to yield a yellow oil which was purified using flash chromatography (1% methanol in ethyl acetate) to yield the methyl carbamate (2.06 g, 78%). |
With ammonia; benzene | ||
With potassium hydrogencarbonate In water | 5 EXAMPLE 5 EXAMPLE 5 A 500 mL 3-neck round bottom flask was equipped with an overhead stirrer, temperature probe, and nitrogen line. The amino alcohol 3 (35.38 mmol, 10.25 g) and MTBE (100 mL) were charged, forming a light slurry. The water (100 mL) was charged, followed by potassium bicarbonate (2 equ, 7.08 g). Methyl chloroformate (2 equiv., 5.46 mL) was charged via syringe, and the biphasic mixture was stirred vigorously at 20-25° C. Samples were assayed by HPLC until <0.5% amino alcohol 3 remained (approximately 8.5 hours). The layers were separated, and the organic layer was washed with brine (100 mL) and dried over magnesium sulfate. After filtration, a solvent switch (50-60° C. under vacuum) was carried out into a MTBE--heptane mixture (approx. 5% MTBE by volume as measured by 1 H NMR) of 102 mL (10 mL/g starting material) total volume. The methyl carbamate 5 crystallized readily during the solvent switch. After aging the slurry at 20-25° C. for approx. 30 min, the material was filtered. The solid was washed with the mother liquors, and then with one cake volume of heptane. The dry methyl carbamate 5 was isolated in 92% yield (11.32 g). 1-2% was lost to the mother liquors. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.41% | With alumina supported titanium dioxide-bismuth oxide metal oxide catalyst at 120℃; for 8h; Sealed tube; | 1.B B. Preparation of methyl carbamate 420 g of urea, 3000 mL of methanol and 4.2 g of catalyst A are sequentially introduced into a 10 L reaction vessel, sealed, heated to 120° C. and reacted at this temperature for 8 hours to obtain methyl carbamate.After testing, the yield of methyl carbamate was 99.41%.No carbamate-like methyl ester was detected in benzyl carbamate (exceeding the detection limit of 0.00001%). |
98.9% | Stage #1: methanol; urea at 30℃; for 20h; Autoclave; Stage #2: With carbon dioxide; 6O4P(3-)*5Ni(2+)*5Ca(2+)*2F(1-) at 160℃; for 6h; | 1 A process for the preparation of methyl carbamate by urea alcoholysis (1)In a high-pressure autoclave with a magnetic stirrer and a heating and tempering system, methanol, urea, and the like were added to the reaction vessel of urea, urea, and the like. 30 ° C, stir for 20 min to make it fully mixed, then add the catalyst Ni5Ca5 (P04) 6F2, into the C02 three times, replace the kettle in the air, the reactor 2 pressure of 0.6 MPa, at a temperature of 160 ° The mass ratio of catalyst Ni5Ca5 (P04) 6F2 to the total mass ratio of urea and methanol was 4: 100, the molar ratio of methanol to urea was 15: 1; the specific amount was: 1.0 g of urea, 10 mL, the catalyst attached to Ni5Ca5 (PO4) 6F2 0.72 g(2) The reaction system was reduced to room temperature, the catalyst was removed by filtration, and methanol was distilled off to give the desired product methyl carbamate. |
98% | With silica supported titanium dioxide at 160℃; for 8h; Inert atmosphere; | 2-4 Example 4 A method for producing methyl carbamate, which is produced by using the equipment in Example 1, wherein the length of the outer tube 51 is 0.3 m, the length of the outer tube 52 is 0.15 m, the length of the outer tube 53 is 0.15 m, and the length of the outer tube 54 The length of the outer tube 55 is 0.05 m.The steps to produce urethane include:Step 1: First introduce 6000mL of methanol, 426 urea, and 21g of catalyst into the reactor in sequence, close the valve for releasing gas on the exhaust channel, and then flush 0.9MPa of inert gas into the reaction system; inert gas is nitrogen , The catalyst uses silica-supported titanium dioxide, the content of titanium dioxide is 2.9%;Step 2: The temperature of the exhaust passage is divided into 4 sections and 5 sections. The exhaust pipe section where the outer pipe 51 is located uses tap water for temperature control, that is, the outer pipe 51 is fed with 20 ° C tap water for temperature control, and the remaining sections of the exhaust passage are used for temperature control. The temperature is controlled by constant temperature circulating water. Specifically, the outer tube 52 is controlled by 20 ° C constant temperature circulating water, the outer tube 53 is controlled by 35 ° C constant temperature circulating water, and the outer tube 54 is controlled by 50 ° C. The temperature is controlled by water. The outer tube 55 is controlled by 65 constant temperature circulating water.Step 3: Increase the temperature in the reactor to 160 ° C, then open the gas cylinder and purge nitrogen, and then open the exhaust channel of the reactor to keep the pressure of the reaction system constant and maintain the pressure of the reaction system at 2.3Mpa (gauge pressure 2.3Mpa) The retention time is 8 hours (the reaction time is also 8 hours) to obtain methyl carbamate. |
With copper diacetate at 130℃; | ||
at 157.212 - 164.434℃; for 146h; | 3 A one liter stirred reactor (autoclave) with a distillation column was used to remove impurities in an 8.03 wt. % urea solution in methanol and convert urea to methyl carbamate. No catalyst was charged to the reactor. The experiment was carried out at 315° F. under 200 psig and 328° F. under 230 psig by pumping in the urea solution into the reactor at 4 ml/min with the constant bottom flow rate at 2 ml/min for 27 hours and 3 ml/min with the constant bottom flow rate at 1.5 ml/min to the end (146 hours on stream time) of the run. The distillation column is operated with overhead reflux. During the operation, the overhead flow was adjusted to maintain a constant liquid level (50% full) in the autoclave. The column operation was done with overhead reflux from the overhead reflux drum. The MC concentration in the bottom stream from the autoclave was about 20% on average, which corresponds to about 97% conversion of urea to MC. The urea feed contained about 2000 ppm water. The bottom products contained 375 ppm water at 315° F. and 300 ppm water at 328° F. on average. | |
at 180℃; for 6h; Sealed vessel; | 10 Example 10; 1000 ml methanol, 70 g urea and 7 g catalyst A or B or C, respectively, were successively added into a 2 L stainless steel reaction vessel equipped with a magnetic stirrer and a gas releasing valve. The reaction vessel was sealed and heated to 180° C., and then the reaction were proceeded for 6 hours, the reaction pressure was 2 MPa. During the reaction, ammonia gas formed during the reaction is released 3 times through the gas releasing valve. After 6 hours, the reaction was stopped and the reactor was, cooled to room temperature. The catalyst could be recovered from the resulting solution containing methanol and raw products by filtration. Raw methyl carbamate (MC) was obtained as a solid, when the solution containing methanol and raw products were distilled at 80° C. to remove methanol. The raw MC was dissolved in 80 ml diethyl ether and filtrated to remove the possible excess urea. The solution obtained from the filtration was evaporated at 60° C. to remove the diethyl ether. MC was obtained as a white solid with the purity being more than or equal to 98%. The results are shown in Table 1. | |
at 160℃; for 2h; Inert atmosphere; Autoclave; Green chemistry; | 5 EXAMPLE 5 Similar to EXAMPLE 1 except this reaction was carried out at 160°C with higher nitrogen flow. The HPLC and GC analysis of both reaction mixtures showed 97.4% conversion of urea and 98.8% selectivity to MC. Under above mentioned identical conditions when reaction was carried out without nitrogen sparging 88.7% conversion of urea and 91.1% selectivity to MC was observed. | |
With cenospheres at 180℃; for 8h; | 11 Example 11 Urea 7.5 g (120 mmol), methanol 64 g (2000 mmol) and 1 g of cenospheres were charged to a 300 ml reactor. The contents were heated to 180 °C with slow stirring. After attaining the temperature stirring speed was increased to 1000 rpm and the time was noted as zero time. The reaction was continued for .8 hours. Ammonia formed during the reaction was removed using cooled high pressure condenser (condenser was cooled to 15°C) fitted above the gas outlet valve of the reactor. Ammonia was removed at the interval of 1 hour during the course of the reaction. After 8 h reaction the reactor was cooled to 25°C. Reaction mixture was analyzed by Gas Chromatography and 93.6 % conversion of urea and 65.9 % selectivity to MC and ~ 1% selectivity to DMC was observed in the reaction | |
With samarium(III) nitrate at 180℃; for 2h; Inert atmosphere; | 14 Urea 25 g (416 mmol) and methanol 220 g (6875 mmol) with 1.2g of Sm(N03)3were charged to a 2000 ml reactor connected to a nitrogen reservoir from gas inlet valve. The reservoir is fitted to reactor through constant pressure regulator which is set at 400 psi. A back pressure regulator was fitted to reactor at gas outlet valve. Back pressure regulator is set at 390 psi. The pressure difference of 10 psi was maintained between constant pressure regulator and back pressure regulator to ensure positive flow of nitrogen. This will help in stripping of CH3OH along with NH3 that is formed during reaction. The reactor was then pressurized with nitrogen atmosphere at 400 psi and 25 ml methanol was added to the reactor prior to heating. The inlet valve was closed at this point keeping outlet valve open. The contents were heated to 180 °C under very slow stirring condition. After attaining the temperature the inlet valve was opened. The reaction was continued 2 h. During this period methanol along with NH3 was expelled due to the set positive pressure of nitrogen. This methanol along with dissolved NH3 was collected in a trap (cooled with ice and salt mixture) connected to BPR outlet. After completion of reaction the reactor was cooled to 25°C. Reaction mixture from bomb as well as from trap was analyzed by HPLC and Gas Chromatography. From HPLC analysis 100%) conversion of urea was observed. GC analysis showed 44%) selectivity towards MC, 3.08 %> selectivity for DMC and 1.7 % selectivity for MNMC. | |
With tin(IV) chloride at 140℃; | ||
With boron trifluoride | ||
With carbon dioxide; 6O4P(3-)*2F(1-)*5Ca(2+)*5Zn(2+) In neat (no solvent) at 140℃; for 3h; Autoclave; | The catalytic reaction for the synthesis of MC was conducted in a stainless-steel autoclave reactor system of 50 mL equipped with electric heating and stirring. In a typical operation, 1.0 g of urea, 10 mL of methanol and 0.05 g of catalyst were added to the reactor followed by a CO2 gas purge three times to displace the air in it. The reactor was then heated and maintained at 140 °C for 3 h using a 900 rpm stirring rate. After completion of reaction, the mixture was filtered to remove the catalyst, and the remaining solution was identified by GC-MS and analyzed by gas chromatography (Agilent GC6890-5973I) to determine quantitatively the composition of the products. | |
With tetrabutoxytitanium; bismuth(III) nitrate; nitric acid; silica gel at 150℃; for 4h; Sealed tube; | 1.A-1.B; 2.A-2.B; 3.A-3.B; Example 2The preparation of methyl carbamate is as follows A. Preparation of silica-supported titanium dioxide-bismuth oxide catalystDissolve 0.4 g of bismuth nitrate and 4 g of tetrabutyl titanate in 15 ml of a 2 mol / L nitric acid solution.After the solution was clarified, 13 g of silica was added to the above solution, and left at room temperature for 6 hours.Catalyst B was then dried at 120 ° C for 3h, and finally calcined at 600 ° C for 3h.B. Production of methyl carbamate71g of urea, 1000ml of methanol and 3.5g of catalyst B were sequentially introduced into a 2L reactor,Sealed, heated to 150 ° C, and reacted for 4 hours to obtain methyl carbamate. After testing,The yield of methyl carbamate was 99%,No urethane-like was detected in the urethane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.1% | In benzene; | EXAMPLE 9 Reaction of 3.29 g (0.01 mol) of <strong>[5293-83-4](hydroxymethyl)triphenylphosphonium chloride</strong> with 0.75 g (0.01 mol) of methyl carbamate, following Example 1 but using benzene instead of ethyl acetate, gave 2.82 g (73.1% yield) of (N-carbomethoxylaminomethyl)triphenylphosphonium chloride, (CH3 O2 CNHCH2)(C6 H5)3 P+ Cl-, as a white, crystalline solid, mp 198.5-199 C. d after recrystallization from 2-propanol. IR (Nujol) 688m, 697w, 720m, 736m, 752m, 774w, 841w, 994w (P-C6 H5), 1020m, 1110s, 1165w, 1190m, 1255vs, 1310m, 1430s (P-C6 H5), 1460m, 1540m (NH, amide II), 1580w (C=C), 1720vs (C=O, amide I), and 3170m,sh (NH) cm-1. 1 H NMR (DMSO-d6) delta 2.36 (s, 3H, CH3), 4.39 d pair, 2H, CH2, J=3.0 Hz, collapsing with D2 O to d, delta 4.31, JPCH =3.0 Hz), 6.87 (m, 15H, C6 H5; d at delta 6.92, J=2.0 Hz collapsing with D2 O to s, delta 6.90) and 7.67 (m, IH, NH, vanishing with D2 O). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In diethyl ether | 2.A Example 2: Part A: Glyoxylic acid monohydrate (20.0 g, 218 mmol) and methyl carbamate (16.3 g, 218 mmol) were dissolved in diethyl ether (200 ml_) and stirred overnight. The solids were filtered to provide the desired product 7 (32.0 g, 98%). |
98% | In diethyl ether | |
98% | With water In diethyl ether | 400.A Part A: Glyoxylic acid monohydrate (20.0 g, 218 mmol) and methyl carbamate (16.3 g, 218 mmol) were dissolved in diethyl ether (200 ml) and stirred overnight. The solids were filtered to provide the desired product 306B (32.0 g, 98%). |
98% | In diethyl ether | 2.A Part A: Glyoxylic acid monohydrate (20.0 g, 218 mmol) and methyl carbamate (16.3 g, 218 mmol) were dissolved indiethyl ether (200 mL) and stirred overnight. The solids were filtered to provide the desired product 7 (32.0 g, 98%). |
93% | In diethyl ether at 24℃; for 12h; | |
In diethyl ether at 20℃; | Scheme S2: Methods for attempts at the synthesis of cpGlu using an akynyl glycine synthon. Compounds S2, S3, 2a and 3a A solution of methyl carbamate (6.76 g, 90.05 mmol, 1 eq) and glyoxylic acid (6.67 g, 90.05 mmol, 1 eq) in Et2O (75 mL) was stirred at rt overnight. The white solid that formed in the reaction mixture was filtered and washed with ice cold Et2O (100 mL). The product was slightly soluble in Et2O, so the filtrate was concentrated to half the volume and filtered again to recover the desired product. The combined solids were dried under reduced pressure to obtain a white powder S2 (13.00 g, 96.8%) that was used without further purification. Rf = 0.35 (50% DCM/MeOH, visualized w/ CAM stain). 1H NMR (500 MHz, CD3OD): δ = 5.39 (s, 1H), 3.68 (s, 3H). 13C NMR (125 MHz, CD3OD): δ = 172.66, 158.57, 74.54, 52.73. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: methyl carbamate With thionyl chloride In diethyl ether at 0 - 20℃; for 0.583333h; Inert atmosphere; Stage #2: With pyridine In diethyl ether at 20℃; for 3h; Inert atmosphere; | 4.2. Procedure for the synthesis of compound 10 To a solution of methyl carbamate (20.0 g, 266 mmol) in diethyl ether (300 ml) was added SOCl2 (21.0 mL, 288 mmol) at 0 °C, after stirring for 5 min the reaction mixture was allowed to warm to rt and stirred for a further 30 min. A solution of pyridine (40.9 mL, 506 mmol) in diethyl ether (60.0 mL) was added slowly over 1.5 h and then stirred for further 1.5 h. The resulting precipitate was filtered under N2. The filtrate was concentrated in vacuo to give 9 (32.0 g, 264 mmol, Quant.) as yellow oil. The material was used without any further purification [1H NMR (400 MHz, CDCl3) δ 3.94 (3H, s, CH3)]. To a solution of methyl N-(sulfinylidene)carbamate (9, 10.0 g, 83 mmol) in benzene (60.0 mL) was added freshly distilled cyclopentadiene (9.7 mL, 116 mmol) dropwise and the resulting solution was stirred for 20 h at rt. The solution was diluted with THF (110 mL) and phenylmagnesium bromide (1 M in THF, 83.0 mL, 83 mmol) was added over 45 min then stirred for 30 min before being quenched by addition of satd aq NH4Cl (100 mL). Extracted with EtOAc (3 × 100 mL), combined organic phases were washed with brine (100 mL), dried (MgSO4) and concentrated in vacuo. Purification (MPLC, Si, EtOAc/petrol, 80%) gave 10 as mixture of diastereomers in approx. 85% purity, which was used in the subsequent reaction (10.4 g, thick oil, estimated 48% yield taking into account small impurities). 4.2.1 Compound 1012b Orange coloured oil. Rf = 0.72 (EtOAc); IR cm-1 3011, 2360, 2341, 1716, 1516; 1H NMR (400 MHz, CDCl3) δ 7.57-7.47 (5H, m, H-Ar), 6.17-5.99 (2H, m, H-2 and H-3), 5.83 (1H, d, J = 8.8 Hz, NH), 4.78 (1H, dd, J = 8.8 and 8.7 Hz, H-1), 3.84-3.78 (1H, m, H-4), 3.68 (3H, s, CH3), 2.17 (1H, ddd, J = 15.3, 8.7 and 8.5 Hz, H-5), 1.78-1.73 (1H, m, H-5); 13C NMR (100 MHz, CDCl3) 171.1 (CO2Me), 156.3 (C-Ar), 142.0 (C-2 or C-3), 130.9 (C-Ar), 129.3 (C-Ar), 129.1 (C-Ar), 128.0 (C-2 or C-3), 124.0 (C-Ar), 71.2 (C-4), 53.4 (C-1), 52.0 (CH3), 29.2 (C-5); HRMS ESI+ m/z C13H15NO3S calculated: 288.0665 [M+Na]+, found: 288.0654 |
76% | With pyridine; thionyl chloride In diethyl ether at 0 - 25℃; for 3h; | |
With pyridine; thionyl chloride | 1 EXAMPLE 1 EXAMPLE 1 Amination of 2-Methyl-2-butene. Pyridine (65.0 g, 0.823 momol) was added in drops during a period of 0.5 h to a solution of methyl carbamate (30.0 g, 0.400 mol) and SOCl2 (47.6 g, 0.400 mol) in 500 mL of ether that was cooled in an ice bath and stirred. The bath was removed, and stirring was continued for 4 h. After the pyridine hydrochloride had been filtered and washed quickly with ether, the solvent was evaporated and the residue was heated at 60-80° C. for 30 min. Any N-sulfinylcarbamate present was then removed by evacuating the flask to a pressure of 0.5 mmHg for 10 min. (In a repetition of the experiment, the yield of methyl N-sulfinylcarbamate that could be distilled from the product was <4%.) The reaction with 14.1 g (0.20 mol) of 2-methyl-2-butane was carried out exactly as in Kresze, G., Braxmeier, H., Munsterer, H., Org. Synth., 1993, Coll. Vol. 8, 427. |
With pyridine; thionyl chloride In diethyl ether at 0℃; for 3.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In ethyl acetate at 80 - 90℃; for 0.5h; | |
70% | In ethyl acetate at 80 - 90℃; for 0.333333h; | |
67% | In benzene for 48h; Heating; |
61.1% | With trifluoroacetic acid In acetic anhydride | |
52% | With sulfuric acid In toluene at 140℃; for 1h; Inert atmosphere; Dean-Stark; | N,N'-Di(methoxycarbonyl)phenylmethanediamine Methyl carbamate (1.66 g, 22.1 mmol)was placed in a two-necked flask equipped with a Dean-Stark apparatus. Toluene(15 mL), benzaldehyde (0.73 mL, 7.17 mmol),and conc. H2SO4 (7.0 μL, 0.13 mmol)were added successively and stirred. The mixture was heated to reflux (bathtemp: 140 °C) and stirred for 1 h. The reaction mixture was cooled to rt andsubjected to suction filtration. The white precipitate obtained wassuccessively washed with water, EtOH, AcOEt, and hexane. Purification of the crude product byrecrystallization from PhMe gave the title compound 4a (890 mg, 3.73 mmol, 52%)as a white solid. Mp 180-181 °C. IR(nujol) 3304, 1711, 1548 cm-1; 1H NMR (CDCl3) d 3.71 (s, 6H), 5.74 (br. s, 2H), 6.23 (t, J = 7.6 Hz, 1H), 7.32-7.41 (m, 5H); 13CNMR (DMSO-d6) d 51.8, 61.8, 126.6, 128.0, 128.5, 140.4, 156.0;MS m/z (relative intensity) 238 (M+,1.4), 179 (M+ - CO2Me, 100). Anal. Calcd for C11H14N2O4:C, 55.46; H, 5.92; N, 11.76. Found: C, 55.42; H, 5.87; N, 11.66. |
With boron trifluoride diethyl etherate In diethyl ether at 20℃; for 18h; Inert atmosphere; | Procedure K6: Synthesis of N,N'-Di(methoxycarbonyl)phenylmethanediamine BF3•OEt2 (0.62 mL, 5.0 mmol) was added to a stirred mixture of H2NCO2Me (3.75 g, 50.0 mmol), Et2O (25mL), and benzaldehyde (5a, 2.54 mL, 25.0 mmol) at r.t. After being stirred for 18 h, the precipitate formed was taken by suction filtration and washed successively with Et2O, saturated aqueous NaHCO3,and Et2O. After being dried under reduced pressure,6a (3.37 g, 57% yield, white solid) was obtained and used without further purification. | |
With acetic anhydride; trifluoroacetic acid for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With styrene; copper(l) chloride at 114℃; for 16h; | |
76% | With copper(l) chloride In styrene at 114℃; for 16h; | To a mixture of methyl carbamate (1.0 g, 8.54 mmol) and 2-butenoyl chloride (2.4 mL, 25.0 mmol) was added styrene (30 mL), followed by CuCl (0.1 g). The reaction mixture was stirred at 114° C. for 16 h. It was then cooled to room temperature and evaporated to give a white residue, which was dissolved in DCM and washed with water, brine and dried over MgSO4. The solution was concentrated and the addition of pentane to the residue furnished the product as a white precipitate. Yield 76% (0.93 g). m.pt. 149-150° C. 1H NMR: δ 1.94 (dd, 1H, CH3CH, 2JHH=6.8 Hz, 3JHH=1.4 Hz); 3.78 (s, 3H, OCH3); 6.84 (dd, 1H, COCH, 2JHH=15.0 Hz, 3JHH=1.3 Hz); 7.10-7.20 (m, 1H, CH3CH); 7.89 (s, br, 1H, NH). 13C NMR: δ 18.4 (CH3CH), 53.0 (OCH3), 122.7 (COCH), 146.6 (CH3CH), 152.4 (CO2), 166.1 (COCH). m/z (HR-EIMS) Expected 143.0582 (M+), observed 143.0577. Anal. calcd for C9H9NO3: C, 50.35; H, 6.34; N, 9.79%. Found: C, 50.44; H, 6.59; N, 9.94%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: (E)-1-(4-iodophenyl)ethan-1-one O-methyl oxime In 1,2-dichloro-ethane at 80℃; for 1h; Stage #2: methyl carbamate With dipotassium peroxodisulfate In 1,2-dichloro-ethane at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: (E)-acetophenone O-methyloxime In 1,2-dichloro-ethane at 80℃; for 1h; Stage #2: methyl carbamate With dipotassium peroxodisulfate In 1,2-dichloro-ethane at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: (E)-benzaldehyde O-methyloxime In 1,2-dichloro-ethane at 80℃; for 1h; Stage #2: methyl carbamate With dipotassium peroxodisulfate In 1,2-dichloro-ethane at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: p-methylbenzaldoxime methyl ether In 1,2-dichloro-ethane at 80℃; for 1h; Stage #2: methyl carbamate With dipotassium peroxodisulfate In 1,2-dichloro-ethane at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: (E)-2-chlorobenzaldehyde O-methyl oxime In 1,2-dichloro-ethane at 80℃; for 1h; Stage #2: methyl carbamate With dipotassium peroxodisulfate In 1,2-dichloro-ethane at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium hexafluorophosphate; bismuth(lll) trifluoromethanesulfonate; calcium sulfate In 1,4-dioxane at 23 - 26℃; for 0.2h; | |
94% | With aluminium(III) triflate In nitromethane at 20℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With graphene oxide supported imidazolium based dicationic ionic liquid at 80℃; for 0.1h; | General procedure for the catalytic synthesis of 1-carbamatoalkyl-2-naphthols General procedure: In a typical procedure, a mixture of aromatic aldehyde (1 mmol), 2-naphthol (1 mmol), alkyl carbamate (1.1 mmol), and DIL(at)GO (0.1 g) was added to the round bottom flask and stirred at 80 °C. The progress of reaction was monitored through TLC. After the completion of reaction, crude product was washed thoroughly with water to remove unreacted starting material. After that, ethanol was added to solid product and catalyst was separated through centrifugation. After separation, catalyst was washed with ethanol and dried under vacuum for further use. Pure 1-carbamatoalkyl-2-naphthols were obtained through solvent evaporation followed by recrystallization. All synthesized compounds were characterized by physical and spectralmethods and found in agreement with reported. |
91% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.333333h; Green chemistry; | |
90% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.333333h; |
83% | With 1-n-butyl-3-methylimidazolim bromide; toluene-4-sulfonic acid at 60℃; for 0.583333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N,N,N-triethyl-N-sulfoethanammonium chloride at 110℃; for 0.166667h; | |
95% | With trityl chloride In neat (no solvent) at 70℃; for 0.133333h; | 4.2. General procedure for the synthesis of 1-amidoalkyl(carbamatoalkyl or thioamidoalkyl)-2-naphthols (Scheme 1) General procedure: To a well-ground mixture of β-naphthol (0.288 g, 2 mmol), aldehyde (2 mmol) and amide derivatives (2.4 mmol) in a 10 mL round-bottomed flask connected to a reflux condenser, was added TrCl (0.055 g, 0.2 mmol), and the resulting mixture was stirred in an oil-bath (70 °C) for the times reported in Table 2. Afterward, petroleum ether (20 mL) was added to the reaction mixture, refluxed, and stirred for 3 min, and filtered (TrCl is soluble in petroleum ether; however, the products are insoluble in this solvent). The filtrate containing the catalyst was washed two times with 20 mL of 40% (w/v) solution of NaHSO3 in H2O/EtOH (4:1) to extract the unreacted aldehyde dissolved in the petroleum ether. The organic layer was separated and dried with CaCl2; the solvent was evaporated to give pure recycled TrCl. The solid residue was recrystallized from EtOH (95%) to give the pure product (compounds 1a-m, 2a-d, and 3a-e). |
95% | With saccharin sulfonic acid In neat (no solvent) at 70℃; for 0.0833333h; Green chemistry; |
95% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.333333h; Green chemistry; | |
95% | With nano-silica-bonded 3-(n-propyl)-1-sulfoimidazolium chloride In neat (no solvent) at 70℃; for 0.183333h; | General procedure for the production of α-carbamatoalkyl-β-naphthols To a mixture of β-naphthol (0.144 g, 1 mmol), arylaldehyde (1 mmol) and alkylcarbamate (1.3 mmol) in a test tube, was added nano-SB-[PSIM]Cl (0.01 g), and the resulting mixture was stirred magnetically at 70 °C, and after solidification of the reaction mixture with a small rod at that temperature. The mixture was cooled to room temperature, then warm EtOAc (5 mL) was added and stirred for 1 min followed by centrifugation and decanting to separate nano-SB-[PSIM]Cl (the silica-bonded IL is not soluble in warm EtOAc, but the unreacted starting materials and the product are soluble in it). The separated EtOAc was evaporated, and the solid residue was recrystallized from hot EtOH (95 %) to give the pure α-carbamatoalkyl-β-naphthol. |
94% | With a magnetite (Fe3O4 )supported -SO3H functionalized benzimidazolium based ionic liquid In neat (no solvent) at 80℃; for 0.166667h; Green chemistry; | |
90% | With 4-methyl-4-sulfonic acid morpholinium chloride In neat (no solvent) at 100℃; for 0.0333333h; | General procedure for the synthesis of carbamatoalkyl naphthols 4a-o catalyzed by IL1 and IL2. General procedure: To a mixture of β-naphthol (1 mmol), an aromatic aldehyde (1 mmol) and methyl or benzyl carbamate (1.1 mmol), IL1 or IL2 (10 mol % based on aromatic aldehyde) was added. The mixture was heated on the oil bath at 100°C for 2-5 min. The reaction was monitored by TLC. Upon completion, the reaction mixture was cooled down to room temperature and warm distilled water was added. The product was filtered off, washed repeatedly with warm distilled water and recrystallized from ethanol to give carbamatoalkyl naphthols 4a-4o. The previously known products were characterized by comparison of their melting points with those of authentic samples and in some cases by IR and 1 H NMR spectra. Structure of the new product 4g was also confirmed by 13C NMR spectrum. |
77% | With 1-n-butyl-3-methylimidazolim bromide; toluene-4-sulfonic acid at 60℃; for 0.75h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tin (IV) chloride pentahydrate In neat (no solvent) at 60℃; for 0.1h; | |
89% | With ammonium cerium (IV) nitrate at 70℃; for 1h; | Typical procedure for the synthesis of carbamatoalkyl naphthols (4) General procedure: To a mixture of β-naphthol (5 mmol), an aldehyde (5 mmol), and a carbamate (5.5 mmol), CAN (0.1 mmol) was added. The reaction mixture was magnetically stirred on a preheated water bath at 70°C. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to r.t., washed with H2O/EtOH (v/v = 1/1), and the residue was recrystallized from H2O/EtOH(v/v = 2/3). The products were characterized by m.p., IR, 1H NMR, 13C NMR and elemental analysis. Spectral data for new compounds are given below. |
89% | With 4-methyl-4-sulfonic acid morpholinium chloride In neat (no solvent) at 100℃; for 0.0666667h; | General procedure for the synthesis of carbamatoalkyl naphthols 4a-o catalyzed by IL1 and IL2. General procedure: To a mixture of β-naphthol (1 mmol), an aromatic aldehyde (1 mmol) and methyl or benzyl carbamate (1.1 mmol), IL1 or IL2 (10 mol % based on aromatic aldehyde) was added. The mixture was heated on the oil bath at 100°C for 2-5 min. The reaction was monitored by TLC. Upon completion, the reaction mixture was cooled down to room temperature and warm distilled water was added. The product was filtered off, washed repeatedly with warm distilled water and recrystallized from ethanol to give carbamatoalkyl naphthols 4a-4o. The previously known products were characterized by comparison of their melting points with those of authentic samples and in some cases by IR and 1 H NMR spectra. Structure of the new product 4g was also confirmed by 13C NMR spectrum. Methyl (2-chlorophenyl)(2-hydroxynaphthalen-1- yl)methylcarbamate (4a). IR spectrum, νmax, cm-1: 3430 (NH), 3210 (OH), 1691 (C=O). 1 H NMR spectrum, δ, ppm: 3.54 s (3H, OCH3), 6.88 d (1H, J = 8.1 Hz, CH), 7.14 d (1H, J = 8.7 Hz, Harom), 7.25-7.90 m (9H, Harom, NH), 8.02 d (1H, J = 8.7 Hz, Harom), 9.94 s (1H, OH). |
88% | With Tween 20 In water at 75 - 80℃; for 0.75h; | Synthesis of 1-carbamatoalkyl-2-naphthols; general procedure General procedure: In a typical experiment (Scheme 1), β-naphthol (2 mmol), aldehyde (2 mmol) and carbamate (2 mmol) were added to a round-bottomed flask charged with a solution of 5 wt% Tween 20 aqueous micelles (4.0 mL) under stirring. The mixture was then vigorously stirred at 75-80 °C. After completion of the condensation (monitored by TLC), the precipitate was filtered off to give the corresponding products. The crude products were recrystallised from ethanol:H2O (2:1) to afford pure 1-carbamatoalkyl-2-naphthols. The products obtained were identified by 1H NMR, and physical data (m.p.) compared with those reported in the literature (Table 3). The filtrate containing the catalyst could be reused directly for the next run without any treatment. |
87% | With copper(II) choride dihydrate In neat (no solvent) at 70℃; for 0.3h; | General procedure for the synthesis of 1-carbamatoalkyl-2-naphthols, 4 General procedure: To a mixture of 2-naphthol(5 mmol), an aldehyde (5 mmol), and a carbamate(5.5 mmol), CuCl2·2H2O (0.05 mmol) was added. Thereaction mixture was stirred on a preheated water bathat 70°C. After completion of the reaction (monitoredby TLC), the reaction mixture was cooled to RT.washed with H2O/EtOH (v/v = 1/1), and recrystallizedfrom H2O/EtOH (v/v = 2/3). The products were characterized by IR, 1H NMR, 13C NMR, LC/MS andelemental analysis. |
84% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.45h; Green chemistry; | |
83% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.416667h; | |
82% | With sulfamic acid-functionalised magnetic nanoparticles at 80℃; for 0.2h; neat (no solvent); | |
78% | With 1-n-butyl-3-methylimidazolim bromide; toluene-4-sulfonic acid at 60℃; for 0.833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 4-methyl-4-sulfonic acid morpholinium chloride In neat (no solvent) at 100℃; for 0.05h; | General procedure for the synthesis of carbamatoalkyl naphthols 4a-o catalyzed by IL1 and IL2. General procedure: To a mixture of β-naphthol (1 mmol), an aromatic aldehyde (1 mmol) and methyl or benzyl carbamate (1.1 mmol), IL1 or IL2 (10 mol % based on aromatic aldehyde) was added. The mixture was heated on the oil bath at 100°C for 2-5 min. The reaction was monitored by TLC. Upon completion, the reaction mixture was cooled down to room temperature and warm distilled water was added. The product was filtered off, washed repeatedly with warm distilled water and recrystallized from ethanol to give carbamatoalkyl naphthols 4a-4o. The previously known products were characterized by comparison of their melting points with those of authentic samples and in some cases by IR and 1 H NMR spectra. Structure of the new product 4g was also confirmed by 13C NMR spectrum. |
90% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 90℃; for 2h; Neat (no solvent); | |
90% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.383333h; Green chemistry; |
75% | With 1-n-butyl-3-methylimidazolim bromide; toluene-4-sulfonic acid at 60℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
dibutyldimethoxytin; In Triethylene glycol dimethyl ether; at 111.657 - 161.101℃; for 22h;Compresed liquid(s);Conversion of starting material; | EXAMPLE 3 This Example illustrates the actual production of DMC by one step. The reboiler of the distillation still was charged with 125 g methyl carbamate, 120 g methanol, 80 g triglyme and 25 dibutyltin dimethoxide. The reboiler temperature was maintained at 349-357 F. by controlling the overhead pressure during the 12 hours uninterrupted run. The flow rate of the overhead liquid product was set at 2 cc/min. A urea solution prepared by dissolving 105.6 g urea in 2200 g methanol was pumped into the reboiler to maintain a constant liquid level in the reboiler. The reaction was terminated after 12 hours uninterrupted operation. The result of this experiment is listed in Table 2. The change of the DMC composition in the overhead products is shown in FIG. 3. The overhead pressures at the beginning and the end of 12 hours run were 66 and 134.7 psig, respectively. The column temperatures at the bottom and top section of the column were 248 F. and 233 F. at the beginning, and 286 F. and 274 F. at the end of 12 hours, respectively. While the analysis of the sample taken from the reboiler a the end of 12 hours run indicated 3.8% dimethyl carbonate, 20.9% methanol, 21.1% methyl carbamate, 1.5% N-MMC, 52.0% triglyme, 0.2% unknown, 0.2% methylamine (or water) and 0.3% ammonia, the overhead product contained 9.0% dimethyl carbonate, 88.4% methanol, 0.1% methylamine (or water) and 2.5% ammonia. The content of urea in the bottom product sample was unknown because urea could not be analyzed by gc due to urea decomposition. The unit was shut down for the next day's run. The weight of the composite overhead product was 1054 g and the weight of the urea solution pumped into the reboiler was 1252 g. The total samples taken out from the unit was 210.8 g. There was lower liquid level in the reboiler from 8 to 12 hours on stream. The composite overhead product contained 11.5% dimethyl carbonate. A vent gas was collected for 12 hours during the reaction (very little gas volume) and the analysis of this vent gas indicated 0.05 vol % CO2 and 2.1 vol O2 indicating very little decomposition of methyl carbamate or urea. Samples of the overhead product were taken hourly over the duration of the run. The DMC concentration in these samples is illustrated in FIG. 3. The result of this experiment is summarized in Table 2. The maximum concentration of DMC was -16 wt % in the 5 hr sample. The productivity observed at 5 hr was assumed to be indicative of the space yield that could be achieved with the system under steady state conditions. The value was calculated to be -3.4 lb DMC/hr-ft3 (2 g/min×0.16/350 cm2×60 min/hr×2.2E-0.3 lb/g×2.832E+04 cm3/ft3). This value was used in sizing the reaction zone of the reactive distillation column. The run was continued the next day by pumping a mixed solution prepared by mixing 1650 g methanol with 142.5 g triglyme into the reboiler. The reboiler temperature was maintained at 348-359 F. by controlling the overhead pressure. The flow rate of the overhead liquid product was set a 2 cc/min. The reaction was terminated after 10 hours uninterrupted operation. The result of this experiment is listed in Table 2. The overhead pressures at the beginning and the end of 10 hours uninterrupted run were 232.1 and 201.7 psig, respectively. The column temperatures at the bottom and top section of the column were 248 F. and 233 F. at the beginning, and 322 F. and 313 F. at the end of 10 hours run, respectively. While the analysis of the sample taken from the reboiler at the end of 10 hours (total 22 hours from the very beginning) run indicated 1.7% dimethyl carbonate, 22.2% methanol, 1.5% methyl carbamate, 1.3% N-MMC, 71.9% triglyme, 1.3% unknowns and 0.1% air, the overhead product contained 3.8% dimethyl carbonate, 94.94% methanol and 1.2% ammonia. The content of urea in the bottom product sample was unknown, because urea could not be analyzed by gc due to urea decomposition. The weight of the composite overhead product was 956 g and the weight of the mixed solution pumped into the reboiler was 1088. The total weight of the samples taken out from the unit was 197.2 g. The total weight of the inventory material collected from the column and the reboiler was 249. The vent gas was collected during the run (very small gas volume) and it contained 10.0 vol% CO2 and 0.7 vol O2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
dibutyldimethoxytin; at 160.546 - 178.323℃; for 12h;Compresed liquid(s);Conversion of starting material; | The reaction was carried out in the reboiler (350 ml) of a distillation still. The distillation column was ¼ diameter and 18 long, which was packed with ceramic saddles. The reboiler was charged with 125 g MC (methyl carbamate), 200 g methanol and 25.3 g dibutyltin dimethoxide. The reboiler temperature was maintained at 355-363 F. by controlling the overhead pressure. The flow rate of the overhead product was set at 1.5 cc/min. Methanol was continuously pumped into the reboiler to maintain a constant liquid level in the reboiler. The reaction was carried out for 6 hours each day for 2 days, for a total of 12 hours. After a 6 hour run, the unit was shut down. On the following day the unit was restarted. During the reaction the overhead liquid products were collected into a reservoir. At the end of the run all the composite overhead liquid product in the reservoir and the inventory materials in the reboiler and column were removed from the system and weighted and then analyzed. During the run the samples taken from the unit for analysis were also weighted. The result is listed in Table 1. The change in the compositions of DMC and methylamine in the overhead liquid products during the run is illustrated in FIGS. 1 and 2, respectively. The overhead pressure at 355 F. at the beginning and the end were 268.4 and 374.4 psig, respectively. The column temperatures at the bottom and top section of the column were 332 F. and 321 F. at the beginning, and 353 F. and 348 F. at the end of 12 hours run. The analysis of the bottom product sample taken from the reboiler at the end of 12 hours indicated trace ammonia, 6.9% DMC, 3.6% N-MMC, 2.1% MC, 86.6% methanol, and 0.7% others. The overhead product contained 2.1% DMC and 2.5% methylamine. The content of urea in the bottom product sample was unknown because urea could not be analyzed by gas chromatography due to urea decomposition. | |
dibutyldimethoxytin; In Triethylene glycol dimethyl ether; at 93.3233 - 142.212℃; for 12h;Compresed liquid(s);Conversion of starting material; | The reboiler of the distillation still was charged with 125 g MC, 100 g methanol, 100 g triglyme and 24.7 g dibutyltin dimethoxide. The reboiler temperature was maintained at 355-363 F. by controlling the overhead pressure. The flowrate of the overhead liquid product was set at 1.5 cc/min. To maintain a constant liquid level in the reboiler, a mixture of methanol and triglyme was prepared by mixing 1650 g methanol with 142.5 g triglyme was continuously pumped into the reboiler. The reaction was carried out for 6 hours each day for 2 days, for a total of 12 hours. The result of this experiment is listed in Table 1. The change in the compositions of DMC and methylamine in the overhead liquid products during the run are illustrated in FIGS. 1 and 2, respectively. The overhead pressures at 355 F. at the beginning and the end were 53.4 psig and 139 psig, respectively. The column temperatures at the bottom and top section of the column were 234 F. and 200 F. at the beginning, and 288 F. and 277 F. at the end of 12 hours run. The analysis of the bottom product sample taken from the reboiler at the end of 12 hours run indicated 0.1% ammonia, 4.1% DMC, 0.3%N-MMC, 2.7% MC, 32.6% methanol, and 60.2% triglyme. The overhead product contained 6.9% dimethyl carbonate. The content of urea could not be analyzed by gas chromatography due to decomposition of urea. Example 2 demonstrates the superior yield and selectivity for DMC of the present invention compared with the prior art (the Example 1). It also demonstrates that the reaction can be carried out under much lower pressure in the presence of the high boiling electron donating oxygen containing solvent, resulting in fast removal of the products DMC and ammonia from the reaction zone as soon as they are produced. Because of the fast removal of the products DMC and ammonia from the reaction zone and the novel organotin complex catalyst Bu2Sn(OCH3)2.chiL (chi=1 or 2), the superior selectivity to DMC is obtained. The DMC content in the overhead liquid product of the present invention was at least 3 times higher than the dibutyltin dimethoxide catalyst alone and in the absence of the solvent triglyme (Example 1). Consequently the separation of dimethyl carbonate from the overhead product can be achieved at much lower cost and much reduced amount of material recycle. The low reactor pressure and non-corrosive reaction system results in a great cost advantage from prior systems. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With lithium tert-butoxide In tetrahydrofuran at 20℃; for 2h; | 19 EXAMPLE 19Production of methyl (R)-{3-[4-(trifluoromethyl)phenylamino]-pentanoyl}carbamate EXAMPLE 19 Production of methyl (R)-{3-[4-(trifluoromethyl)phenylamino]-pentanoyl}carbamate 866 mg (3.57 mmol) of (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone produced in Example 6 and 402 mg (5.4 mmol) of methyl carbamate were dissolved in tetrahydrofuran (15ML) and further mixed with a lithium tert-butoxide/tetrahydrofuran solution (1 mol/L, 5.4 ML, 5.4 mmol) at room temperature.After stirring at the same temperature for 2 hours, water (5.0 ML) was further added to the reaction solution and extraction with toluene (10 ML) was repeated twice.The residue obtained by concentration of the separated organic layer after washing with water was purified on silica gel column chromatography to obtain methyl (R)-{3-[4-(trifluoromethyl)phenylamino]-pentanoyl}carbamate as a white solid (897 mg, isolated yield: 79%). 1H-NMR (CDCl3, 400 MHz/ppm): 5 0.98 (3 H, t), 1.5-1.8 (2H, m), 2.9-3.2 (2H, m), 3.77 (3H, s), 3.8-3.9 (1H, m), 4.2-4.3 (1H, br), 6.60 (2H, d), 7.37 (2H, d), 7.9-8.1 (1H, br) |
Yield | Reaction Conditions | Operation in experiment |
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dibutyldimethoxytin; In Triethylene glycol dimethyl ether; at 173.879℃; under 5311.07 Torr; for 1500h; | The purpose of this experiment is demonstrating a primary reactor system, which is composed of multiple reactors. The same experimental set-up in Example 2 was used to demonstrate the performance of the second primary reactor. The experiment was carried out in the similar manner to the Experiment 2. The present example differs from the Example 2 in that the 8 wt. % DMC solution in methanol is used herein in the place of pure methanol in the Experiment 2 and a slightly lower overhead pressure (88 psig) in the present distillation column. The reboiler of the distillation column was loaded with the following materials; 285 grams of triglyme, 40 grams of methanol and 100 grams of dibutyltin dimethoxide. A steady state operation of the distillation column reactor was obtained, while pumping in MC solution and DMC-methanol solution to the reactor. The reactor operation was continued for more than 1500 hours without interruption at 345 F. for the liquid reaction medium in the reboiler, the distillation column temperature of 278 F., and 88 psig for the overhead column pressure. The average compositions of the overhead and bottom products from the reactor during the 54 hours from 1428 hours to 1482 hours of on-stream-time are listed in Table 2. During this period, the pumping rate of a 22.5 wt. % MC solution (590 ppm H2O) was fixed at 1.97 ml/min and the pumping rate of a 8 wt. % DMC solution (80 ppm H2O) was about 3.2 ml/min at 345 F. The mole ratio of MC/CH3OH and DMC wt. % based on MC and CH3OH in the liquid medium in the reactor are 0.915 and 6.40 wt. % respectively. The result of the experiment corresponds to better than 93 mole % of MC to DMC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
dibutyldimethoxytin; In Triethylene glycol dimethyl ether; at 173.879℃; under 5455.88 Torr; for 926h; | A one liter stirred autoclave serves as the reaction zone and reboiler for the reaction/distillation column reactor, which is connected to a 1 inch diameter×3.5 feet long distillation column. The distillation column has three zone heaters, which are independently controlled. The overhead vapor stream from the distillation column is diluted with a nitrogen stream (800 cc/min) and then partially cooled to about 200 F. with hot water in a condenser. The vapor stream from the condenser cooled to ambient temperature to prevent the plugging problem of a cold spot and overhead backpressure regulator. The liquid stream from the condenser flows to a small overhead liquid reflux drum. The temperature of the liquid reflux drum is maintained at ambient temperature. The flow of the liquid product from the overhead reflux drum is monitored with a LFM (liquid flow meter). The liquid stream from the overhead reflux drum and the cooled vapor stream are combined as product stream from the reaction/distillation reactor. Samples are taken for analyses to determine the composition of the overhead vapor stream coming out of the column. Also occasionally samples are taken from the reboiler to monitor the composition of the liquid reaction medium. Whenever the samples are taken from the reboiler, the make-up solutions are pumped in to compensate for the loss of triglyme and catalyst. During the operation of the reactor, the liquid level inside the reboiler is maintained at a constant level. A vertical sight glass is attached to the reboiler for the visual observation of the liquid level inside the reboiler during the operation. Also the reboiler is equipped with a liquid level digital monitor for the automatic control of the reactor during the night and weekends for unattended operation. To carry out the operation of the primary reactor to produce DMC, a MC feed solution (methyl carbamate in methanol) and a methanol feed are pumped in and combined into a single stream. The combined feed stream is passed through a prereactor (a vertically mounted tubular reactor up-flow) at 300 F. and 230 psig to remove water in the feed streams and then introduced to the primary reactor. The temperature of the liquid reaction medium is controlled by adjusting the overhead pressure of the distillation column and the concentration of high boiling solvent in the reboiler of the distillation column. The products DMC, ammonia and other light by-products such as dimethyl ether and CO2 are boiled off from the liquid medium and carried away along with methanol vapor. The operation of the distillation column is carried out in the unconventional mode to perform partial condensation of the vapor coming out of the liquid medium in the reboiler without liquid reflux from the overhead reflux drum by controlling the vapor temperature, which is done by controlling the zone temperatures of the column with three column zone heaters, while the vapor is coming up the distillation column. It was discovered that the unconventional column operation keeps the triglyme solvent in the reactor and continuously removes the by-product N-MMC along with MC from the liquid reaction medium as a part of the overhead stream, which allows the operation of the reactor for an extended period of time. It is found that no liquid reflux from the overhead reflux drum is highly preferred in minimizing the formation of the by-product N-MMC and heterocyclic compounds. It was possible to operate the reaction/distillation column reactor more than 1000 hours without interruption until a high pressure nitrogen valve to the reboiler was accidentally opened. Operating the distillation column in the conventional way causes shutdown or removal of materials from the reboiler, because of the overflow of the reboiler due to the accumulation of the reaction by-products such as N-MMC, cyanuric acid and TTT (1,3,5-trimethyl triazine-2,4,6-trione), etc. Other critical factors to minimize the side-reactions while maintaining an acceptable DMC production rate are balancing the concentrations of solvent and catalyst, the temperature of liquid medium and the overhead column pressure. The range of optimum operation for the reboiler temperature and the overhead column pressure is from about 330 to about 355 F. for the reboiler temperature and from about 80 to about 110 psig respectively. Detailed Description of the Experiment The reboiler of the distillation column was loaded with the following materials; 285 grams of triglyme, 100 grams of methanol and 100 grams of dibutyltin dimethoxide. A steady state operation of the reaction/distillation column reactor was obtained, while pumping in the 13.3 wt. % MC solution in methanol (280 ppm H2O) at a fixed rate of 3.01 ml/min and about 1.92 ml/min of methanol (80 ppm H2O) at 345 F. for the liquid reaction medium in the reboiler, 260 F. for the vapor temperature in the top section of the distillation column, and 90.8 psig for the overhead column pressure. The flow rate... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(step [A]) A 500-milliliter three-necked flask fitted with a stirrer, a reflux condenser and a thermometer was charged with 236.3 g (2.00 mols) of methyl 2-hydroxyisobutyrate, 60.1 g (1.00 mol) of urea and 1.5 g of lead oxide, and the mixture was heat-refluxed at 140C and 700 torr while being stirred. After the reaction was conducted for 3 hours, the temperature of the reaction solution reached 170 C Thereaction solution was cooled to obtain 247.7 g of the reaction solution. The composition of the reaction solution was analyzed through liquid chromatography. Consequently, unreacted methyl 2-hydroxyisobutyrate was 104.3 g, 5,5-dimethyl-2,4-oxazolidinedione formed was 121.9 g, byproduct 2-hydroxyisobutyric acid amide was 11.8 g, and by-product methyl carbamate was 3.1 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With N-methyldidecylamine at 140℃; for 3.5h; | XIA.a A mixture containing 50 g (0.67 mole) of methyl carbamate, 272 g (3.20 moles) of pyrrolidone, 2.4 g of TK-1 tin catalyst, and 2.4 g of DAMA-10 was heated at 140[deg.] C. under 40-50 mm Hg pressure for 3.5 hours. The methanol produced by the reaction was collected in a dry ice-acetone trap during the reaction. The reaction mixture was then analyzed with GLC (internal standard method). The results indicated that the yield of pyrrolidone urea was 85% based on methyl carbamate charged, and 10% of the starting methyl carbamate still remained in the reaction mixture. The reaction mixture was then distilled under reduced pressure to remove excess pyrrolidone and the remaining methyl carbamate. The residue was stirred with 200 ml of toluene for 15 minutes and filtered. The collected solid was washed with toluene and air-dried to afford 46 g (54%) of the desired product; mp 142[deg.]-144[deg.] C. (lit. mp 142[deg.]-143[deg.] C.); IR (cm): 3360, 1710, 1660, 1590, 1370, 1250; <1>H-NMR (CDCl3): [delta]8.2 (s, 1 H), 5.9 (s, 1 H), 3.9 (t, 2 H), 2.6 (t, 2 H), 2.1 (t, 2 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With nano-silica-bonded 3-(n-propyl)-1-sulfoimidazolium chloride In neat (no solvent) at 70℃; for 0.133333h; | General procedure for the production of α-carbamatoalkyl-β-naphthols To a mixture of β-naphthol (0.144 g, 1 mmol), arylaldehyde (1 mmol) and alkylcarbamate (1.3 mmol) in a test tube, was added nano-SB-[PSIM]Cl (0.01 g), and the resulting mixture was stirred magnetically at 70 °C, and after solidification of the reaction mixture with a small rod at that temperature. The mixture was cooled to room temperature, then warm EtOAc (5 mL) was added and stirred for 1 min followed by centrifugation and decanting to separate nano-SB-[PSIM]Cl (the silica-bonded IL is not soluble in warm EtOAc, but the unreacted starting materials and the product are soluble in it). The separated EtOAc was evaporated, and the solid residue was recrystallized from hot EtOH (95 %) to give the pure α-carbamatoalkyl-β-naphthol. |
97% | With trityl chloride In neat (no solvent) at 70℃; for 0.116667h; | 4.2. General procedure for the synthesis of 1-amidoalkyl(carbamatoalkyl or thioamidoalkyl)-2-naphthols (Scheme 1) General procedure: To a well-ground mixture of β-naphthol (0.288 g, 2 mmol), aldehyde (2 mmol) and amide derivatives (2.4 mmol) in a 10 mL round-bottomed flask connected to a reflux condenser, was added TrCl (0.055 g, 0.2 mmol), and the resulting mixture was stirred in an oil-bath (70 °C) for the times reported in Table 2. Afterward, petroleum ether (20 mL) was added to the reaction mixture, refluxed, and stirred for 3 min, and filtered (TrCl is soluble in petroleum ether; however, the products are insoluble in this solvent). The filtrate containing the catalyst was washed two times with 20 mL of 40% (w/v) solution of NaHSO3 in H2O/EtOH (4:1) to extract the unreacted aldehyde dissolved in the petroleum ether. The organic layer was separated and dried with CaCl2; the solvent was evaporated to give pure recycled TrCl. The solid residue was recrystallized from EtOH (95%) to give the pure product (compounds 1a-m, 2a-d, and 3a-e). |
97% | With a magnetite (Fe3O4 )supported -SO3H functionalized benzimidazolium based ionic liquid In neat (no solvent) at 80℃; for 0.0666667h; Green chemistry; |
96% | With tin (IV) chloride pentahydrate In neat (no solvent) at 60℃; for 0.1h; | |
96% | With graphene oxide supported imidazolium based dicationic ionic liquid at 80℃; for 0.05h; | General procedure for the catalytic synthesis of 1-carbamatoalkyl-2-naphthols General procedure: In a typical procedure, a mixture of aromatic aldehyde (1 mmol), 2-naphthol (1 mmol), alkyl carbamate (1.1 mmol), and DIL(at)GO (0.1 g) was added to the round bottom flask and stirred at 80 °C. The progress of reaction was monitored through TLC. After the completion of reaction, crude product was washed thoroughly with water to remove unreacted starting material. After that, ethanol was added to solid product and catalyst was separated through centrifugation. After separation, catalyst was washed with ethanol and dried under vacuum for further use. Pure 1-carbamatoalkyl-2-naphthols were obtained through solvent evaporation followed by recrystallization. All synthesized compounds were characterized by physical and spectralmethods and found in agreement with reported. |
95% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 90℃; Neat (no solvent); | |
95% | With N,N,N-triethyl-N-sulfoethanammonium chloride at 110℃; for 0.166667h; | |
95% | With saccharin sulfonic acid In neat (no solvent) at 70℃; for 0.0833333h; Green chemistry; | |
95% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.283333h; Green chemistry; | |
95% | With copper(II) choride dihydrate In neat (no solvent) at 70℃; for 0.3h; | General procedure for the synthesis of 1-carbamatoalkyl-2-naphthols, 4 General procedure: To a mixture of 2-naphthol(5 mmol), an aldehyde (5 mmol), and a carbamate(5.5 mmol), CuCl2·2H2O (0.05 mmol) was added. Thereaction mixture was stirred on a preheated water bathat 70°C. After completion of the reaction (monitoredby TLC), the reaction mixture was cooled to RT.washed with H2O/EtOH (v/v = 1/1), and recrystallizedfrom H2O/EtOH (v/v = 2/3). The products were characterized by IR, 1H NMR, 13C NMR, LC/MS andelemental analysis. |
95% | With 4-methyl-4-sulfonic acid morpholinium chloride In neat (no solvent) at 100℃; for 0.0333333h; | General procedure for the synthesis of carbamatoalkyl naphthols 4a-o catalyzed by IL1 and IL2. General procedure: To a mixture of β-naphthol (1 mmol), an aromatic aldehyde (1 mmol) and methyl or benzyl carbamate (1.1 mmol), IL1 or IL2 (10 mol % based on aromatic aldehyde) was added. The mixture was heated on the oil bath at 100°C for 2-5 min. The reaction was monitored by TLC. Upon completion, the reaction mixture was cooled down to room temperature and warm distilled water was added. The product was filtered off, washed repeatedly with warm distilled water and recrystallized from ethanol to give carbamatoalkyl naphthols 4a-4o. The previously known products were characterized by comparison of their melting points with those of authentic samples and in some cases by IR and 1 H NMR spectra. Structure of the new product 4g was also confirmed by 13C NMR spectrum. |
92% | With silica perchloric acid at 85℃; for 2h; Neat (no solvent); | |
92% | With ammonium cerium (IV) nitrate at 70℃; for 0.6h; | Typical procedure for the synthesis of carbamatoalkyl naphthols (4) General procedure: To a mixture of β-naphthol (5 mmol), an aldehyde (5 mmol), and a carbamate (5.5 mmol), CAN (0.1 mmol) was added. The reaction mixture was magnetically stirred on a preheated water bath at 70°C. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to r.t., washed with H2O/EtOH (v/v = 1/1), and the residue was recrystallized from H2O/EtOH(v/v = 2/3). The products were characterized by m.p., IR, 1H NMR, 13C NMR and elemental analysis. Spectral data for new compounds are given below. |
91% | With Tween 20 In water at 75 - 80℃; for 0.5h; | Synthesis of 1-carbamatoalkyl-2-naphthols; general procedure General procedure: In a typical experiment (Scheme 1), β-naphthol (2 mmol), aldehyde (2 mmol) and carbamate (2 mmol) were added to a round-bottomed flask charged with a solution of 5 wt% Tween 20 aqueous micelles (4.0 mL) under stirring. The mixture was then vigorously stirred at 75-80 °C. After completion of the condensation (monitored by TLC), the precipitate was filtered off to give the corresponding products. The crude products were recrystallised from ethanol:H2O (2:1) to afford pure 1-carbamatoalkyl-2-naphthols. The products obtained were identified by 1H NMR, and physical data (m.p.) compared with those reported in the literature (Table 3). The filtrate containing the catalyst could be reused directly for the next run without any treatment. |
90% | With titania-supported perchloric acid at 90℃; for 0.0666667h; | |
89% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.25h; | |
87% | With sodium hydrogen sulfate; silica gel at 100℃; for 2h; | |
87% | With sulfamic acid-functionalised magnetic nanoparticles at 80℃; for 0.0666667h; neat (no solvent); | |
85% | With 4-imidazol-1-ylbutane-1-sulfonic acid at 80℃; for 1.5h; Neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With trityl chloride In neat (no solvent) at 70℃; for 0.133333h; | 4.2. General procedure for the synthesis of 1-amidoalkyl(carbamatoalkyl or thioamidoalkyl)-2-naphthols (Scheme 1) General procedure: To a well-ground mixture of β-naphthol (0.288 g, 2 mmol), aldehyde (2 mmol) and amide derivatives (2.4 mmol) in a 10 mL round-bottomed flask connected to a reflux condenser, was added TrCl (0.055 g, 0.2 mmol), and the resulting mixture was stirred in an oil-bath (70 °C) for the times reported in Table 2. Afterward, petroleum ether (20 mL) was added to the reaction mixture, refluxed, and stirred for 3 min, and filtered (TrCl is soluble in petroleum ether; however, the products are insoluble in this solvent). The filtrate containing the catalyst was washed two times with 20 mL of 40% (w/v) solution of NaHSO3 in H2O/EtOH (4:1) to extract the unreacted aldehyde dissolved in the petroleum ether. The organic layer was separated and dried with CaCl2; the solvent was evaporated to give pure recycled TrCl. The solid residue was recrystallized from EtOH (95%) to give the pure product (compounds 1a-m, 2a-d, and 3a-e). |
98% | With nano-silica-bonded 3-(n-propyl)-1-sulfoimidazolium chloride In neat (no solvent) at 70℃; for 0.15h; | General procedure for the production of α-carbamatoalkyl-β-naphthols To a mixture of β-naphthol (0.144 g, 1 mmol), arylaldehyde (1 mmol) and alkylcarbamate (1.3 mmol) in a test tube, was added nano-SB-[PSIM]Cl (0.01 g), and the resulting mixture was stirred magnetically at 70 °C, and after solidification of the reaction mixture with a small rod at that temperature. The mixture was cooled to room temperature, then warm EtOAc (5 mL) was added and stirred for 1 min followed by centrifugation and decanting to separate nano-SB-[PSIM]Cl (the silica-bonded IL is not soluble in warm EtOAc, but the unreacted starting materials and the product are soluble in it). The separated EtOAc was evaporated, and the solid residue was recrystallized from hot EtOH (95 %) to give the pure α-carbamatoalkyl-β-naphthol. |
97% | With saccharin sulfonic acid In neat (no solvent) at 70℃; for 0.166667h; Green chemistry; |
97% | With a magnetite (Fe3O4 )supported -SO3H functionalized benzimidazolium based ionic liquid In neat (no solvent) at 80℃; for 0.0666667h; Green chemistry; | |
96% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 90℃; Neat (no solvent); | |
96% | With N,N,N-triethyl-N-sulfoethanammonium chloride at 110℃; for 0.166667h; | |
96% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.25h; Green chemistry; | |
96% | With Nano silica phosphoric acid In neat (no solvent) at 80℃; for 0.916667h; | |
96% | With graphene oxide supported imidazolium based dicationic ionic liquid at 80℃; for 0.05h; | General procedure for the catalytic synthesis of 1-carbamatoalkyl-2-naphthols General procedure: In a typical procedure, a mixture of aromatic aldehyde (1 mmol), 2-naphthol (1 mmol), alkyl carbamate (1.1 mmol), and DIL(at)GO (0.1 g) was added to the round bottom flask and stirred at 80 °C. The progress of reaction was monitored through TLC. After the completion of reaction, crude product was washed thoroughly with water to remove unreacted starting material. After that, ethanol was added to solid product and catalyst was separated through centrifugation. After separation, catalyst was washed with ethanol and dried under vacuum for further use. Pure 1-carbamatoalkyl-2-naphthols were obtained through solvent evaporation followed by recrystallization. All synthesized compounds were characterized by physical and spectralmethods and found in agreement with reported. |
94% | With copper(II) choride dihydrate In neat (no solvent) at 70℃; for 0.4h; | General procedure for the synthesis of 1-carbamatoalkyl-2-naphthols, 4 General procedure: To a mixture of 2-naphthol(5 mmol), an aldehyde (5 mmol), and a carbamate(5.5 mmol), CuCl2·2H2O (0.05 mmol) was added. Thereaction mixture was stirred on a preheated water bathat 70°C. After completion of the reaction (monitoredby TLC), the reaction mixture was cooled to RT.washed with H2O/EtOH (v/v = 1/1), and recrystallizedfrom H2O/EtOH (v/v = 2/3). The products were characterized by IR, 1H NMR, 13C NMR, LC/MS andelemental analysis. |
93% | With silica perchloric acid at 85℃; for 2.5h; Neat (no solvent); | |
92% | With ammonium cerium (IV) nitrate at 70℃; for 0.7h; | Typical procedure for the synthesis of carbamatoalkyl naphthols (4) General procedure: To a mixture of β-naphthol (5 mmol), an aldehyde (5 mmol), and a carbamate (5.5 mmol), CAN (0.1 mmol) was added. The reaction mixture was magnetically stirred on a preheated water bath at 70°C. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to r.t., washed with H2O/EtOH (v/v = 1/1), and the residue was recrystallized from H2O/EtOH(v/v = 2/3). The products were characterized by m.p., IR, 1H NMR, 13C NMR and elemental analysis. Spectral data for new compounds are given below. |
92% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.166667h; | |
90% | With titania-supported perchloric acid at 90℃; for 0.0833333h; | |
89% | With sodium hydrogen sulfate; silica gel at 100℃; for 2.5h; | |
88% | With 4-imidazol-1-ylbutane-1-sulfonic acid at 80℃; for 1.5h; Neat (no solvent); | |
88% | With tin (IV) chloride pentahydrate In neat (no solvent) at 60℃; for 0.1h; | |
86% | With sulfamic acid-functionalised magnetic nanoparticles at 80℃; for 0.0833333h; neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.416667h; Green chemistry; | |
93% | With tin (IV) chloride pentahydrate In neat (no solvent) at 60℃; for 0.2h; | |
91% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 90℃; for 1h; Neat (no solvent); |
91% | With titania-supported perchloric acid at 90℃; for 0.05h; | |
90% | With copper(II) choride dihydrate In neat (no solvent) at 70℃; for 0.5h; | General procedure for the synthesis of 1-carbamatoalkyl-2-naphthols, 4 General procedure: To a mixture of 2-naphthol(5 mmol), an aldehyde (5 mmol), and a carbamate(5.5 mmol), CuCl2·2H2O (0.05 mmol) was added. Thereaction mixture was stirred on a preheated water bathat 70°C. After completion of the reaction (monitoredby TLC), the reaction mixture was cooled to RT.washed with H2O/EtOH (v/v = 1/1), and recrystallizedfrom H2O/EtOH (v/v = 2/3). The products were characterized by IR, 1H NMR, 13C NMR, LC/MS andelemental analysis. |
90% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.5h; | |
89% | With sulfamic acid-functionalised magnetic nanoparticles at 80℃; for 0.15h; neat (no solvent); | |
88% | With ammonium cerium (IV) nitrate at 70℃; for 1h; | Typical procedure for the synthesis of carbamatoalkyl naphthols (4) General procedure: To a mixture of β-naphthol (5 mmol), an aldehyde (5 mmol), and a carbamate (5.5 mmol), CAN (0.1 mmol) was added. The reaction mixture was magnetically stirred on a preheated water bath at 70°C. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to r.t., washed with H2O/EtOH (v/v = 1/1), and the residue was recrystallized from H2O/EtOH(v/v = 2/3). The products were characterized by m.p., IR, 1H NMR, 13C NMR and elemental analysis. Spectral data for new compounds are given below. |
86% | With Tween 20 In water at 75 - 80℃; for 1h; | Synthesis of 1-carbamatoalkyl-2-naphthols; general procedure General procedure: In a typical experiment (Scheme 1), β-naphthol (2 mmol), aldehyde (2 mmol) and carbamate (2 mmol) were added to a round-bottomed flask charged with a solution of 5 wt% Tween 20 aqueous micelles (4.0 mL) under stirring. The mixture was then vigorously stirred at 75-80 °C. After completion of the condensation (monitored by TLC), the precipitate was filtered off to give the corresponding products. The crude products were recrystallised from ethanol:H2O (2:1) to afford pure 1-carbamatoalkyl-2-naphthols. The products obtained were identified by 1H NMR, and physical data (m.p.) compared with those reported in the literature (Table 3). The filtrate containing the catalyst could be reused directly for the next run without any treatment. |
84% | With sodium hydrogen sulfate; silica gel at 100℃; for 6h; | |
78% | With silica perchloric acid at 85℃; for 8.5h; Neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With trityl chloride In neat (no solvent) at 70℃; for 0.0666667h; | 4.2. General procedure for the synthesis of 1-amidoalkyl(carbamatoalkyl or thioamidoalkyl)-2-naphthols (Scheme 1) General procedure: To a well-ground mixture of β-naphthol (0.288 g, 2 mmol), aldehyde (2 mmol) and amide derivatives (2.4 mmol) in a 10 mL round-bottomed flask connected to a reflux condenser, was added TrCl (0.055 g, 0.2 mmol), and the resulting mixture was stirred in an oil-bath (70 °C) for the times reported in Table 2. Afterward, petroleum ether (20 mL) was added to the reaction mixture, refluxed, and stirred for 3 min, and filtered (TrCl is soluble in petroleum ether; however, the products are insoluble in this solvent). The filtrate containing the catalyst was washed two times with 20 mL of 40% (w/v) solution of NaHSO3 in H2O/EtOH (4:1) to extract the unreacted aldehyde dissolved in the petroleum ether. The organic layer was separated and dried with CaCl2; the solvent was evaporated to give pure recycled TrCl. The solid residue was recrystallized from EtOH (95%) to give the pure product (compounds 1a-m, 2a-d, and 3a-e). |
97% | With nano-silica-bonded 3-(n-propyl)-1-sulfoimidazolium chloride In neat (no solvent) at 70℃; for 0.2h; | General procedure for the production of α-carbamatoalkyl-β-naphthols To a mixture of β-naphthol (0.144 g, 1 mmol), arylaldehyde (1 mmol) and alkylcarbamate (1.3 mmol) in a test tube, was added nano-SB-[PSIM]Cl (0.01 g), and the resulting mixture was stirred magnetically at 70 °C, and after solidification of the reaction mixture with a small rod at that temperature. The mixture was cooled to room temperature, then warm EtOAc (5 mL) was added and stirred for 1 min followed by centrifugation and decanting to separate nano-SB-[PSIM]Cl (the silica-bonded IL is not soluble in warm EtOAc, but the unreacted starting materials and the product are soluble in it). The separated EtOAc was evaporated, and the solid residue was recrystallized from hot EtOH (95 %) to give the pure α-carbamatoalkyl-β-naphthol. |
94% | With N,N,N-triethyl-N-sulfoethanammonium chloride at 110℃; for 0.166667h; |
92% | With saccharin sulfonic acid In neat (no solvent) at 70℃; for 0.0833333h; Green chemistry; | |
90% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 90℃; for 1h; Neat (no solvent); | |
89% | With titania-supported perchloric acid at 90℃; for 0.0666667h; | |
89% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.416667h; Green chemistry; | |
80% | With silica perchloric acid at 85℃; for 6h; Neat (no solvent); | |
79% | With sodium hydrogen sulfate; silica gel at 100℃; for 4.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Example 1.To 0.4 g (5.33 mmol) of methyl carbamate 0.39 g (5.87 mmol) of a 50 percent aqueous solution of hydroxylamine was added and the mixture was stirred until complete dissolution at the room temperature. Then, under cooling 0.3 ml (5.77 mmol) of a 50percent aqueous solution of sodium hydroxide was added dropwise in such a way to maintain the temperature of the reaction mixture in the range of 5 to 30°C. After that, the temperature was reduced to 20 to 25°C and the mixture was stirred for another 4 hours. To the syrup obtained this way 2 ml of tetrahydrofuran, 0.47 g (2.67 mmol) of 2-acetylbenzo[b]thiophene, 62 mg (1.64 mmol) of sodium tetrahydroborate and finally 0.38 ml of methanol were added under cooling at such a rate to maintain the temperature of the reaction mixture between 10 and 400C. After the addition of methanol the mixture was stirred at the temperature of 20 to 25°C for another 75 minutes. 2 ml of acetic acid and 2 ml of concentrated hydrochloric acid were added and the reaction mixture was stirred for 3 hours at the temperature of 40 to 45°C. Then, it was cooled to 20 to 250C, neutralized with 15 ml of a 10percent aqueous solution of sodium hydroxide to pH=7 and cooled to the temperature of 20 to 25 0C. The separated precipitate was stirred for another 15 minutes at the temperature of 20 to 250C, filtered off and gradually washed on the filter with 20 ml of water, 6.5 ml of toluene, again with 5 ml of water and finally with 2 ml of toluene. After drying in a hot-air drier at 80 to 850C 0.55 g of colourless crystalline powder of N-(I- benzo[b]thien-2-ylethyl)-N-hydroxyurea was isolated in the yield of 88percent with HPLC purity of 99percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With KNO3/K2O supported on activated cenosphere; at 180℃; for 8h; | Methyl carbamate (MC) 7.5 g (100 mmol), methanol 64 g (2000 mmol) and 1 g of KNO3/K2O supported on activated cenosphere. KNO3 supported on activated cenosphere (450C) followed by calcination at 500C for 2h and 600C for 6h) were charged to a 300 ml reactor. The contents were heated to 180C with slow stirring. After attaining the temperature stirring speed was increased to 1000 rpm and the time was noted as zero time. The reaction was continued for 8 hours. Ammonia formed during the reaction was removed using cooled high pressure condenser (condenser was cooled to 15C) fitted above the gas outlet valve of the reactor. Ammonia was removed at the interval of 1 hour during the course of the reaction. After 8 h reaction the reactor was cooled to 25C. Reaction mixture was analyzed by Gas Chromatography and 21.1% MC conversion, 29% selectivity to DMC, and 9.3% selectivity to MMC was observed in the reaction. | |
With Ce-Co calcined hydrotalcite (CeCoHTlc, Ce2+/Co3+ = 2); at 190℃; for 8h; | Methyl carbamate (MC) 7.5 g (100 mmol) and methanol 64 g (2000 mmol) were charged to a 300 ml reactor with lg of calcined CeCoHTlc (x=2). The contents were heated to 190C with slow stirring. After attaining the temperature stirring speed was increased to 1000 rpm and the time was noted as zero time. The reaction was continued for 8 hours. Ammonia formed during the reaction was removed using cooled high pressure condenser (condenser was cooled to 15C) fitted above the gas outlet valve of the reactor. Ammonia was removed at the interval of 1 hour during the course of the reaction. After 8 h reaction the reactor was cooled to 25C. Reaction mixture was analyzed by Gas Chromatography. 70.5% of conversion of MC was observed with 7.5% selectivity towards dimethyl carbonate (DMC) and 22.2% selectivity towards methyl N-methyl carbamate. | |
With 1-butyl-3-methylimidazolium chloride; at 190℃; for 8h; | Example 2: Synthesis of DMC in the presence of (C4MImCI): [0035] Methyl carbamate (MC) 7.5 g (100 mmol) and methanol 64 g (2000 mmol) were charged to a 300 ml reactor with l g of IL (C4MImCl). The contents were heated to 190 C with slow stirring. After attaining the temperature stirring speed was increased to 1000 rpm and the time was noted as zero time. The reaction was continued for 8 hours. Ammonia formed during the reaction was removed using cooled high pressure condenser (condenser was cooled to 15 C) fitted above the gas outlet valve of the reactor. Ammonia was removed at the interval of 1 hour during the course of the reaction. After 8 h reaction the reactor was cooled to room temperature. Reaction mixture was analyzed by Gas Chromatography. 15.1 % of conversion of MC was observed with 19.5% selectivity towards dimethyl carbonate (DMC) and 22.7% selectivity towards MMC (Table 2). |
With 1-butyl-3-methylimidazolium Tetrafluoroborate; at 190℃; for 8h; | Example 2: Synthesis of DMC in the presence of (C4MImCI): [0035] Methyl carbamate (MC) 7.5 g (100 mmol) and methanol 64 g (2000 mmol) were charged to a 300 ml reactor with l g of IL (C4MImCl). The contents were heated to 190 C with slow stirring. After attaining the temperature stirring speed was increased to 1000 rpm and the time was noted as zero time. The reaction was continued for 8 hours. Ammonia formed during the reaction was removed using cooled high pressure condenser (condenser was cooled to 15 C) fitted above the gas outlet valve of the reactor. Ammonia was removed at the interval of 1 hour during the course of the reaction. After 8 h reaction the reactor was cooled to room temperature. Reaction mixture was analyzed by Gas Chromatography. 15.1 % of conversion of MC was observed with 19.5% selectivity towards dimethyl carbonate (DMC) and 22.7% selectivity towards MMC (Table 2). | |
With samarium(III) trifluoromethanesulfonate; at 180℃; under 12411.9 - 12929 Torr; for 8h;Inert atmosphere; | Methyl carbamate (MC) 228 g (3040 mmol) and methanol 147.5 g (4609 mmol) with 3g of Sm(CF3S03)3were charged to a 2000 ml Parr reactor connected to a nitrogen reservoir from gas inlet valve. The reservoir is fitted to reactor through constant pressure regulator which is set at 250 psi. A back pressure regulator was fitted to reactor at gas outlet valve. Back pressure regulator is set at 240 psi. The pressure difference of 10 psi was maintained between constant pressure regulator and back pressure regulator to ensure positive flow of nitrogen. This will help in stripping of CH3OH along with NH3 that is formed during reaction. The reactor was then pressurized with nitrogen atmosphere at 250 psi. The inlet valve was closed at this point keeping outlet valve open. The contents were heated to 180 C under stirring condition. After attaining the temperature the inlet valve was opened and methanol feeding was started at 7 ml/min. The reaction was continued 8h. During this period methanol along with NH3 was expelled due to the set positive pressure of nitrogen. This methanol along with dissolved NH3 was collected in a trap (cooled with ice and salt mixture) connected to BPR outlet. After completion of reaction the reactor was cooled to 25C. Reaction mixture from reactor as well as from trap was analyzed by Gas Chromatography. From GC analysis 58.12% conversion of methyl carbamate and 73.67% selectivity to DMC and 7.85% selectivity to MMC was observed in the reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 5.1 wt% Ni/Fe3O4 at 190℃; for 5h; Autoclave; Inert atmosphere; | 2.3. Catalytic activity measurement All reactions were carried out in a 90 mL stainless steel autoclave with a glass tube inside and with magnetic stirring. Amines such as 1,6-hexamethylenediamine (HDA), isophorondiamine, 4,4'-methylenedicyclohexanamine, dodecylamine, allylamine, MDA, 2,4-diaminotoluene and benzylamine, and alkyl carbamates such as MC, EC, and BC were used as substrates. Typically, 10 mmol amine, 70 mmol alkyl carbamate, 170 mmol alcohol, and 100 mg catalyst were added. Under nitrogen atmosphere, the reaction proceeded at 190 °C and 1.5-2.2 MPa pressures for 5-12 h. After reaction, the autoclave was cooled down to room temperature. The catalyst was separated and recovered using an external magnetic field. Pure compounds and corresponding isolated yields were obtained with different procedures. (I) diamines as substrates: 25 mL alcohol (methanol, ethanol, or butanol was used for reactions using MC, EC, or BC as carbonyl source, respectively) was added into the reacted mixture to dissolve the product and unreacted alkyl carbamate, and the unsolvable by-products were removed by filtration. Then, the alcohol and alkyl carbamate were removed with a rotary evaporator under vacuum and raw solid product was obtained. It was further washed with diethyl ether/hexane to remove alcohol residue and soluble impurities, and desired pure product was obtained and weighted; (II) monoamines as substrates: 25 mL ethanol was added into the reacted mixture to dissolve the products and unreacted EC, and the unsolvable byproduct was removed by filtration. Then, ethanol was removed under vacuum and _100 mL of distilled water was added into the mixture of EC and product to dissolve the unreacted EC. After filtration, the raw solid product was further washed with diethyl ether/hexane to remove ethanol residue and soluble impurities and desired product was obtained and weighted. |
96.9% | With cerium(IV) oxide at 150 - 210℃; for 6h; Inert atmosphere; | 1 Take appropriate amount of cerium nitrate in the crucible, dried in 110 ° C oven 4h, And then calcined at 600 ° C for 4 h in a muffle furnace.The calcined material is finely ground to obtain a solid Ce02 catalyst. An appropriate amount of hexamethylene diamine, methyl carbamate,Methanol (molar ratio of 1: 2: 5) were charged into a high-pressure reaction kettle with a condenser tube, At the same time, 0.5% CeO2,Heating to 150 ° C reaction 2h,And then heated to 210 ° C reaction 4h.The process of continuous access to nitrogen,The by-product ammonia gas is continuously discharged. After completion of the reaction, the catalyst was removed by hot filtration, and the resulting liquid was distilled under reduced pressure at 60 ° C and 1 KPa to obtain methyl hexamethylene diaminocarbonate as a white solid.The catalyst obtained by filtration can be repeatedly used after being washed. The results showed that the conversion of hexamethylene diamine was 100% , The yield of methyl dicarbamate was 96.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 5.1 wt% Ni/Fe3O4 at 190℃; for 5h; Autoclave; Inert atmosphere; | 2.3. Catalytic activity measurement All reactions were carried out in a 90 mL stainless steel autoclave with a glass tube inside and with magnetic stirring. Amines such as 1,6-hexamethylenediamine (HDA), isophorondiamine, 4,4'-methylenedicyclohexanamine, dodecylamine, allylamine, MDA, 2,4-diaminotoluene and benzylamine, and alkyl carbamates such as MC, EC, and BC were used as substrates. Typically, 10 mmol amine, 70 mmol alkyl carbamate, 170 mmol alcohol, and 100 mg catalyst were added. Under nitrogen atmosphere, the reaction proceeded at 190 °C and 1.5-2.2 MPa pressures for 5-12 h. After reaction, the autoclave was cooled down to room temperature. The catalyst was separated and recovered using an external magnetic field. Pure compounds and corresponding isolated yields were obtained with different procedures. (I) diamines as substrates: 25 mL alcohol (methanol, ethanol, or butanol was used for reactions using MC, EC, or BC as carbonyl source, respectively) was added into the reacted mixture to dissolve the product and unreacted alkyl carbamate, and the unsolvable by-products were removed by filtration. Then, the alcohol and alkyl carbamate were removed with a rotary evaporator under vacuum and raw solid product was obtained. It was further washed with diethyl ether/hexane to remove alcohol residue and soluble impurities, and desired pure product was obtained and weighted; (II) monoamines as substrates: 25 mL ethanol was added into the reacted mixture to dissolve the products and unreacted EC, and the unsolvable byproduct was removed by filtration. Then, ethanol was removed under vacuum and _100 mL of distilled water was added into the mixture of EC and product to dissolve the unreacted EC. After filtration, the raw solid product was further washed with diethyl ether/hexane to remove ethanol residue and soluble impurities and desired product was obtained and weighted. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 90℃; for 3h; Neat (no solvent); | |
83% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.666667h; | |
78% | With Tween 20 In water at 75 - 80℃; for 1h; | Synthesis of 1-carbamatoalkyl-2-naphthols; general procedure General procedure: In a typical experiment (Scheme 1), β-naphthol (2 mmol), aldehyde (2 mmol) and carbamate (2 mmol) were added to a round-bottomed flask charged with a solution of 5 wt% Tween 20 aqueous micelles (4.0 mL) under stirring. The mixture was then vigorously stirred at 75-80 °C. After completion of the condensation (monitored by TLC), the precipitate was filtered off to give the corresponding products. The crude products were recrystallised from ethanol:H2O (2:1) to afford pure 1-carbamatoalkyl-2-naphthols. The products obtained were identified by 1H NMR, and physical data (m.p.) compared with those reported in the literature (Table 3). The filtrate containing the catalyst could be reused directly for the next run without any treatment. |
70% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 1h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tin (IV) chloride pentahydrate In neat (no solvent) at 60℃; for 0.2h; | |
92% | With copper(II) choride dihydrate In neat (no solvent) at 70℃; for 0.3h; | General procedure for the synthesis of 1-carbamatoalkyl-2-naphthols, 4 General procedure: To a mixture of 2-naphthol(5 mmol), an aldehyde (5 mmol), and a carbamate(5.5 mmol), CuCl2·2H2O (0.05 mmol) was added. Thereaction mixture was stirred on a preheated water bathat 70°C. After completion of the reaction (monitoredby TLC), the reaction mixture was cooled to RT.washed with H2O/EtOH (v/v = 1/1), and recrystallizedfrom H2O/EtOH (v/v = 2/3). The products were characterized by IR, 1H NMR, 13C NMR, LC/MS andelemental analysis. |
92% | With Tween 20 In water at 75 - 80℃; for 0.5h; | Synthesis of 1-carbamatoalkyl-2-naphthols; general procedure General procedure: In a typical experiment (Scheme 1), β-naphthol (2 mmol), aldehyde (2 mmol) and carbamate (2 mmol) were added to a round-bottomed flask charged with a solution of 5 wt% Tween 20 aqueous micelles (4.0 mL) under stirring. The mixture was then vigorously stirred at 75-80 °C. After completion of the condensation (monitored by TLC), the precipitate was filtered off to give the corresponding products. The crude products were recrystallised from ethanol:H2O (2:1) to afford pure 1-carbamatoalkyl-2-naphthols. The products obtained were identified by 1H NMR, and physical data (m.p.) compared with those reported in the literature (Table 3). The filtrate containing the catalyst could be reused directly for the next run without any treatment. |
91% | With ammonium cerium (IV) nitrate at 70℃; for 1h; | Typical procedure for the synthesis of carbamatoalkyl naphthols (4) General procedure: To a mixture of β-naphthol (5 mmol), an aldehyde (5 mmol), and a carbamate (5.5 mmol), CAN (0.1 mmol) was added. The reaction mixture was magnetically stirred on a preheated water bath at 70°C. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to r.t., washed with H2O/EtOH (v/v = 1/1), and the residue was recrystallized from H2O/EtOH(v/v = 2/3). The products were characterized by m.p., IR, 1H NMR, 13C NMR and elemental analysis. Spectral data for new compounds are given below. |
90% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 90℃; for 1h; Neat (no solvent); | |
90% | With nano-silica-bonded 3-(n-propyl)-1-sulfoimidazolium chloride In neat (no solvent) at 70℃; for 0.233333h; | General procedure for the production of α-carbamatoalkyl-β-naphthols To a mixture of β-naphthol (0.144 g, 1 mmol), arylaldehyde (1 mmol) and alkylcarbamate (1.3 mmol) in a test tube, was added nano-SB-[PSIM]Cl (0.01 g), and the resulting mixture was stirred magnetically at 70 °C, and after solidification of the reaction mixture with a small rod at that temperature. The mixture was cooled to room temperature, then warm EtOAc (5 mL) was added and stirred for 1 min followed by centrifugation and decanting to separate nano-SB-[PSIM]Cl (the silica-bonded IL is not soluble in warm EtOAc, but the unreacted starting materials and the product are soluble in it). The separated EtOAc was evaporated, and the solid residue was recrystallized from hot EtOH (95 %) to give the pure α-carbamatoalkyl-β-naphthol. |
83% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.383333h; Green chemistry; | |
82% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triethylsilane; trifluoroacetic acid In acetonitrile at 130℃; for 1.5h; Microwave irradiation; | |
71% | With triethylsilane; trifluoroacetic acid In acetonitrile at 130℃; for 1.5h; Microwave irradiation; | 102b A 25 -mL microwave vial equipped with a magnetic stirrer was charged with 102a(1.00 g, 3.83 mmol), methyl carbamate (575 mg, 7.66 mmol), trifluoroacetic acid (871 mg, 7.66 mmol), triethylsilane (888 mg, 7.66 mmol) and acetonitrile (10 mL). The vial was loaded in a Biotage microwave and heated at 130 °C for 1.5 h. After this time, the solution was concentrated in vacuo. The resulting residue was partitioned between methylene chloride (100 mL) and a saturated aqueous sodium bicarbonate (30 mL). The aqueous layer was extracted with methylene chloride (3 x 20 mL). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 60% ethyl acetate/hexanes) to afford a 71% yield (858 mg) of 102b as a colorless oil; ]H NMR (300 MHz, CDC13) δ 7.42 (s, 1H), 7.29 (m, 1H), 7.12 (d, 1H, / = 7.7 Hz), 5.60 (br s, 1H), 4.27 (br s, 2H), 3.65 (s, 3H), 3.57 (q, 2H, / = 6.8 Hz), 3.20 (q, 2H, / = 6.7 Hz), 1.31 (s, 9H), 1.26 (t, 3H, / = 6.7 Hz), 1.09 (t, 3H, / = 6.8 Hz); MS (ESI+) m/z 321.2 (M+H) |
71% | With triethylsilane; trifluoroacetic acid In acetonitrile at 130℃; for 1.5h; Microwave irraradiation; | 103b Example 103b Methyl 5-ieri-Butyl-2-(diethylcarbamoyl)benzylcarbamate 103bA 25 -mL microwave vial equipped with a magnetic stirrer was charged with 103a (1.00 g, 3.83 mmol), methyl carbamate (575 mg, 7.66 mmol), trifluoroacetic acid (871 mg, 7.66 mmol), triethylsilane (888 mg, 7.66 mmol) and acetonitrile (10 mL). The vial was loaded in a Biotage microwave and heated at 130 °C for 1.5 h. After this time, the solution was concentrated in vacuo. The resulting residue was partitioned between methylene chloride (100 mL) and a saturated aqueous sodium bicarbonate (30 mL). The aqueous layer was extracted with methylene chloride (3 x 20 mL). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 60% ethyl acetate/hexanes) to afford a 71 % yield (858 mg) of 103b as a colorless oil; ]H NMR (300 MHz, CDC13) δ 7.42 (s, 1H), 7.29 (m, 1H), 7.12 (d, 1H, 7 = 7.7 Hz), 5.60 (br s, 1H), 4.27 (br s, 2H), 3.65 (s, 3H), 3.57 (q, 2H, / = 6.8 Hz), 3.20 (q, 2H, / = 6.7 Hz), 1.31 (s, 9H), 1.26 (t, 3H, / = 6.7 Hz), 1.09 (t, 3H, / = 6.8 Hz); MS (ESI+) m/z 321.2 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With nano-silica-bonded 3-(n-propyl)-1-sulfoimidazolium chloride In neat (no solvent) at 70℃; for 0.383333h; | General procedure for the production of α-carbamatoalkyl-β-naphthols To a mixture of β-naphthol (0.144 g, 1 mmol), arylaldehyde (1 mmol) and alkylcarbamate (1.3 mmol) in a test tube, was added nano-SB-[PSIM]Cl (0.01 g), and the resulting mixture was stirred magnetically at 70 °C, and after solidification of the reaction mixture with a small rod at that temperature. The mixture was cooled to room temperature, then warm EtOAc (5 mL) was added and stirred for 1 min followed by centrifugation and decanting to separate nano-SB-[PSIM]Cl (the silica-bonded IL is not soluble in warm EtOAc, but the unreacted starting materials and the product are soluble in it). The separated EtOAc was evaporated, and the solid residue was recrystallized from hot EtOH (95 %) to give the pure α-carbamatoalkyl-β-naphthol. |
88% | With magnesium(II) 2,2,2-trifluoroacetate at 100℃; for 0.583333h; | |
87% | With 4-methyl-4-sulfonic acid morpholinium chloride In neat (no solvent) at 100℃; for 0.0666667h; | General procedure for the synthesis of carbamatoalkyl naphthols 4a-o catalyzed by IL1 and IL2. General procedure: To a mixture of β-naphthol (1 mmol), an aromatic aldehyde (1 mmol) and methyl or benzyl carbamate (1.1 mmol), IL1 or IL2 (10 mol % based on aromatic aldehyde) was added. The mixture was heated on the oil bath at 100°C for 2-5 min. The reaction was monitored by TLC. Upon completion, the reaction mixture was cooled down to room temperature and warm distilled water was added. The product was filtered off, washed repeatedly with warm distilled water and recrystallized from ethanol to give carbamatoalkyl naphthols 4a-4o. The previously known products were characterized by comparison of their melting points with those of authentic samples and in some cases by IR and 1 H NMR spectra. Structure of the new product 4g was also confirmed by 13C NMR spectrum. |
79% | With Tween 20 In water at 75 - 80℃; for 0.833333h; | Synthesis of 1-carbamatoalkyl-2-naphthols; general procedure General procedure: In a typical experiment (Scheme 1), β-naphthol (2 mmol), aldehyde (2 mmol) and carbamate (2 mmol) were added to a round-bottomed flask charged with a solution of 5 wt% Tween 20 aqueous micelles (4.0 mL) under stirring. The mixture was then vigorously stirred at 75-80 °C. After completion of the condensation (monitored by TLC), the precipitate was filtered off to give the corresponding products. The crude products were recrystallised from ethanol:H2O (2:1) to afford pure 1-carbamatoalkyl-2-naphthols. The products obtained were identified by 1H NMR, and physical data (m.p.) compared with those reported in the literature (Table 3). The filtrate containing the catalyst could be reused directly for the next run without any treatment. |
75% | With magnesium hydrogen sulfate In neat (no solvent) at 100℃; for 0.75h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With saccharin sulfonic acid In neat (no solvent) at 70℃; for 0.583333h; Green chemistry; | |
87% | With trityl chloride In neat (no solvent) at 70℃; for 0.25h; | 4.3. General procedure for the condensation between 2- naphthol, terephthaldehyde, and amides (or alkyl carbamates) (Scheme 2) General procedure: To a well-ground mixture of β-naphthol (0.576 g, 4 mmol), terephthaldehyde (0.268 g, 2 mmol) and amide (or alkyl carbamate) (0.283 g, 4.8 mmol) in a 10 mL round-bottomed flask connected to a reflux condenser, was added TrCl (0.083 g, 0.3 mmol, 15 mol %), and the resulting mixture was stirred in an oil-bath (70 °C) for the appropriate time. After completion of the reaction, as monitored by TLC, the reaction mixture was cooled to room temperature and triturated with hot EtOH (95%) (the impurities are soluble in hot EtOH; however, the product isn't soluble in this solvent) to give pure bis[1-amidoalkyl (or carbamatoalkyl)-2-naphthol] (compounds 4a-c). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In hexane for 0.9h; Reflux; Green chemistry; | General experimental procedure for the synthesis of N,N′-alkylidenebisamide General procedure: A mixture of aldehyde (1 mmol), amide (2 mmol), n-hexane (5 ml) andnano-TiCl .SiO (0.04 g) was refluxed for appropriate time. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature and filtered. The catalyst was separated from the reaction mixture by boiling ethanol. The crude solid product was purifiedby recrystallization procedure in ethanol:water, 80:20. |
85% | With nano-SnCl4*SiO2 In hexane for 0.81h; Reflux; | |
75% | In ethyl acetate at 80 - 90℃; for 0.25h; |
49% | With sulfuric acid In toluene at 140℃; for 0.75h; Inert atmosphere; Dean-Stark; | General procedure: Methyl carbamate (1.66 g, 22.1 mmol)was placed in a two-necked flask equipped with a Dean-Stark apparatus. Toluene(15 mL), benzaldehyde (0.73 mL, 7.17 mmol),and conc. H2SO4 (7.0 μL, 0.13 mmol)were added successively and stirred. The mixture was heated to reflux (bathtemp: 140 °C) and stirred for 1 h. The reaction mixture was cooled to rt andsubjected to suction filtration. The white precipitate obtained wassuccessively washed with water, EtOH, AcOEt, and hexane. Purification of the crude product byrecrystallization from PhMe gave the title compound 4a (890 mg, 3.73 mmol, 52%)as a white solid. Mp 180-181 °C. IR(nujol) 3304, 1711, 1548 cm-1; 1H NMR (CDCl3) d 3.71 (s, 6H), 5.74 (br. s, 2H), 6.23 (t, J = 7.6 Hz, 1H), 7.32-7.41 (m, 5H); 13CNMR (DMSO-d6) d 51.8, 61.8, 126.6, 128.0, 128.5, 140.4, 156.0;MS m/z (relative intensity) 238 (M+,1.4), 179 (M+ - CO2Me, 100). Anal. Calcd for C11H14N2O4:C, 55.46; H, 5.92; N, 11.76. Found: C, 55.42; H, 5.87; N, 11.66. |
With boron trifluoride diethyl etherate In diethyl ether at 20℃; for 18h; Inert atmosphere; | Procedure K6: Synthesis of N,N'-Di(methoxycarbonyl)phenylmethanediamine General procedure: BF3•OEt2 (0.62 mL, 5.0 mmol) was added to a stirred mixture of H2NCO2Me (3.75 g, 50.0 mmol), Et2O (25mL), and benzaldehyde (5a, 2.54 mL, 25.0 mmol) at r.t. After being stirred for 18 h, the precipitate formed was taken by suction filtration and washed successively with Et2O, saturated aqueous NaHCO3,and Et2O. After being dried under reduced pressure,6a (3.37 g, 57% yield, white solid) was obtained and used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 55% 2: 5.5% | With manganese(IV) oxide In methanol at 189.84℃; for 6h; Autoclave; | 2. Experimental General procedure: All compounds were of analytical grade and used without any further purification. Metal oxides were dried at 353 K for 1 h in order to remove absorbed water.(0007)The reaction of HDA and MC was carried out in a 100 ml autoclave with a magnetic stirring. HDA (2.5 mmol), MC (5-25 mmol), corresponding alcohol and catalyst (12-35 mg) were successively charged into the reactor and reacted at 443-483 K for 2-10 h. After the reaction, the autoclave was cooled to room temperature. Catalyst and insoluble compounds were separated from reaction products by centrifugation or filtration. |
Yield | Reaction Conditions | Operation in experiment |
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With Ca-Al calcined hydrotalcite(CaAlHTlc, Ca2+/Al3+ = 3); at 180℃; for 8h; | Urea 7.5 g (125 mmol) and methanol 65 g (2030 mmol) were charged to a 300 ml reactor with lg of calcined CaAlHTlc (x=3). The contents were heated to 180C with slow stirring. After attaining the temperature stirring speed was increased to 1000 rpm and the time was noted as zero time. The reaction was continued for 8 hours. Ammonia formed during the reaction was removed using cooled high pressure condenser (condenser was cooled to 15C) fitted above the gas outlet valve of the reactor. Ammonia was removed at the interval of 1 hour during the course of the reaction. After 8 h reaction the reactor was cooled to 25C. Reaction mixture was analyzed by Gas Chromatography. 88% of conversion of urea was observed with 78 % selectivity towards MC and 1.7% selectivity towards dimethyl carbonate (DMC) and 6.3% selectivity for methyl N-methyl carbamate (MMC). |
Yield | Reaction Conditions | Operation in experiment |
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With cerium(IV) oxide; carbon dioxide at 119.84℃; for 24h; Autoclave; | Activity tests General procedure: All the reactions were carried out in an autoclave reactor withan inner volume of 190 ml. A typical procedure of the reaction of CO2 + methanol with 2-cyanopyridine was as follows: 0.34 g of CeO2 catalyst, 0.64 g of methanol (20 mmol, Wako Pure Chemical Industries, 99.8% min.), and 10.4 g of 2-cyanopyridine (100 mmol,Tokyo Chemical Industry Co., Ltd., 99.0% min.) were put into the autoclave together with a spinner, and then, the reactor was purged and pressurized with CO2 (Shimakyu Co. Ltd., >99.5%). Gas line was closed, and then, the reactor was heated to the reaction temperature. The time when the temperature reached the desired reaction temperature is defined as zero reaction time. The mixture was constantly stirred during the reaction. After the specific reaction time, the reactor was cooled to room temperature and the gas was collected. Ethanol (30 ml, Wako Pure Chemical Industries, 99.5% min.) and 1-hexanol (0.2 ml, Tokyo ChemicalIndustry Co., Ltd., 98.0% min.) were added to the liquid phase asa solvent and an internal standard substance for a quantitativeanalysis, respectively. Products in the liquid and gas phases were analyzed by using a gas chromatograph equipped with FID(Shimadzu GC-2014) and GC-MS (Shimadzu QP-2020) with a CP-Sil5 capillary column (length 50 m, i.d. 0.25 mm, film thickness0.25 μm. For the synthesis of various carbonates from CO2 and the corresponding alcohols, the procedures are the same as the case of the reaction of CO2 + methanol with 2-cyanopyridine. After the reaction time, 30 ml of ethanol or acetone (Wako Pure Chemical Industries,99.5% min.) was added to the liquid phase as a solvent, and 0.2 ml of 1-hexanol or 1-propanol (Wako Pure Chemical Industries,99.5% min.) was added to the liquid phase as an internal standard substance for a quantitative analysis. The products in the liquid and gas phases were analyzed by gas chromatography equippedwith an FID or quadrupole mass spectrometer (GC-MS) using a CP-Sil5 capillary column (length 50 m, i.d. 0.25 mm, film thickness 0.25 μm) or TC-WAX capillary column (length 30 m, i.d. 0.25 mm, film thickness 0.25 μm). |
Yield | Reaction Conditions | Operation in experiment |
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84% | With boron trifluoride diethyl etherate In diethyl ether at 20℃; for 2h; Inert atmosphere; | General procedure: An alternative method for the synthesis of 2a is as follows. Under argonatmosphere, BF3•OEt2 (0.38 mL, 3.0 mmol)was added to a mixture of methyl carbamate (5.58 g, 74.3 mmol),Et2O (38.0 mL), and benzaldehyde (3.91g, 36.9 mmol) at rt. After being stirred for 2 h, the resultantmixture was subjected to suction filtration. The white precipitate obtained wassuccessively washed with Et2O, saturated aqueous NaHCO3,and Et2O, and dried in vacuo. The white solid (4.33g, 18.2 mmol, 49%) was used without further purification |
With boron trifluoride diethyl etherate In diethyl ether at 20℃; for 18h; Inert atmosphere; | Procedure K6: Synthesis of N,N'-Di(methoxycarbonyl)phenylmethanediamine General procedure: BF3•OEt2 (0.62 mL, 5.0 mmol) was added to a stirred mixture of H2NCO2Me (3.75 g, 50.0 mmol), Et2O (25mL), and benzaldehyde (5a, 2.54 mL, 25.0 mmol) at r.t. After being stirred for 18 h, the precipitate formed was taken by suction filtration and washed successively with Et2O, saturated aqueous NaHCO3,and Et2O. After being dried under reduced pressure,6a (3.37 g, 57% yield, white solid) was obtained and used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
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5 g; 8.5 g | With methanol; at 150℃; under 3750.38 Torr; for 12h;Inert atmosphere; Autoclave; | 10g of dimethyl oxalate, 10g of urea, and 10g methanol were weighed and loaded into a 100mL reaction vessel under closed pressure with heating and stirring. It was then fed into the reactor and N2 was used to displace air in the autoclave. It was displaced 3 times. After passing N2 it was pressurized to 0.5MPa, temperature was set to 70C, and stirring was done to dissolve the staring material under heat. Setting the reaction temperature at 150C, stirring speed set to 100rpm, the reaction continued for 12h then waited until the reactor internal temperature was lowered to room temperature. The exhaust vent needle was opened then waited until pressure was reduced to 0.1MPa. The reactor was opened and the reaction mixture was taken out then placed in a rotary evaporator flask. Degree of vacuum was set to 3mmHg, temperature to 80C, and rotational speed to 100rpm. Vacuum distillation was done for 5h then collected methyl carbamate 8.5g. From urea was calculated methyl carbamate 68% yield per pass. Remaining in the flask was collected a white powder. It was washed with hot methanol solution and dried to give pure oxamide 5g. From dimethyl oxalate was calculated oxamide 67.1% yield per pass. |
Yield | Reaction Conditions | Operation in experiment |
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77% | With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 80℃; for 19h; Inert atmosphere; | methyl (7-methyl-8-nitroquinolin-2-yl)carbamate (5) Amixture of 4 (3.5 g, 16 mmol),methylcarbamate (3.0 g, 39 mmol), Cs2CO3 (12.8 g, 39mmol), Pd(OAc)2 (358 mg, 1.6 mmol), and BINAP (980 mg, 1.6 mmol) inanhydrous 1,4-dioxane (120 mL) under an atmosphere of Ar was stirred at 80°Cfor 19 h. The reaction mixture was cooled to room temperature, diluted withAcOEt filtered through a short plug of silica and concentrated. The residue waspurified by column chromatography on silica gel eluted with CHCl3 togive 5 (3.2 g, 77%) as pale greensolid. 1H NMR (CDCl3, 600 MHz): δ = 8.30 (d,H, J = 7.8 Hz), 8.12 (d, 1H, J = 7.8 Hz), 7.77 (d, 1H, J = 7.2 Hz), 7.69 (s, 1H), 7.30 (d, 1H, J = 7.2 Hz), 3.84 (s, 3H), 2.50 (s, 3H).13C NMR (CDCl3, 150 MHz): δ = 153.6, 152.2, 147.0, 138.2, 138.2, 130.7,128.8, 126.7, 124.5, 113.5, 52.9, 17.4. HRMS (ESI) m/z: calcd. for [C12H11N3O4+Na]+,262.0822; found, 284.0633. |
Yield | Reaction Conditions | Operation in experiment |
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86% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 7-methyl-3,4-dihydropyrano[3,4-e][1,3]oxazine-2,5-dione; general procedure General procedure: A mixture of 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol), and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give the pure product. 7-Methyl-4-phenyl-3,4-dihydropyrano[3,4-e][1,3]oxazine-2,5-dione (4a): Yellow powder; m.p. 143-145 °C; IR (νmax, cm-1) KBr: 3126(NH), 1680 (C=O); 1H NMR (250 MHz, CDCl3) δ 2.13 (3H, s, CH3),5.80 (1H, s, CH), 6.18 (1H, s, =CH), 7.45-7.80 (5H, m, C6H5), 10.80(1H, br. s, NH); 13C NMR (62.9 MHz, CDCl3) δ 19.9 (CH3), 34.4 (CH),103.1, 103.7, 113.6, 127.2, 127.6, 128.6, 129.2, 132.2, 161.3, 168.9; MSm/z (%): 257 (12); Anal. calcd for C14H11NO4: C, 65.37; H, 4.31; N,5.44; found: C, 65.50; H, 4.21; N, 5.57%. |
Yield | Reaction Conditions | Operation in experiment |
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93% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 7-methyl-3,4-dihydropyrano[3,4-e][1,3]oxazine-2,5-dione; general procedure General procedure: A mixture of 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol), and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 7-methyl-3,4-dihydropyrano[3,4-e][1,3]oxazine-2,5-dione; general procedure General procedure: A mixture of 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol), and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
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94% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 7-methyl-3,4-dihydropyrano[3,4-e][1,3]oxazine-2,5-dione; general procedure General procedure: A mixture of 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol), and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.3% | With hydroxylamine; sodium hydroxide; In water; at 20℃; for 3.7h; | 42 g of sodium hydroxide solid was put into 260 ml of purified water, the temperature was controlled at 20 C with ice brine, 84.7 g of methyl carbamate was added, and 66 ml of 50% (w / v) Aqueous solution, 40min drop is completed. After the dropwise addition, the reaction was incubated for 3 h.(2) The solution was adjusted to pH 7.5 with 82 ml of concentrated hydrochloric acid (37% concentration), then distilled under reduced pressure at 60 C, and about 280 ml of water was distilled off, and the precipitated sodium chloride was removed by hot filtration. The filtrate was transferred to a 3-necked flask and the temperature was raised to 60 C. 10 g of 732 cationic resin (fried dry weight) was added for decoloration for 10 minutes.(3) After the decolorization, filtration (filter out 732 cationic resin), the filtrate into the three bottles after stirring cooling, cooling to 2 C, the insulation for 50 minutes, the filter, the first filter cake Times with 28ml water washing, the second with 22ml water washing, when no liquid drops, the filter is completed, the material. Drying at 55 C for 4 hours gave 47. 34 g of hydroxyurea with a total yield of 62.3% |
Yield | Reaction Conditions | Operation in experiment |
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94.2% | With 2-(2',4’,6’-trimethylbenzyl)benzotriazolium bromide In 1,2-dichloro-benzene at 180℃; for 5h; Inert atmosphere; | 3 into a 1 L of high-pressure reaction vessel, 9.8 g of 2,4-toluenediamine, 2.4 g of 2,6-toluenediamine, 20.2 g of methyl carbamate and 166 mg of 2- (2',4’,6’-trimethylbenzyl) benzotriazole bromide salt and O-dichlorobenzene 565 mL were successively added under nitrogen atmosphere, heating to 180 ° C and keep the reactor pressure to 1.5 MPa and while stirring carried out the reaction. The progress of the reaction was monitored by liquid chromatography. After 5 hours toluenediamine was completely reacted, and the reaction was stopped. The reaction solution was cooled to room temperature and the residual ammonia was removed from the reaction vessel. Analysis by liquid chromatography, the yield of methyl toluene dicarbamate in the reaction liquid was 99.0%,; The above reaction solution was distilled under reduced pressure to remove O-dichlorobenzene and the residue was subjected to column chromatography separation using to a mixed solvent of petroleum ether and ethyl acetate as an eluent with a volume ratio of 100: 1 .to obtain toluene methyl dicarbamate, yield 94.2%. |
Yield | Reaction Conditions | Operation in experiment |
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85% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | General procedure General procedure: A mixture of 4-hydroxycoumarin (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give a pure product. |
Yield | Reaction Conditions | Operation in experiment |
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92% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | General procedure General procedure: A mixture of 4-hydroxycoumarin (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give a pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | General procedure General procedure: A mixture of 4-hydroxycoumarin (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give a pure product. |
Yield | Reaction Conditions | Operation in experiment |
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91% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | General procedure General procedure: A mixture of 4-hydroxycoumarin (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with water (15 mL) to give a pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With 4-methyl-4-sulfonic acid morpholinium chloride In neat (no solvent) at 100℃; for 0.0666667h; | General procedure for the synthesis of carbamatoalkyl naphthols 4a-o catalyzed by IL1 and IL2. General procedure: To a mixture of β-naphthol (1 mmol), an aromatic aldehyde (1 mmol) and methyl or benzyl carbamate (1.1 mmol), IL1 or IL2 (10 mol % based on aromatic aldehyde) was added. The mixture was heated on the oil bath at 100°C for 2-5 min. The reaction was monitored by TLC. Upon completion, the reaction mixture was cooled down to room temperature and warm distilled water was added. The product was filtered off, washed repeatedly with warm distilled water and recrystallized from ethanol to give carbamatoalkyl naphthols 4a-4o. The previously known products were characterized by comparison of their melting points with those of authentic samples and in some cases by IR and 1 H NMR spectra. Structure of the new product 4g was also confirmed by 13C NMR spectrum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.1% | With pyridine; tetrachloromethane; titanium(IV) oxide; vanadia; tungsten(VI) oxide; tin(IV) oxide In N,N-dimethyl-formamide at 120 - 230℃; for 32h; | 2 Example 2 A process for the synthesis of 2,4-dichloroquinazoline comprises the steps of: 1) o-aminobenzoyl chloride, carbon tetrachloride, pyridine, catalyst, mixing with the methyl carbamate of DMF,The molar ratio of o-aminobenzoyl chloride, carbon tetrachloride and methyl carbamate was 1: 1.05: 1.1,The catalyst in an amount of 5% by mass o-aminobenzoyl chloride,The amount of pyridine is 3.12 times of the molar number of o-aminobenzoyl chloride; 2) The mixture was reacted at 120 ° C and 0.3 MPa for 7 h; 3) The mixture was then warmed to 230 ° C,0.8 MPa, the reaction continued for 25 h; 4) After cooling,The insoluble matter was removed by filtration,The filtrate is then poured into water,Adding chloroform extraction,The organic phase was dried over anhydrous sodium sulphate and concentrated to give a white solid, 2,4-dichloroquinazoline, 99.1% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With palladium diacetate; caesium carbonate; XPhos; In 1,4-dioxane; at 85℃; | A mixture of <strong>[1837-55-4]3,5-dichloropyridazine</strong> (1.5 g, 10.07 mmol), methyl carbamate (0.831 g, 11.08 mmol), XANTPHOS (0.466 g, 0.805 mmol), PdOAc2 (0.226 g, 1.007 mmol) and CS2CO3 (6.56 g, 20.14 mmol) were taken in 1,4-dioxane (40 mL) and heated at 85 C overnight. The reaction mixture was concentrated, diluted with water and extracted with ethyl acetate. The ethyl acetate layer was collected, dried over Na2S04, filtered, and concentrated under reduced pressure to afford methyl (5- chloropyridazin-3-yl)carbamate (1.71 g, 9.12 mmol, 91% yield) as a brown solid. LCMS (ESI) m/e 187.9 [(M+H)+, calcd for C6H7CIN3O2 188.0]; LC/MS retention time (Method C): fa = 0.59 min. |
Yield | Reaction Conditions | Operation in experiment |
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49% | In a container having an internal volume of 300 mL equipped with a thermometer and a reflux condenser, 7.07 g (43.0 mmol) of <strong>[702-79-4]1,3-dimethyladamantane</strong>, And 24.7 g (154 mmol) of bromine were added, 60 to 70 C with stirring For 12 hours and a half. Of the 25.84 g of the obtained reaction solution, 8.81 g The reaction solution was separated. 8.81 g Of the reaction solution is heated at 20 to 30 C. , And then 7.16 g of methyl carbamate (95.4 mmol) were added, The reaction was carried out at 70 to 80 C. with stirring. After 3.5 hours, the obtained reaction solution was cooled to 5 to 10 C., then 9.6 g of dichloromethane and 24.5 g of 20% sodium sulfite aqueous solution were added and the organic layer was taken out. The obtained organic layer was sequentially washed with an aqueous solution of sodium carbonate and water, and then concentrated under reduced pressure. The obtained concentrate was purified by silica gel column chromatography (ethyl acetate: n-hexane = 5: 1 (volume ratio)) to obtain, as a white solid, 1.72 g of 1-methoxycarbonylamino-3,5-dimethyladamantane was obtained (yield: 49%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.2% | With [bis(2-(diphenylphosphino)ethyl)amino]hydrazine; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 160℃; for 12h; | 7 Example 7 0.3742 g of methyl carbamate was added to the hydrogenation reactor.0.0224 g of carbonyl chloride hydrogenated [bis (2-diphenylphosphinoethyl) amino] hydrazine, 0.0550 potassium tert-butoxide,10mL of tetrahydrofuran,Charge 6MPa hydrogen,After stirring the reaction at 160 °C for 12 hours,Stop heating and stirringCool to room temperatureSlowly release unreacted hydrogen.Take appropriate amount of reaction solution, add the internal standard, prepare the standard solution and analyze its composition by gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
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92% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-3,4-dihydronaphtho[3,4-e][1,3]oxazine-2,5,10-triones (4a-f); general procedure General procedure: A mixture of 2-hydroxy-1,4-naphthoquinone (1.0 mmol), aromatic aldehyde (1.0 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80°C for 3 h. The reaction was monitored by TLC. After reaction completion, the mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. 4-(4-Chlorophenyl)-3,4-dihydronaphtho[3,4-e][1,3]oxazine-2,5,10-trione (4a): Yellow powder; m.p. 90-92 °C; IR (KBr) (νmax cm-1): 3167 (NH), 1643 and 1682 (C=O); 1H NMR (300.1 Hz, DMSO-d6): δ 6.17 (1H, s, CH), 7.12-7.98 (8H, m, 8 ×ArH), 8.35 (1H, s, NH); 13C NMR (75.46 Hz, DMSO-d6): δ 39.1 (CH), 111.5, 125.8, 126.0, 126.4, 128.6, 131.0, 132.3, 133.6, 134.9, 138.4, 145.7, 160.0, 172.2, 181.7 and 185.1; MS m/z (%): 339 (10). Anal. calcd for C18H10ClNO4: C, 63.64; H, 2.97; N, 4.12; found: C, 63.77; H, 3.08; N, 4.25%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-3,4-dihydronaphtho[3,4-e][1,3]oxazine-2,5,10-triones (4a-f); general procedure General procedure: A mixture of 2-hydroxy-1,4-naphthoquinone (1.0 mmol), aromatic aldehyde (1.0 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80°C for 3 h. The reaction was monitored by TLC. After reaction completion, the mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-3,4-dihydronaphtho[3,4-e][1,3]oxazine-2,5,10-triones (4a-f); general procedure General procedure: A mixture of 2-hydroxy-1,4-naphthoquinone (1.0 mmol), aromatic aldehyde (1.0 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80°C for 3 h. The reaction was monitored by TLC. After reaction completion, the mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-3,4-dihydronaphtho[3,4-e][1,3]oxazine-2,5,10-triones (4a-f); general procedure General procedure: A mixture of 2-hydroxy-1,4-naphthoquinone (1.0 mmol), aromatic aldehyde (1.0 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80°C for 3 h. The reaction was monitored by TLC. After reaction completion, the mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-3,4-dihydronaphtho[3,4-e][1,3]oxazine-2,5,10-triones (4a-f); general procedure General procedure: A mixture of 2-hydroxy-1,4-naphthoquinone (1.0 mmol), aromatic aldehyde (1.0 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80°C for 3 h. The reaction was monitored by TLC. After reaction completion, the mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-3,4-dihydronaphtho[3,4-e][1,3]oxazine-2,5,10-triones (4a-f); general procedure General procedure: A mixture of 2-hydroxy-1,4-naphthoquinone (1.0 mmol), aromatic aldehyde (1.0 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL) and stirred at 80°C for 3 h. The reaction was monitored by TLC. After reaction completion, the mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-6-hydroxymethyl-1,4-dihydropyrano[3,2-e][1,3]oxazine-2,8-diones (4a-f); general procedure General procedure: A mixture of kojic acid (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-6-hydroxymethyl-1,4-dihydropyrano[3,2-e][1,3]oxazine-2,8-diones (4a-f); general procedure General procedure: A mixture of kojic acid (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-6-hydroxymethyl-1,4-dihydropyrano[3,2-e][1,3]oxazine-2,8-diones (4a-f); general procedure General procedure: A mixture of kojic acid (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. 4-(4-Chlorophenyl)-6-hydroxymethyl-1,4-dihydropyrano[3,2,e][1,3]oxazine-2,8-dione(4a): Yellow powder; m.p. 93-95 °C; IR (KBr) (νmax cm-1): 3165 (OH), 1661 (C=O); 1H NMR (300.1 Hz, DMSO-d6): δ 4.31 (2H, s, OCH2), 5.28 (1H, br s, OH), 6.12 (1H, s, CH), 6.32 (1H, s, =CH), 7.04 (2H, d, 3JHH= 8 Hz, 2CH of C6H4Cl), 7.57 (2H, d, 3JHH= 8 Hz, 2CH of C6H4Cl), 8.58 (1H, s, br, NH); 13C NMR (75.46 Hz, DMSO-d6): δ 31.1 (CH), 59.9 (OCH2), 99.9, 109.5, 125.8, 129.2, 140.5, 142.2, 142.5, 145.1, 170.8, 174.5; MS m/z (%): 307 (10). Anal. calcd for C14H10ClNO5: C, 54.65; H, 3.28; N, 4.55; found: C, 54.77; H, 3.40; N, 4.71%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With toluene-4-sulfonic acid In water at 80℃; for 3h; Green chemistry; | Synthesis of 4-aryl-6-hydroxymethyl-1,4-dihydropyrano[3,2-e][1,3]oxazine-2,8-diones (4a-f); general procedure General procedure: A mixture of kojic acid (1 mmol), aromatic aldehyde (1 mmol), methyl carbamate (1.5 mmol) and p-TSA (0.1 mmol) was suspended in water (10 mL), and stirred at 80 °C for 3 h. The reaction was monitored by TLC. After completion, the reaction mixture was allowed to cool to room temperature. The solid was collected by filtration and recrystallised from ethanol to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | A 100 mL three-necked flask was added with compound 3 (5 g, 28.05 mmoL), compound 4-a (2.3 g, 30.86 mmoL), acetic acid (2.0 g, 33.66 mmoL), 30 mL of dichloromethane, and the system was cooled to 0 C, after about half an hour. Sodium triacetoxyborohydride (8.9 g, 42.1 mmol) was slowly added and the system was reacted at room temperature for 12 h.Add 30mL of 10% NaOH solution to the system and stirThe mixture was separated and the aqueous phase was extracted twice with dichloromethane (30 mL*2). The organic phase was combined and washed with 30 mL of saturated NaCI.The solid was recrystallized from ethyl acetate / n-heptane = 1/10 to yield compound 5-a, white solid, 5.73 g, yield 86%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With trichlorophosphate In N,N-dimethyl-formamide; toluene at 80℃; for 3h; Inert atmosphere; | |
59% | With trichlorophosphate In N,N-dimethyl-formamide; toluene at 80℃; for 3h; Inert atmosphere; Cooling with ice; | 5.2.4. General procedure for the synthesis of intermediates 8a-c General procedure: To a solution of 2-cyanoacetic acid 6 (15.0 g, 176.35 mmol) andcarbamate 7a-c (176.35 mmol) in the mixed solvents of toluene(90 mL) and DMF (5.4 mL) was addedPOCl3(8.22 mL, 88.18 mmol)cooled with an ice bath. The reaction mixture was stirred at 80 Cfor 3 h under argon, then slowly poured into ice-cold water(500 mL). The precipitated solid was filtered and washed withsaturatedNH4Cland water to afford compounds 8a-c. |
58.6% | With trichlorophosphate In N,N-dimethyl-formamide; toluene at 0 - 80℃; for 3h; Inert atmosphere; | 1.1 Step 1: Preparation of (2-cyanoacetyl)carbamic acid methyl ester 2a Under Ar protection, compound 1a (15.0g, 176.35mmol), 90mL toluene, methyl carbamate (13.24g, 176.35mmol),5.4mL DMF was placed in a 250mL round bottom flask.POCI3 (8.22mL, 88.18mmol) was slowly added dropwise at 0 ° C,After the addition, the reaction temperature was raised to 80 ° C for 3 hours.The reaction was detected to be complete by TLC. The reaction liquid was decanted, and the remaining tan solid was added. 500 mL of water was added, beating, suction filtration, and infrared lamp drying, to obtain intermediate 2a, a white solid 14.64 g, yield 58.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With di-n-butyltin maleate In toluene for 3h; Reflux; | Tin-Catalyzed Transcarbamoylation Using Methyl Carbamate; Typical Procedure. Dodecyl Carbamate (13b) General procedure: A solution of dodecanol (13a; 300 mg, 1.6 mmol), methyl carbamate (480 mg, 6.4 mmol) and dibutyltin maleate (35 mg, 0.1 mmol) in toluene (13 mL) was heated at reflux for 3 h. The reaction mixture was cooled to r.t. and diluted with H2O and EtOAc. The separated aqueous layer was extracted with EtOAc and the combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product (422 mg) was purified by silica gel chromatography (1:5 EtOAc/n-hexane) to afford dodecyl carbamate (13b; 357 mg, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In toluene at 55 - 60℃; for 2.5h; | 1 The reaction of 3-trifluoromethylpyridine-2-sulfonyl chloride and above-mentioned methyl carbamate: 3-Trifluoromethylpyridine-2-sulfonyl chloride 198g (0.81mol, 1.0eq) and methyl carbamate 66.9g (0.89mol, 1.1eq) were heated to 55-60°C under 50-70mm Hg Under vacuum, keep the temperature under pressure for 2 hours, then add 400 g of toluene, stir at 55-60 °C for 0.5 hours, then cool to room temperature with stirring at room temperature, and filter to obtain 218.7 g of N-methoxycarbonyl-3-trifluoromethylpyridine-2-sulfonamide, yield 95%, 390 g of liquid obtained after filtration (mainly toluene, which can be recovered and used after distillation). |
Tags: 598-55-0 synthesis path| 598-55-0 SDS| 598-55-0 COA| 598-55-0 purity| 598-55-0 application| 598-55-0 NMR| 598-55-0 COA| 598-55-0 structure
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