* 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.
In an 1 I-three-necked flask with a drying pipe, KPG stirrer and glass stopper, 310 g polyphosphoric acid (84percent; Across Organics) were weighed in and were heated at an oil bath temperature of 75°C. Within 10 min 8.6 g (47.15 mmol) (4- methoxyphenoxy) acetic acid were added; then stirring was carried out for 40 min at 75°C. The cooled solution was poured onto 1.5 1 ice. After stirring during 2 hours, three extractions were carried out with a total of 400 mi chloroform. The combined organic phases were washed with water, 10percent K2CO3 solution and again with water and were dried over Na2SO4. After removal of the solvent in the rotation evaporator, the residue was purified by column chromatography (silica gel 60; chloroform). Thus, 774 mg (10percent) 5-methoxy-3(2H)-benzofuranone were obtained. For an alternative formula, cf. Hammond et al. ; 1990 [29].
Stage #1: With sodium hydroxide In waterCooling with ice Stage #2: for 0.333333 h; Stage #3: at 105℃; for 5 h;
General procedure: Compounds B1−7 were prepared by similar procedures. In atypical synthesis of B1, monochloroacetic acid (0.04 mol,3.78 g) was dissolved in deionized water (15 mL) under thecondition of stirring and an ice bath. Then NaOH (25 percent) wasadded dropwise until the pH value was adjusted to 9−10, thena solution of sodium chloroacetate was obtained. To a solutionof NaOH (0.03 mol, 1.20 g), deionized water (15 mL) andethanol (5 mL), phenol (0.04 mol, 3.76 g) was slowly addedunder stirring. After addition, the mixture was stirred for20 min, then the above sodium chloroacetate was addeddropwise, and heated to 105 °C and refluxed for 5 h. Thereaction mixture was cooled to room temperature. The pHvalue of the mixture was acidified to 1−2 with diluted hydrochloricacid. The precipitate was filtered, washed with dilutedhydrochloric acid many times, and recrystallized and dried invacuum, resulting in a white solid product of thephenoxyacetic acid (B1)
68%
Stage #2: With sodium hydroxide In ethanol; water at 105℃; for 5 h;
General procedure: A mixture of NaOH (0.04 mol, 1.60 g), deionized water (20 mL) and ethanol (20 mL) were poured into a 150 mL three-necked flask, then phenol (0.04 mol, 3.76 g) was slowly added under stirring. Twenty minutes later, the above sodium chloroacetate was added dropwise. The reaction solution was heated to 105 °C and refluxed for 5 h. After cooling down, the pH value of the mixture was acidified to 1-2 with diluted hydrochloric acid. The precipitate was collected by filtration and washed with diluted hydrochloric acid many times. Recrystallized and dried under a vacuum, resulting in a white solid product of the phenoxyacetic acid (4a).
Reference：
[1] Synthetic Communications, 1996, vol. 26, # 23, p. 4337 - 4341
[2] Journal of Fluorescence, 2015, vol. 25, # 4, p. 849 - 859
[3] Luminescence, 2018, vol. 33, # 5, p. 855 - 862
[4] Luminescence, 2015, vol. 30, # 5, p. 677 - 685
[5] Journal of Molecular Structure, 2014, vol. 1074, p. 487 - 495
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[8] Journal of the American Chemical Society, 1931, vol. 53, p. 304
[9] Journal of the American Chemical Society, 1943, vol. 65, p. 1555
[10] Chimica Therapeutica, 1970, vol. 5, p. 211 - 215
[11] Agricultural and Biological Chemistry, 1983, vol. 47, # 11, p. 2653 - 2656
[12] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4597 - 4601
[13] European Journal of Medicinal Chemistry, 2009, vol. 44, # 11, p. 4726 - 4733
[14] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 12, p. 3180 - 3186
[15] Phosphorus, Sulfur and Silicon and the Related Elements, 2014, vol. 189, # 9, p. 1337 - 1345
[16] Research on Chemical Intermediates, 2016, vol. 42, # 6, p. 5269 - 5280
[17] Journal of Heterocyclic Chemistry, 2016, vol. 53, # 1, p. 183 - 187
[18] Patent: CN103666452, 2016, B, . Location in patent: Paragraph 0076; 0077
3
[ 3926-62-3 ]
[ 150-76-5 ]
[ 1877-75-4 ]
Yield
Reaction Conditions
Operation in experiment
75%
Stage #1: With sodium hydroxide In ethanol; water at 20℃; for 0.333333 h; Stage #2: at 102℃; for 5 h;
General procedure: 55mmol monochloroacetic acid was dissolved in 15mL deionized water under the condition of ice water bath, then 30percent NaOH solution was used to adjust pH 8–9, sodium chloroacetate solution was obtained. 45mmol NaOH was dissolved in mixed solvent of 15mL deionized water and 5mL ethanol at room temperature with constant stirring, 45mmol phenol was subsequent slowly added. After stirring for another 20min, sodium chloroacetate solution was added. Subsequently, the mixture was refluxed at 102°C for 5h. After the mixture was cooled to room temperature, pH was adjusted to 1–2 with 2.0mol·L−1 HCl, amounts of white precipitations were gained. The precipitations were filtered and washed 3 times with dilute hydrochloric acid, dried at 60°C. White crude product was dispersed in 100mL heated deionized water, pH was adjusted to 8.0 using saturated potassium carbonate solution, then mixture solution was filtered, and filtrate was collected. White precipitated was obtained by adjusting pH of filtrate to 1–2 with 2.0mol·L−1 HCl. After cooled down to room temperature naturally, the mixture was filtered, washed with dilute hydrochloric acid, dried overnight in vacuum, then target product (b1) was obtained. The synthetic procedures of phenoxyacetic acid derivative (b2−7) were similar to that of phenoxyacetic acid (b1).
Reference：
[1] Medicinal Chemistry Research, 2010, vol. 19, # 1, p. 33 - 57
[2] Dyes and Pigments, 2018, vol. 158, p. 28 - 35
[3] Luminescence, 2014, vol. 29, # 8, p. 1113 - 1122
4
[ 18598-23-7 ]
[ 1877-75-4 ]
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[1] Journal of Materials Chemistry, 1998, vol. 8, # 4, p. 919 - 924
[2] Journal of the American Chemical Society, 1987, vol. 109, p. 5235
[3] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 23, p. 10049 - 10060
[4] British Journal of Pharmacology, 2013, vol. 170, # 4, p. 822 - 834
[5] Patent: WO2014/100730, 2014, A1, . Location in patent: Paragraph 00270
[6] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 10, p. 2526 - 2530
5
[ 150-76-5 ]
[ 1877-75-4 ]
Reference：
[1] Journal of the American Chemical Society, 1987, vol. 109, p. 5235
[2] British Journal of Pharmacology, 2013, vol. 170, # 4, p. 822 - 834
[3] Chemistry - A European Journal, 2014, vol. 20, # 18, p. 5492 - 5500
[4] Patent: WO2014/100730, 2014, A1,
[5] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 16, p. 3732 - 3735
[6] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 23, p. 5601 - 5603
[7] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 10, p. 2526 - 2530
6
[ 22446-17-9 ]
[ 1877-75-4 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 23, p. 5601 - 5603
7
[ 79704-02-2 ]
[ 1877-75-4 ]
Reference：
[1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 2, p. 154 - 156
[2] Journal of Chemical Research, 2010, # 8, p. 452 - 454
[3] Chemistry - A European Journal, 2014, vol. 20, # 18, p. 5492 - 5500
[4] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 16, p. 3732 - 3735
8
[ 96-34-4 ]
[ 150-76-5 ]
[ 1877-75-4 ]
Reference：
[1] Journal of Organic Chemistry, 2002, vol. 67, # 13, p. 4458 - 4465
9
[ 79-08-3 ]
[ 150-76-5 ]
[ 1877-75-4 ]
Reference：
[1] Journal of the Chemical Society. Perkin Transactions 2, 2001, # 9, p. 1506 - 1511
[2] International Journal of Chemical Kinetics, 2001, vol. 33, # 10, p. 612 - 616
10
[ 13794-15-5 ]
[ 1877-75-4 ]
Reference：
[1] Journal of Organic Chemistry, 2002, vol. 67, # 13, p. 4458 - 4465
11
[ 111479-08-4 ]
[ 1877-75-4 ]
Reference：
[1] Journal of Organic Chemistry, 2002, vol. 67, # 13, p. 4458 - 4465
12
[ 105-36-2 ]
[ 150-76-5 ]
[ 1877-75-4 ]
Reference：
[1] Journal of Agricultural and Food Chemistry, 2016, vol. 64, # 47, p. 8986 - 8993
Reference：
[1] Zhurnal Analiticheskoi Khimii, 1950, vol. 5, p. 7,8[2] Chem.Abstr., 1950, p. 4374
[3] Doklady Akademii Nauk SSSR, 1949, vol. 68, p. 77,79[4] Chem.Abstr., 1950, p. 1936
15
[ 1122-95-8 ]
[ 79-11-8 ]
[ 1877-75-4 ]
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1996, vol. 35, # 4, p. 333 - 338
Stage #1: chloroacetic acid With sodium hydroxide In water Cooling with ice;
Stage #2: 4-methoxy-phenol In ethanol; water for 0.333333h;
Stage #3: In ethanol; water at 105℃; for 5h;
Synthesis of Phenoxyacetic Acid Derivatives (B1-7)
General procedure: Compounds B1-7 were prepared by similar procedures. In atypical synthesis of B1, monochloroacetic acid (0.04 mol,3.78 g) was dissolved in deionized water (15 mL) under thecondition of stirring and an ice bath. Then NaOH (25 %) wasadded dropwise until the pH value was adjusted to 9-10, thena solution of sodium chloroacetate was obtained. To a solutionof NaOH (0.03 mol, 1.20 g), deionized water (15 mL) andethanol (5 mL), phenol (0.04 mol, 3.76 g) was slowly addedunder stirring. After addition, the mixture was stirred for20 min, then the above sodium chloroacetate was addeddropwise, and heated to 105 °C and refluxed for 5 h. Thereaction mixture was cooled to room temperature. The pHvalue of the mixture was acidified to 1-2 with diluted hydrochloricacid. The precipitate was filtered, washed with dilutedhydrochloric acid many times, and recrystallized and dried invacuum, resulting in a white solid product of thephenoxyacetic acid (B1)
76%
Stage #1: chloroacetic acid With sodium hydroxide In water
Stage #2: 4-methoxy-phenol With sodium hydroxide In ethanol; water at 105℃; for 5.33333h;
72%
Stage #1: chloroacetic acid With sodium hydroxide In water
Stage #2: 4-methoxy-phenol With sodium hydroxide In ethanol; water for 5h; Reflux;
68%
Stage #1: chloroacetic acid With sodium hydroxide
Stage #2: 4-methoxy-phenol With sodium hydroxide In ethanol; water at 105℃; for 5h;
Synthesis of phenoxyacetic acid derivatives (4a-h)
General procedure: A mixture of NaOH (0.04 mol, 1.60 g), deionized water (20 mL) and ethanol (20 mL) were poured into a 150 mL three-necked flask, then phenol (0.04 mol, 3.76 g) was slowly added under stirring. Twenty minutes later, the above sodium chloroacetate was added dropwise. The reaction solution was heated to 105 °C and refluxed for 5 h. After cooling down, the pH value of the mixture was acidified to 1-2 with diluted hydrochloric acid. The precipitate was collected by filtration and washed with diluted hydrochloric acid many times. Recrystallized and dried under a vacuum, resulting in a white solid product of the phenoxyacetic acid (4a).
39%
With sodium hydroxide In water for 2h; Heating;
34%
With sodium hydroxide In water at 75℃; for 3h;
With sodium hydroxide at 100℃;
With sodium hydroxide
With sodium hydroxide for 9h; Heating;
With potassium carbonate In acetone for 8h; Reflux;
With sodium hydroxide
With sodium hydroxide at 100 - 110℃;
With sodium hydroxide
With sodium hydroxide In water at 100 - 110℃;
With sodium hydroxide In water
2
0.3mol of chloroacetic acid dissolved in 60ml of water, adjusted to pH 9 with sodium hydroxide, then add 0.2mol of p-methoxy phenol, l0 ° C reflux, the compound T1,Followed by addition of thionyl chloride for chlorination reaction to obtain compound T2,Steamed to the thionyl chloride solvent to brown liquid, and then with anthranilic acid condensation reaction, obtained T3,Then PPA preheated to 130 ° C by adding T3 for the chemical reaction,The compound T4 was obtained. The T4 was reacted with thionyl chloride at 80 ° C under reflux,To obtain compound T5. Then, the purified T5 was methylated with methyl iodide in the system of sulfolane as the solvent to obtain the compound T6,T6-2 was added to a one-Using ethylene glycol ether as solvent,And N, N-bis (3-aminopropyl) methylamine at 120 ° C for 30min, and finally adding a large number of anhydrous ether, precipitate precipitation, filter drying compounds 4T7.
5 Example 5; Preparation of 1-carboxymethoxy-4-methoxythioxanthone
Concentrated sulphuric acid (120 mls) and dithiobisbenzoic acid (12.2 g) were charged to a reactor and 4-methoxyphenoxyacetic acid (25.5 g) was added over 1 to 2 hours at 10° to 15°C with cooling. After stirring for a further 1 hour at 10° to 20°C, then at 30° to 40°C for 2 hours a deep red solution was obtained. This reaction mixture was then quenched onto water (250 mls) whilst allowing the temperature to rise to ∼80°C. The quenched mixture was stirred for a further 25 minutes at ∼80°C then cooled to 40°C. The resulting precipitate was filtered and then washed with water. The resulting crude product was slurried in a mixture of water (80 mls), acetic acid (25 mls), and 2-butanone (45 mls) at reflux for 30 minutes, cooled to ambient temperature and filtered. The damp product cake was washed with a mixture of water and 2-butanone followed by water, then dried. 1-Carboxymethoxy-4-methoxythioxanthone (16.8g) was obtained in 66.4% yield. This was an orange / yellow powder, melting point 223° to 225°C.
In an 1 I-three-necked flask with a drying pipe, KPG stirrer and glass stopper, 310 g polyphosphoric acid (84%; Across Organics) were weighed in and were heated at an oil bath temperature of 75C. Within 10 min 8.6 g (47.15 mmol) (4- methoxyphenoxy) acetic acid were added; then stirring was carried out for 40 min at 75C. The cooled solution was poured onto 1.5 1 ice. After stirring during 2 hours, three extractions were carried out with a total of 400 mi chloroform. The combined organic phases were washed with water, 10% K2CO3 solution and again with water and were dried over Na2SO4. After removal of the solvent in the rotation evaporator, the residue was purified by column chromatography (silica gel 60; chloroform). Thus, 774 mg (10%) 5-methoxy-3(2H)-benzofuranone were obtained. For an alternative formula, cf. Hammond et al. ; 1990 [29].
With dmap; tetrabutylammomium bromide; trichlorophosphate Microwave irradiation; Heating;
76%
With trichlorophosphate Reflux;
4.3. Preparation of 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles (4a-g) and (5a-e)
General procedure: A mixture of 4-amino-5-(pyridin-3-yl)-4H-[1,2,4]triazole-3-thiol 3 (1 mmol) and substituted aromatic acids (1.1 mmol) inPOCl3 (5 mL) was refluxed for 6-7 h. The reaction mixture was slowly poured into crushed ice with stirring and neutralized with sodium bicarbonate. Solid material was filtered, washed with cold water, dried, and recrystallized from ethanol to afford 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 4a-g and 5a-e [25].
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane Inert atmosphere;
(S)-4-Benzyl-3-[(p-methoxyphenoxy)acetyl]oxazolidine-2-thione 11
In a 100 mL, flame dried, nitrogen purged round bottom flaskequipped with a magnetic stirrer bar (S)-4-benzyl-1,3-oxazolidine-2-thione (15.0 g, 77.9 mmol), CH2Cl2 (312 mL), 1-ethyl-3-(3-dimethylamino propyl)carbodiimide (EDC, 16.4 g, 85.5 mmol),DMAP (2.38 g, 19.5 mmol), and p-methoxyphenoxyacetic acid(14.2 g, 77.9 mmol) was added sequentially and stirred overnight.The reaction was quenched, extracted and the solvents removedin vacuo. The crude product was purified by flash column chromatography(hexanes:EtOAc, gradient: 80:20 to 65:35) to yield19.3 g (69%) of the title compound as an off-white solid
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