Structure of 27563-65-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 27563-65-1 |
Formula : | C8H5ClO4 |
M.W : | 200.58 |
SMILES Code : | O=C(O)C1=CC=CC(Cl)=C1C(O)=O |
MDL No. : | MFCD00100580 |
InChI Key : | BKFXSOCDAQACQM-UHFFFAOYSA-N |
Pubchem ID : | 96254 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
A 45.85 g sample of an oxidation mixture in acetic acid from the oxidation of 3- and 4-chloroxylene in the presence of a catalyst composition comprising cobalt and manganese was treated with 0.143 g. of oxalic acid dihydrate and brought to reflux for 30 minutes (this process removed about 90% of the cobalt and >50% of the manganese by precipitation as the oxalate salts). The solution was then passed through a glass frit under vacuum. The remainder of the solvent was removed by evaporation (down to 16.2 g.) and distillation (down to 14.0 g. residue). The remaining light yellow solid was combined with 60 ml. of water and 40 ml. of toluene, and mixed. There was some emulsion layer which was treated in a second wash with an additional 15 ml. each of water and toluene. The solvent was removed by evaporation of each fraction to leave 10.6 g. in the water fraction and 2.7 g. in the toluene fraction. The fractions were analyzed by GC. The analytical results are shown in Table 7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; at 60℃; for 2h; | A 35 wt. % solution of crude chlorophthalic acid in water was prepared by adding appropriate amounts of 4- and 3-chlorophthalic anhydride (70/30 isomer ratio) along with a mixture of about 3 wt. % (based on crude chlorophthalic anhydride) of synthetic 4- and 7-chlorophthalide (produced by reduction of 3-chlorophthalic anhydride). This mixture was stirred at approximately 60 C. for 2 hours after which all of the chlorophthalic anhydride had hydrolyzed to chlorophthalic acid as shown by gas chromatographic (GC) analysis which showed no anhydride in the extracted organic phase. A number of vials were prepared each containing 5 milliliters (ml.) of an aqueous phase comprising a certain concentration of crude chlorophthalic acid (5 wt. % to 35 wt. %, based on the weight of the entire aqueous phase and, optionally, acetic acid (0 wt. % to 36 wt. %, based on the weight of the entire aqueous phase). Each vial was then treated with 5 ml. of either toluene, o-dichlorobenzene (ODCB), or ortho-xylene. The vials were then shaken vigorously in a mechanical shaker for 50 minutes at a specified temperature (22 C., 42 C., or 60 C.). The phases were allowed to separate over several hours (actual phase separation occurred much quicker than this) and then each phase was sampled using a pipette. No stable emulsions were observed under the conditions which were examined. The organic phase was analyzed directly by GC (using biphenyl internal standard, following silylation of the product mixture), while for the aqueous phase, water was evaporated and solid residue was redissolved in organic solvent before GC analysis. The analytical data were used to calculate an equilibrium constant, K, which represented the ratio of chlorophthalides mass fraction in the organic phase to that in the aqueous phase. The analytical data were also used to calculate a selectivity constant, beta, which represented the quotient of [(wt. fraction of chlorophthalides in xylene)/(wt fraction of chlorophthalic acids in xylene)] divided by the quotient of [(wt fraction of chlorophthalides in water)/(wt fraction of chlorophthalic acids in water)]. The data in Table 1 show results of extractions performed at 22 C. with no acetic acid present. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen; In acetic acid; xylene; at 35 - 40℃;Purification / work up; | Other experiments were carried out on actual oxidation mixtures from reactions of 3- and 4-chloroxylene with oxygen in acetic acid in the presence of a catalyst. In some cases the catalyst components were removed by precipitation, for example with oxalic acid, but the low levels of metals present in those samples still containing catalyst components did not affect the solubility characteristics of the organic species. At least a portion of oxidation reaction mixture was distilled in vacuo to remove acetic acid, leaving a solid residue which was dissolved in water. The extraction of a 30 wt. percent aqueous solution of 3- and 4-chloroxylene oxidation mixture was carried out with xylene. Six extractions were made starting with 130 kilograms (kg.) of solution extracting the aqueous phase with 155 kg. of xylene. At the beginning the temperature was approximately 35 C., and later was raised to 40 C. to present the crystallization of chlorophthalic acid. The results of extraction are shown Table 5. Unless noted, the values in the table represent relative percentages in the composition of the designated components (total percentage equals 100percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic anhydride; at 122 - 136℃; for 2h;Product distribution / selectivity; | Example 2a (Cyclization Procedure Using Acetic Anhydride) The crude reaction product of Example 2 was divided into two identical fractions each weighing 1355 grams. One of the two fractions was subjected to distillation at atmospheric pressure (pot temperature 150 C.) until a total of about 952.9 grams of a mixture of water and acetic acid had been collected in the receiving vessel. The maximum head temperature was 122 C. When the head temperature reached 122 C. acetic anhydride (196.5 g, 1.93 mole) was added dropwise to the distillation flask and the resultant blue solution (no precipitate was observed) was heated at reflux (136 C.) for a two hour period. A mixture of acetic acid and acetic anhydride (198.6 grams) was then distilled off at atmospheric pressure (pot temperature 160 C.). Thereafter, vacuum was carefully applied to remove any remaining acetic anhydride, and the product chlorophthalic anhydride was distilled under vacuum. Two fractions were collected, the first distilled at 70-98 C. at a pressure in a range between 18 and 645 mbar. The first fraction (81.2 grams) contained residual acetic acid, acetic anhydride and product chlorophthalic anhydride. The second fraction distilled at between 136 and 144 C. at a pressure in a range between 3 and 5 mbar. The second fraction distilled at between 136 and 144 C. at a pressure in a range between 3 and 5 mbar. The second fraction consisted essentially of a mixture of 3- and 4-chlorophthalic anhydride (276.6 g, 1.52 mole, 86.6% of theory). Examples 3a-14a were carried out as described for Example 2. Data are gathered in Table 2. | |
at 175℃; under 60.006 Torr; for 3h;Product distribution / selectivity; | The crude reaction product of Example 14 was sampled for analysis and then divided into two identical fractions (fractions ?a? and ?b?) each weighing 1351 grams. Fraction ?b? was charged to a 2-liter flask. Distillation was carried out at atmospheric pressure (maximum pot temperature 175 C.) until a total of about 1012.8 grams of distillate had been removed. Vacuum was then carefully applied until a pressure of about 80 mbar was achieved and the mixture was heated under vacuum for about 3 hours at 175 C. to effect ring closure and water removal. The crude anhydride was vacuum distilled to afford purified chlorophthalic anhydride (282.6 g, 88.5%) as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen; acetic acid;cobalt(II) acetate; manganese(II) acetate; sodium bromide; at 152 - 190℃; under 14251.4 Torr; for 0.5 - 2h;Product distribution / selectivity; | A 3.5 liter reaction vessel equipped as described above was charged with a 95:5 mixture of 4-chloro-o-xylene and 3-chloro-o-xylene (492.1 g, 3.50 mol), acetic acid (1925 mL, 32.06 mol), cobaltous acetate tetrahydrate (13.1 g, 0.0526 mol, 1.50 mole % based on 3.5 moles of 3- and 4-chloro-o-xylene), manganous acetate tetrahydrate (6.4 g, 0.0261 mol, 0.75 mole % based on 3.5 moles of 3- and 4-chloro-o-xylene), sodium bromide (0.6 g, 0.0060 mol, 0.17 mole % based on 3.5 moles of 3- and 4-chloro-o-xylene), and sodium acetate (2.9 g, 0.0354 mol, 1.01 mole % based on 3.5 moles of 3- and 4-chloro-o-xylene). The reaction vessel was sealed and pressurized with nitrogen to 19 bar and then heated to about 160 C. Compressed air was then introduced into the reaction mixture at a rate such that the concentration of oxygen in the gas emerging from the reactor gas outlet valve was about 0.5%. The reaction temperature was maintained at about 160 C. for 1 hour and was then raised to about 175 C. and was maintained at that temperature until ?oxygen breakthrough? was noted. Oxygen breakthrough marked the beginning of the post-oxidation phase of the reaction. The compressed air being fed to the reactor was then diluted with sufficient nitrogen to limit the concentration of oxygen in the gas emerging from the reactor gas outlet valve to less than about 2% . The reaction temperature was raised to about 190 C. and maintained at that temperature throughout the post-oxidation phase which lasted approximately three hours. The reaction mixture was then assayed by HPLC and GC and found to contain the product diacids as a mixture of 3-chlorophthalic acid and 4-chlrorophthalic acid containing less than 10,000 ppm chlorobenzoic acids. Conversion of starting material to products was in excess of 90 percent. Examples 2-14 Data for a series of oxidation reactions conducted as described in Example 1 together with modifications to reaction parameters indicated are gathered in Table 1. The data demonstrate the effectiveness of the method of the present invention to produce high yields of chlorophthalic acid while limiting the amount of chlorobenzoic acid by-products. In Table 1 the header ?Variation? refers to the reaction parameter being varied in the Example, ?standard? refers to the amounts of reagents and reaction conditions used in Example 2 which are given below. 19 barabs nitrogen pressure, stirrer speed 800 rpm. Temperature 152 C. at initial oxygen introduction. Cooling begun immediately upon reaction initiation to maintain an internal temperature of about 160 C. After 60 min the temperature was raised to 175 C. At the beginning of the post-oxidation phase of the reaction the temperature was raised to 190 C for a period of 60 minutes. Still referring to Table 1, the term ?air input? refers to the variation in which the reaction was ?oxygen limited? meaning that the gas flow rate was initially 900 l/h (scaled value 180 l/h), much slower at the end of the reaction (?EOR?). The heading ?Oxidation Conds.? refers to the conditions employed in the oxidation reaction which were either (1) the ?standard? conditions as given for Example 2 or the ?oxygen limited? reaction conditions of Examples 4 and 5. The heading ?Post-Oxidation Conds.? refers to the duration (time) and temperature of the reaction following ?oxygen breakthrough?. The heading ?Cl-phthalic acid? refers to the total amount of 3- and 4-chlorophthalic acid present in the crude product mixture at the end of the oxidation reaction. The values given in the column headed ?Cl-phthalic acid? are the combined ?area percent? of the peaks attributed to 3- and 4-chlorophthalic acid in a gas chromatogram of the crude product mixture. The heading ?Isomeric CIBA's? refers to the total amount of 2-, 3-, and 4-chlorobenzoic acids present in the crude reaction mixture and expressed in parts per million (ppm). 2-chlorobenzoic acid, 3-chlorobenzoic acid, and 4-chlorobenzoic acid are believed to arise by decarboxylation of 3-chlorophthalic acid and 4-chlorophthalic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chlorine; In water; for 3h; | The phthalic acid (1mmol) dissolved in 20 ml of acid in the aqueous solution, the stirring 1.5 hours later, into the chlorine gas, reaction 3 hours, all the solvent is pumped, by adding ethyl acetate 50 ml, the resulting solution with saturated salt water washing 3 times, the organic phase after separation, the aqueous phase is extracted with twice ethyl acetate (50 ml). The combined organic phase, drying agent, filtration of the drying agent, the solvent evaporation to dryness, to obtain the corresponding ortho and meta-substituted phthalic acid chloride (yield 100%, GC purity (two isomers) 99%). |