Structure of Sodium 2-Bromoethanesulfonate
CAS No.: 4263-52-9
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CAS No. : | 4263-52-9 |
Formula : | C2H4BrNaO3S |
M.W : | 211.01 |
SMILES Code : | BrCCS(=O)([O-])=O.[Na+] |
MDL No. : | MFCD00007530 |
InChI Key : | HNFOAHXBHLWKNF-UHFFFAOYSA-M |
Pubchem ID : | 23666797 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 28.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.58 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
-11.75 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-2.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.93 |
Solubility | 24.5 mg/ml ; 0.116 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.79 |
Solubility | 33.9 mg/ml ; 0.161 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.89 |
Solubility | 26.9 mg/ml ; 0.128 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.68 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.99 |
* 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 |
---|---|---|
55% | With sodium sulfite; In ethanol; water; for 6h;Reflux; | 1,2-Dibromomethane (6.2 mL, 72 mmol) and sodium sulfite (3 g, 24 mmol) were dissolved in a mixture of ethanol (25 mL) and distilled water (20 mL), heated for 6 h under reflux, allowed to cool, extracted three times with chloroform, dried with magnesium sulfate and concentrated under vacuum. Yield: 8.3 g (55%) colorless solid, melting point 289 C. IR (ATR): {tilde(nu)}=3600 (w), 3528 (w), 3408 (s), 2980 (w), 2946 (w), 2087 (w), 1635 (w), 1615 (s), 1435 (m), 1411 (m), 1294 (m), 1263 (w), 1202 (m), 1168 (m), 1112 (w), 1041 (s) 794 (w), 779 (w), 750 (w), 674 (w), 617 cm-1 (w). HRMS (ESI) (C2H4BrO3S-): calculated 186.9070, found 186.9070. Delta=0 mmu. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene; In N,N-dimethyl-formamide; at 150℃; for 12h; | Example 2; Preparation of TPD2; A mixture of 6-dodecanoyl-N-methyl-2-naphthylamine (3.0 g, 8.8 mmol) prepared in Example 1-(1), BrCH2CH2SO3Na (2.1 g, 10.0 mmol) and proton-sponge (2.2 g, 10.3 mmol) was stirred in DMF (50 ml) under a nitrogen atmosphere at 150 C. for 12 hours. The reaction mixture was extracted with water and dichloromethane, sufficiently washed with brine, and evaporated to remove the solvents. The residue was purified by column chromatography on silica gel using methanol/ethyl acetate (1:5) and recrystallized from chloroform to give TPD2 (1.8 g, yield: 44%). 1H-NMR (300 MHz, CDCl3): delta 8.42 (s, 1H), 7.90 (d, J=9.0 Hz, 1H), 7.89 (dd, J=9.0, 3.0 Hz, 1H), 7.62 (d, J=9.0 Hz, 1H), 7.20 (dd, J=9.0, 3.0 Hz, 1H), 6.90 (s, 1H), 3.71 (t, J=7.5 Hz, 2H), 3.08 (t, J=7.5 Hz, 2H), 3.01 (s, 3H), 2.68 (t, J=7.5 Hz, 2H), 1.61 (quin, J=7.5 Hz, 2H), 1.26 (m, 16H), 0.83 (t, J=7.5 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 64℃; | The above per-thiol (1 g), 2-bromoethane sulphonic acid sodium salt (1.42 g), cesium carbonate (2.2 g) and dimethylformamide (10 ml) were stirred and heated overnight at 64 C. Most of the solvent was evaporated under vacuum and the residue dissolved in water. Sodium bicarbonate solution (5% w/w, 5 ml) was added and the solution dialysed three times with water. This solution was evaporated to dryness and the residue dissolved in sodium bicarbonate solution (10 ml), dialysed and evaporated as before. This process was repeated, the resulting solid was dissolved in a small volume of water and the product precipitated with methanol. This was dissolved in water and evaporated to dryness giving the title compound (1.18 g). [00117] 1H NMR (D2O): delta 3.9 (m, 24H), 3.2 (m, 24H), 3.55-3.65 (m, 16H), 3.9 (m, 8H), 4.05 (m, 8H), 5.15 (s, 8H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0027] In the following procedure the term ?around? applied to a temperature corresponds to an interval of +/-5 C. around the indicated temperature. [0028] In a first reactor R is prepared a soda solution by mixing 2 L of demineralized water and 0.65 Kg of soda (1.03 equivalents). The obtained solution is made homogeneous at around 5 C. 0.388 Kg of thioacetic acid (1.08 eq) are then added to this solution while maintaining the temperature to around 5 C. 0.1 L of demineralized water is used to rinse the addition funnel containing thioacetic acid and is also added to the reaction mixture. Reactor R is then heated at around 20 C. and stirred at this temperature for 30 min. [0029] In a second reactor R' is placed 1 Kg of sodium bromoethanesulfonate (1.16 eq). To this reactor is added the content of reactor R. Reactor R is rinsed with 0.1 L of demineralized water and the resulting rinsing water is added to reactor R'. Reactor R' is heated to around 80 C. and stirred at this temperature for around 1 h30. The end of the reaction is monitored by HPLC. The solution is then cooled at around 50 C. [0030] In another reactor is prepared a soda solution by mixing 2 L of demineralized water and 1.36 Kg of soda. The obtained solution is made homogeneous at around 20 C. This resulting solution is added in reactor R' yielding an exothermic reaction. The resulting reaction mixture is stirred for around 30 min. . The end of the reaction is monitored by HPLC. The solution is then brought to around 55 C. [0031] In another different reactor, a solution of acetic acid is prepared by mixing 0.3 L of demineralized water and 0.3 L of acetic acid. This solution is added to reactor R'. Once pH is controlled to be in the range of 7.0-7.2 oxygen is bubbled into the reaction mixture while the temperature of the obtained mixture is maintained at around 55 C. After 8 h of bubbling, pH is checked again and the end of the reaction is monitored by HPLC (if conversion is not complete, oxygen bubbling is continued at a temperature of around 55 C. as long as needed). The reaction mixture is then filtrated on a filter of 1 mum diameter holes. [0032] Ethanol is then added to the filtrated mixture in equal volume and the resulting mixture is thoroughly stirred. Precipitates are eventually forming, which are dissolved by heating at around 65 C. The mixture is then progressively cooled to around 20 C. and may be left standing overnight at this temperature. The resulting mixture is then cooled down to around 5 C. and maintained at this temperature for 1 h. The suspension is then filtrated. [0033] In another reactor is prepared an ethanolic solution by mixing 0.1875 L of demineralized water and 0.5625 L of ethanol. This solution made homogeneous at 20 C. is used to wash the resulting ?cake? obtained from the previous suspension. The ?cake? is washed another time with 0.75 L of ethanol and the solid is dried in a ventilated oven at 60 C. until NMR displays no more ethanol. 0.70 Kg of dimesna are then obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | In 1,4-dioxane; water; at 42 - 60℃; for 48h; | A solution OF 2-BROMOETHANESULFONIC acid, sodium salt (4.2 g, 20 mmol) in water (total 12 ML) was added over 6 hours to a 42 C solution oft-butylamine (10 mL, 94 mmol) in a mixture of water (10 mL) and 1,4-dioxane (10 mL). The mixture was stirred at 42 FOR 18 hours. The mixture was then heated to 60 C for 24h. By proton NMR, 30 % of elimination product (vinylsulfonic acid) was observed. The mixture was concentrated to dryness and treated with ethanol at refluxing temperature. The solid material was collected (crop 1). The mother liquor was concentrated to dryness and the solid was again treated with ethanol at refluxing temperature, and the solid material was collected (crop 2). Both crops of the solid material were dissolved in water, and the resultant aqueous solutions passed in sequence through a Dowex 50 W X 8 ion- exchange column (100 g resin). The fractions containing the title compound were collected and concentrated to dryness. The solid material obtained was recrystallized from a mixture of ethanol (20 mL) and water (2 mL). The crystals were collected by filtration, dried in a vacuum oven at 60 C for 18 hours. Compound DU was obtained as fine white needles (860 mg, 24 % YIELD). 1H NMR (500 MHz, D20) B 1.16 (s, 9H), 3.02 (t, J= 6. 8 Hz, 2H), 3.19 (t, J= 6. 8 Hz, 2H). 13C NMR (125 MHz, D20) 8 24. 8, 37. 3,47. 0,57. 8. ES-MS 182 (M+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; In water;Heating / reflux; | EXAMPLE 1 Production of Sodium 2-bromoethane Sulfonate After 1018 g of 47% hydrobromic acid were added dropwise to 292 g of 60% aqueous sodium isethionate solution, the mixture was heated under reflux and 348 g were distilled off at normal pressure. The residue was cooled to 50 C. and 252 g of 47% hydrobromic acid were added, then further cooled from 50 C. to 5 C. The precipitated crystals were filtered out at about 5 C. and washed with 77.1 g of 47% hydrobromic acid being cooled to about 5 C. and then 17.5 g of water being cooled to about 5 C. The crystals were washed twice with a mixture of 408.6 g of acetone and 47.4 g of water being cooled to about 5 C., and further washed twice with 221 g of acetone being cooled to about 5 C. The crystals were dried under reduced pressure to afford 120 g of sodium 2-bromoethane sulfonate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 2 Production of Disodium 2,2'-dithiobis Ethane Sulfonate To a mixture of 50.1 g of water with 24.4 g of thioacetic acid, 50.7 g of 25% aqueous sodium hydroxide solution were added dropwise at 10-30 C. This solution was added dropwise to a solution of 63.3 g of sodium 2-bromoethane sulfonate and 70 g of water at 50-70 C. and allowed to react at 80-90 C. for 2 hours. Thereto 54.2 g of 25% aqueous sodium hydroxide solution were added and allowed to react at refluxing temperature (about 105 C.) until the end of the reaction was confirmed by HPLC. After addition of 3.25 g of acetic acid, the reaction mixture was refluxed for 6 hours and then cooled to about 30 C. The pH of the mixture was adjusted to 7.3 with 25% sodium hydroxide solution. Oxygen was allowed to react with 260 mL of aqueous sodium 2-mercapto ethane sulfonate solution obtained above at about 30 C. and 0.5-0.6 MPa of oxygen pressure. When the end of the reaction was confirmed by HPLC, the reaction was stopped and the mixture was neutralized with acetic acid. The mixture was heated to about 70 C. and it was observed that the mixture had been dissolved. After that, the mixture was filtered with a filtering assistant agent (radiolite) and the filtering assistant agent was washed with 10 g of water. The mixture was concentrated under reduced pressure (about 10 kPa) at 70 C. When the amount of the distilled out water became 60 g, the concentration was stopped and it was observed that the mixture remained dissolved at about 75 C. Cooling the mixture, crystallization began at 60+-5 C. After aging for about 30 minutes, the mixture was cooled to 25 C. and the crystals were aged for 2 hours at 25 C. The crystals were filtered out and washed with 24 g of water being cooled to 2 C. and then 48 mL of 70% aqueous ethanol solution. Drying the crystals at about 70 C. afforded 39.1 g of substantially pure disodium 2,2'-dithiobis ethane sulfonate crystals. The yield was 77.6% after crystallization. The purity of the product was 99.4%. According to the present invention, compounds of Formula II, such as disodium 2,2'-dithiobis ethane sulfonate, can be produced by an efficient procedure from available, relatively less expensive raw compounds in good yield with high purity. The above details are not limitative of the invention, which is defined by the scope of the following claims. It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the appended claims. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In methanol; ethanol; water; ethyl acetate; | (a) Sodium 2-[{2-(1,3-benzodioxol-5-yl)ethyl}thio]-ethanesulfonate STR258 15 g of 2-(1,3-benzodioxol-5-yl)ethanethiol and 17.4 g of sodium 2-bromoethanesulfonate were dissolved in a mixture of 280 ml of ethanol and 120 ml of water. 3.3 g of sodium hydroxide was added to the solution and the mixture was heated under reflux for 1 h. The reaction mixture was concentrated and 500 ml of ethyl acetate and 500 ml of water were added thereto. After separation of the layers, the aqueous layer was acidified with hydrochloric acid. After extraction with n-butanol, the extract was washed with a saturated aqueous common salt solution. The solvent was distilled off to obtain 19 g of a faint yellow residue. This product was dissolved in a solution of 2.94 g of sodium hydroxide in dilute methanol and recrystallized therefrom to obtain 14.7 g of the intended compound in the form of colorless crystals. 1 H-NMR (90MHz, DMSO-d6) delta;2.72 (s,8H), |