Phosphorus oxychloride → Pyridine-3-sulfonyl chloride

HRID 2387646Notes

Reaction equation

HRID 2387646 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([S:7]([OH:10])(=O)=[O:8])[CH:2]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:12].P(Cl)(Cl)(Cl)=O>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([S:7]([Cl:12])(=[O:10])=[O:8])[CH:2]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 694683-Pyridinesulfonic acid

Product 1

HCID 3164136Pyridine-3-sulfonyl chloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Pyridine-3-sulfonic acid (125 g, 0.78 m) was placed in a 1 L, 3-necked flask equipped with mechanical stirrer, reflux condenser, thermometer and nitrogen inlet. Next, the phosphorus pentachloride (250 g, 1.19 m, 1.5 eq) was added, followed immediately by the phosphorus oxychloride (330 ml, 3.8 m, 4.5 eq). The contents of flask were initially stirred at ambient temperature for 30 min, then brought slowly to gentle reflux (internal temp. approx. 110° C.) over the next hour, kept at this temperature for approx. 3.5 hr then allowed over the next 12 hr to cool back to ambient temperature. Gas evolution was observed during this time. The volatiles were stripped under reduced pressure (at 12 mmHg/40° C.) and yellow semi-solid residue was diluted with DCM (1 L). The slurry was poured slowly into the stirred, ice-cold sat. aq. bicarbonate, maintaining pH=7. Gas evolution was observed. The organic layer was separated and aqueous layer was back-extracted with DCM. The combined extracts were washed with cold sat. aq. bicarbonate, brine and dried with magnesium sulfate. The solids were filtered off and filtrate evaporated, leaving pyridine-3-sulfonyl chloride as a pale yellow, oily liquid, 123 g (93% pure; 88% theory). 1H-NMR, CDCl3, (δ): 9.26 (d, 1H), 8.98 (dd, 1H), 8.34 (m, 1H), 7.62 (m, 1H). 13C-NMR, CDCl3, (δ): 155.3, 147.4, 140.9, 134.6, 124.2.

Workup

  1. customequipped with mechanical stirrer
  2. temperaturereflux condenser
  3. temperatureto gentle reflux (internal temp. approx. 110° C.) over the next hour
  4. waitkept at this temperature for approx. 3.5 hr
  5. customthen allowed over the next 12 hr
  6. temperatureto cool back to ambient temperature
  7. customwere stripped under reduced pressure (at 12 mmHg/40° C.) and yellow semi-solid residue
  8. additionThe slurry was poured slowly into the stirred, ice-cold sat. aq. bicarbonate
  9. temperaturemaintaining pH=7
  10. customThe organic layer was separated
  11. extractionaqueous layer was back-extracted with DCM
  12. washThe combined extracts were washed with cold sat. aq. bicarbonate, brine
  13. dry with materialdried with magnesium sulfate
  14. filtrationThe solids were filtered off
  15. customfiltrate evaporated

Sources & evidence

ORD record
ord-34e2beef8f2846bf8fbb6eccb87cd078
Source dataset
uspto-grants-2012_09
Patent number
US08268935B2

Reaction notes

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