Methane → HCID 13043971, compound

HRID 1701906Notes

Reaction equation

HRID 1701906 reaction equation
C([Li])CCC.[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]2[CH2:16][CH2:15][CH2:14][S:13]2)[N:7]=1.[CH3:17][N:18]=[C:19]=[S:20].C>CCCCCC.C(O)C.C(OCC)(=O)C.O.O1CCCC1.CN(P(N(C)C)(N(C)C)=O)C>[CH3:17][NH:18][C:19]([C:12]1([C:8]2[N:7]=[N:6][CH:11]=[CH:10][CH:9]=2)[CH2:16][CH2:15][CH2:14][S:13]1)=[S:20]

Participants

11

Reactant 4

HCID 297MethaneHCID 11167Methyl isothiocyanateHCID 13720667HCID 13720667, compoundHCID 178418339Butyllithium

Product 1

HCID 13043971HCID 13043971, compoundYield 5.7%

Reagents, catalysts & solvents 6

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolvent3×

Conditions

Temperature
0 °C

Procedure

A mixture of anhydrous hexamethylphosphorotriamide and anhydrous tetrahydrofuran (47/53 by volume; 36 cc) is added dropwise and in the course of 15 minutes to a 1.6 M solution of n-butyllithium in hexane (55 cc), kept under a nitrogen atmosphere and at a temperature of about -60° C. A solution of 2-(pyridazin-3-yl)-tetrahydrothiophen (9.7 g) in a mixture of anhydrous hexamethylphosphorotriamide and anhydrous tetrahydrofuran (47/53 by volume; 36 cc) is then added in the course of 20 minutes. After stirring for 15 minutes at the same temperature, a solution of methyl isothiocyanate (6.4 g) in a mixture of anhydrous hexamethylphosphorotriamide and anhydrous tetrahydrofuran (47/53 by volume; 36 cc) is added in the course of 15 minutes. The reaction mixture is subsequently stirred for 1 hour at -65° C. and then for one hour whilst allowing the temperature to rise gradually to -10° C. It is then run into a mixture of distilled water (350 cc) and ethyl acetate (300 cc). After decantation, the aqueous solution is extracted with ethyl acetate (200 cc). The organic extracts are combined, washed three times with distilled water (900 cc in total), dried over anhydrous sodium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 55° C. The product obtained (12.4 g) is combined with a product (1 g) prepared under the same conditions, and the combined product is chromatographed on neutral silica gel (154 g) contained in a column of diameter 3.2 cm. The column is eluted with a cyclohexane/ethyl acetate mixture (90/10 by volume; 500 cc), a cyclohexane/ethyl acetate mixture (80/20 by volume; 1000 cc), a cyclohexane/ethyl acetate mixture (70/30 by volume; 2250 cc) and a cyclohexane/ethyl acetate mixture (50/50 by volume; 2500 cc), 250 cc fractions being collected. Fractions 19 to 25 are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 55° C. The product obtained (2.4 g) is dissolved in boiling ethanol (50 cc); decolourising charcoal (0.15 g) is added to the solution, which is filtered hot, and the filtrate is then cooled for 30 minutes at 0° C. The resulting crystals are filtered off, washed with ethanol (2 cc) and then twice with diisopropyl ether (6 cc in total) and dried under reduced pressure (1 mm Hg; 0.13 kPa) at 60° C. N-Methyl-2-(pyridazin-3-yl)-tetrahydrothiophen-2-carbothioamide (0.8 g), melting at 199° C., is thus obtained.

Workup

  1. customkept under a nitrogen atmosphere and at a temperature of about -60° C
  2. additionis then added in the course of 20 minutes
  3. additionis added in the course of 15 minutes
  4. stirringThe reaction mixture is subsequently stirred for 1 hour at -65° C.
  5. waitfor one hour whilst allowing
  6. customto rise gradually to -10° C
  7. extractionAfter decantation, the aqueous solution is extracted with ethyl acetate (200 cc)
  8. washwashed three times with distilled water (900 cc in total)
  9. dry with materialdried over anhydrous sodium sulphate
  10. filtrationfiltered
  11. concentrationthe filtrate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 55° C
  12. customThe product obtained (12.4 g)
  13. customprepared under the same conditions
  14. customthe combined product is chromatographed on neutral silica gel (154 g)
  15. washThe column is eluted with a cyclohexane/ethyl acetate mixture (90/10 by volume; 500 cc)
  16. customa cyclohexane/ethyl acetate mixture (80/20 by volume; 1000 cc), a cyclohexane/ethyl acetate mixture (70/30 by volume; 2250 cc) and a cyclohexane/ethyl acetate mixture (50/50 by volume; 2500 cc), 250 cc fractions being collected
  17. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 55° C
  18. customThe product obtained (2.4 g)
  19. dissolutionis dissolved
  20. filtrationis filtered hot
  21. filtrationThe resulting crystals are filtered off
  22. washwashed with ethanol (2 cc)
  23. dry with materialtwice with diisopropyl ether (6 cc in total) and dried under reduced pressure (1 mm Hg; 0.13 kPa) at 60° C

Sources & evidence

ORD record
ord-125c14a82cdc46e6b699ffb70c0c0fd3
Source dataset
uspto-grants-1983_04
Patent number
US04379154

Reaction notes

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