Methane → HCID 13043969, compound

HRID 1701900Notes

Reaction equation

HRID 1701900 reaction equation
C([Li])CCC.[N:6]1[CH:11]=[CH:10][N:9]=[CH:8][C:7]=1[CH:12]1[CH2:16][CH2:15][CH2:14][S:13]1.[CH3:17][N:18]=[C:19]=[S:20].C>CCCCCC.C(O)CC.C(OC(C)C)(C)C.C(OCC)(=O)C.O1CCCC1.CN(P(N(C)C)(N(C)C)=O)C>[CH3:17][NH:18][C:19]([C:12]1([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][N:6]=2)[CH2:16][CH2:15][CH2:14][S:13]1)=[S:20]

Participants

11

Reactant 4

HCID 297MethaneHCID 11167Methyl isothiocyanateHCID 13720668HCID 13720668, compoundHCID 178418339Butyllithium

Product 1

HCID 13043969HCID 13043969, compoundYield 17.5%

Reagents, catalysts & solvents 6

HCID 10311-PropanolSolventHCID 7914Diisopropyl EtherSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolvent3×

Conditions

Temperature
5 °C

Procedure

A mixture of anhydrous hexamethylphosphorotriamide and anhydrous tetrahydrofuran (47/53 by volume; 70 cc) is added dropwise and in the course of 15 minutes to a 1.6 M solution of n-butyllithium in hexane (119 cc), kept under a nitrogen atmosphere and at a temperature of about -60° C. A solution of 2-pyrazinyltetrahydrothiophen (19.5 g) in a mixture of anhydrous hexamethylphosphorotriamide and anhydrous tetrahydrofuran (47/53 by volume; 70 cc) is then added in the course of 15 minutes. After stirring for 15 minutes, a solution of methyl isothiocyanate (12.7 g) in a mixture of anhydrous hexamethylphosphorotriamide and anhydrous tetrahydrofuran (47/53 by volume; 30 cc) is added in the course of 15 minutes. The reaction mixture is subsequently stirred for 45 minutes at -65° C. and then for 1 hour whilst allowing the temperature to rise gradually to about 20° C. It is then run into a mixture of ethyl acetate (300 cc) and distilled water (500 cc). After decantation, the aqueous solution is extracted twice with ethyl acetate (400 cc in total). The organic extracts are combined, washed three times with distilled water (1500 cc in total), dried over anhydrous sodium sulphate and filtered and the filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 70° C. The product obtained (33.3 g) is chromatographed on neutral silica gel (330 g) contained in a column of diameter 4.2 cm. Elution is carried out successively with a cyclohexane/ethyl acetate mixture (90/10 by volume; 4000 cc) and then with a cyclohexane/ethyl acetate mixture (80/20 by volume; 7000 cc), 500 cc fractions being collected. Fractions 13 to 22 are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 60° C. The product obtained (11 g) is dissolved in a boiling mixture of propanol and diisopropyl ether (75/25 by volume; 48 cc); decolourising charcoal (0.2 g) is added to the solution, which is filtered hot, and the filtrate is then cooled for 18 hours at 5° C. The resulting crystals are filtered off, washed with a propanol/diisopropyl ether mixture (75/25 by volume; 10 cc) and dried under reduced pressure (1 mm Hg; 0.13 kPa) at 45° C. N-Methyl-2-pyrazinyltetrahydrothiophen-2-carbothioamide (4.9 g), melting at 127° 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 15 minutes
  3. additionis added in the course of 15 minutes
  4. stirringThe reaction mixture is subsequently stirred for 45 minutes at -65° C.
  5. waitfor 1 hour whilst allowing
  6. customto rise gradually to about 20° C
  7. distillationdistilled water (500 cc)
  8. extractionAfter decantation, the aqueous solution is extracted twice with ethyl acetate (400 cc in total)
  9. washwashed three times with distilled water (1500 cc in total)
  10. dry with materialdried over anhydrous sodium sulphate
  11. filtrationfiltered
  12. concentrationthe filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 70° C
  13. customThe product obtained (33.3 g)
  14. customis chromatographed on neutral silica gel (330 g)
  15. washElution
  16. customwith a cyclohexane/ethyl acetate mixture (80/20 by volume; 7000 cc), 500 cc fractions being collected
  17. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 60° C
  18. customThe product obtained (11 g)
  19. filtrationis filtered hot
  20. filtrationThe resulting crystals are filtered off
  21. washwashed with a propanol/diisopropyl ether mixture (75/25 by volume; 10 cc)
  22. customdried under reduced pressure (1 mm Hg; 0.13 kPa) at 45° C

Sources & evidence

ORD record
ord-c5b0f72f126c4dc2af4f7161e88a74e6
Source dataset
uspto-grants-1983_04
Patent number
US04379154

Reaction notes

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