3-Amino-1-propanol → Xylazine

HRID 2249228Notes

Reaction equation

HRID 2249228 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4]O.[CH3:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[C:8]=1[N:14]=[C:15]=[S:16]>O1CCCC1>[CH3:13][C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([CH3:6])[C:8]=1[NH:14][C:15]1[S:16][CH2:4][CH2:3][CH2:2][N:1]=1

Participants

4

Reactant 2

HCID 90863-Amino-1-propanolHCID 879762,6-Xylyl isothiocyanate

Product 1

HCID 5707XylazineYield 74.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

380 ml (373 grams, 4.97 moles) of 3-amino-1-propanol and 450 ml of tetrahydrofuran ("THF") were added to a 5-L flask fitted with a mechanical stirrer, teflon clad thermol-couple and an addition funnel. Then with rapid stirring, 749 grams (4.59 moles) of the 2,6-dimethylphenylisothiocyanate were added dropwise over a 2 hour period. The temperature was kept below 45° C. by controlling the rate of addition and by the use of a cooling bath. The cooling bath was removed, and replaced with a heating mantle. The temperature was raised to 50° C. followed by the addition of 435 ml. concentrated hydrochloric acid. The addition funnel was removed and a distillation head was placed on the flask. Heating was continued with the distillation of THF and water until the internal temperature had reached 95° C., which took about 2 hours. The reaction mixture was then diluted with 2 liters of water and the stirred solution was allowed to cool to room temperature. The aqueous solution was filtered through a 0.2 microfilter. The reaction mixture was made basic by the careful addition of 10% sodium hydroxide. The addition was continued until the pH of the solution was greater than or equal to 12. A solid was collected by filtration, washed with water and partially dryed in the funnel. The solid was then transferred into a flask fitted with a mechanical stirrer and 1 liter of acetone was added. The slurry was stirred for 1 hour using an ice bath to chill the mixture. The product was isolated by filtration, and air dryed to give 750 grams of crude xylazine. The product had a purity of 99% by GC analysis and gave a IR spectrum that was virtually identical to that of a standard sample of xylazine. The 80 MHz 1HNMR spectrum (CDCl3) produced the following results: delta 7.15 (bs, 3, ArH), 4.5 (t, 2, CH2), 3.15 (t, 2, CH2), 2.9-2.0 (m, 8, CH2 and CH3) was in complete agreement with a spectrum of a standard xylazine sample. Furthermore, the mixed melting point of the xylazine sample and a standard showed no depression.

Workup

  1. customfitted with a mechanical stirrer
  2. customwas kept below 45° C.
  3. additionthe rate of addition
  4. customThe cooling bath was removed
  5. additionfollowed by the addition of 435 ml
  6. customThe addition funnel was removed
  7. temperatureHeating
  8. distillationwas continued with the distillation of THF and water until the internal temperature
  9. customhad reached 95° C.
  10. additionThe reaction mixture was then diluted with 2 liters of water
  11. temperatureto cool to room temperature
  12. filtrationThe aqueous solution was filtered through a 0.2 microfilter
  13. additionThe reaction mixture was made basic by the careful addition of 10% sodium hydroxide
  14. additionThe addition
  15. filtrationA solid was collected by filtration
  16. washwashed with water
  17. customThe solid was then transferred into a flask
  18. customfitted with a mechanical stirrer
  19. addition1 liter of acetone was added
  20. temperatureto chill the mixture
  21. customThe product was isolated by filtration, and air

Sources & evidence

ORD record
ord-8fc192c1eb7a4266a40f904b2439f6a4
Source dataset
uspto-grants-1991_08
Patent number
US05043442

Reaction notes

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