Nitric Acid → O-methyl-N-(2-chloro-5-thiazolylmethyl)-N'-nitroisourea

HRID 1386662Notes

Reaction equation

HRID 1386662 reaction equation
[NH2:1][C:2]([NH2:4])=[O:3].S(OC)(O[CH3:9])(=O)=O.S(=O)(=O)(O)O.[N+:17]([O-:20])(O)=[O:18].N[CH2:22][C:23]1[S:27][C:26]([Cl:28])=[N:25][CH:24]=1.[OH-].[Na+]>>[CH3:9][O:3][C:2](=[N:4][N+:17]([O-:20])=[O:18])[NH:1][CH2:22][C:23]1[S:27][C:26]([Cl:28])=[N:25][CH:24]=1

Participants

7

Reactant 6

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 1176UreaHCID 6497Dimethyl SulfateHCID 14798Sodium HydroxideHCID 101541292-Chloro-5-aminomethylthiazole

Product 1

HCID 136404632O-methyl-N-(2-chloro-5-thiazolylmethyl)-N'-nitroisoureaYield 64.4%

Procedure

Urea [99%] (3.03 g, 0.05 mol) and dimethyl sulfate [95%](6.64 g, 0.05 mol) were mixed at room temperature and stirred for a few minutes. The mixture was heated in an oil bath and stirred at 80° C. for 15 hours. The mixture was cooled to room temperature and sulfuric acid [95%, d 1.84] (11.2 ml, 0.2 mol) was added, and then the mixture was further cooled to 5° C. Fuming nitric acid [97%, d 1.52] (6.4 ml, 0.15 mol) was added dropwise over 25 minutes while maintaining the interior temperature to below 10° C. Then, the ice bath was removed and the temperature was gradually raised to room temperature. After stirring for total 2 hours, the mixture was poured into ice-water (60 g-40 g) and neutralized (about pH 2) by adding an aqueous 40% sodium hydroxide solution. 5-(Aminomethyl)-2-chlorothiazole (3.34 g, 0.023 mol) was added (pH 3.8) and then the pH was adjusted to about 6.7 with 40% aqueous sodium hydroxide solution, and then the mixture was stirred at room temperature for 20 hours. The deposited crystal was collected by filtration, washed and then dried to obtain 3.63 g of O-methyl-N-(2-chloro-5-thiazolylmethyl)-N′-nitroisourea. The yield was 64.4%. based on 5-(aminomethyl)-2-chlorothiazole, and 29.0% based on urea.

Workup

  1. temperatureThe mixture was heated in an oil bath
  2. stirringstirred at 80° C. for 15 hours
  3. temperaturethe mixture was further cooled to 5° C
  4. temperaturewhile maintaining the interior temperature to below 10° C
  5. customThen, the ice bath was removed
  6. temperaturethe temperature was gradually raised to room temperature
  7. stirringAfter stirring for total 2 hours
  8. additionthe mixture was poured into ice-water (60 g-40 g) and neutralized (about pH 2)
  9. additionby adding an aqueous 40% sodium hydroxide solution
  10. stirringthe mixture was stirred at room temperature for 20 hours
  11. filtrationThe deposited crystal was collected by filtration
  12. washwashed
  13. customdried

Sources & evidence

ORD record
ord-fecfe483591c4032980836263c4c9ed1
Source dataset
uspto-grants-2001_07
Patent number
US06265582B1

Reaction notes

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