تفاعل #1583804

معادلة التفاعل

N-methyl-2-(pyridine-3-carbothioamido)acetamide

acetonitrile

phosphorus oxychloride

→

solid

المردود 75.0%

N-methyl-2-(pyridin-3-yl)thiazol-5-amine

المردود 75.0%

المذيبات

ethyl acetate

—

hexanes

ظروف التفاعل

المعالجة

1. 1
   أخرىTo a dry 2 L round bottom flask equipped with mechanical stirrer, addition funnel
2. 2
   درجة الحرارةreflux condenser
3. 3
   أخرىoccurred from 22° C. to 34° C
4. 4
   درجة الحرارةThe reaction mixture was heated to 85° C. (
5. 5
   درجة الحرارةrefluxing gently)
6. 6
   workup.WAITAfter 3 hours
7. 7
   workup.DISSOLUTIONall of the solid had dissolved
8. 8
   أخرىforming a dark amber solution
9. 9
   درجة الحرارةto cool to 25° C.
10. 10
    أخرىthe solvent removed by rotary evaporation
11. 11
    workup.DISSOLUTIONThe residue was dissolved in water
12. 12
    workup.ADDITIONtreated with solid sodium bicarbonate until slightly basic (pH˜8) with continuous stirring
13. 13
    أخرىto form after a few minutes
14. 14
    workup.STIRRINGto stir at 25° C. for 16 hours
15. 15
    ترشيحThe brown solid was collected by vacuum filtration
16. 16
    غسيلwashed with water
17. 17
    أخرىThis gave a tan solid wet cake (91 g) which
18. 18
    أخرىwas then dried in vacuo at 40° C. to a constant weight

الإجراء التجريبي

To a dry 2 L round bottom flask equipped with mechanical stirrer, addition funnel and reflux condenser was charged N-methyl-2-(pyridine-3-carbothioamido)acetamide (100 g, 478 mmol) and acetonitrile (1 L). To this mixture was added phosphorus oxychloride (256 g, 1672 mmol) portionwise over 10 minutes. The reaction mixture was stirred at ambient temperature for 10 minutes during which time a slight exotherm occurred from 22° C. to 34° C. The reaction mixture was heated to 85° C. (refluxing gently). After 3 hours, all of the solid had dissolved, forming a dark amber solution. Analysis of an aliquot by TLC (70% ethyl acetate : 30% hexanes) after 4 hours indicated that the reaction was essentially complete. The reaction mixture was allowed to cool to 25° C. and the solvent removed by rotary evaporation. The residue was dissolved in water and treated with solid sodium bicarbonate until slightly basic (pH˜8) with continuous stirring. A brown precipitate started to form after a few minutes. The mixture was continued to stir at 25° C. for 16 hours. The brown solid was collected by vacuum filtration and washed with water. This gave a tan solid wet cake (91 g) which was then dried in vacuo at 40° C. to a constant weight. This gave N-methyl-2-(pyridin-3-yl)thiazol-5-amine as a sand colored solid (68.5 g, 75% yield); mp 140-141° C.; 1H NMR (400 MHz, CDCl3) δ 8.98 (dd, J=2.3, 0.7 Hz, 1H), 8.53 (dd, J=4.8, 1.6 Hz, 1H), 8.07 (ddd, J=8.0, 2.2, 1.7 Hz, 1H), 7.40-7.21 (m, 1H), 6.96 (s, 1H), 4.18 (s, 1H), 2.96 (s, 3H); 13C NMR (101 MHz, CDCl3) δ153.23, 149.15, 146.54, 132.23, 130.47, 123.65, 121.20, 34.48; Anal. Calc'd. for C9H9N3S: C, 56.52; H, 4.74; N, 21.97; S, 16.77. Found: C, 56.31: H, 4.74; N, 21.81; S, 16.96.

المصدر