Reaktion #69395

Reaktionsgleichung

Na2CO3

pyridine-4-carbohydrazide

HCl

dioxane

3,4-diethoxybenzonitrile

MeOH

→

4-(5-(3,4-diethoxyphenyl)-4H-1,2,4-triazol-3-yl)pyridine

Ausbeute 63.0%

Lösungsmittel

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITplaced in the refrigerator (0-5° C.) for 48 h
2. 2
   SonstigeThe mixture was bubbled with N2
3. 3
   Einengenconcentrated under reduced pressure
4. 4
   workup.ADDITIONTo the crude was added anhydrous ether
5. 5
   Sonstigethe methyl 3,4-diethoxybenzimidate salt precipitated as pale orange solid in 63% yield (1.3 g)
6. 6
   SonstigeThe product was used without further purification
7. 7
   Extraktionextracted with ether) in acetonitrile
8. 8
   Temperaturthe reaction was refluxed for 2 h
9. 9
   EinengenThe mixture was concentrated under reduced pressure
10. 10
    Temperaturthe crude was heated at 180° C. for 2 h
11. 11
    SonstigeThe product was purified by column chromatography

Vorschrift

Cold 4M HCl in dioxane (31.5 mmol, 8.87 mL) was added to a stirred solution of 3,4-diethoxybenzonitrile (7.84 mmol, 1.5 g) in anhydrous MeOH (23.53 mmol, 954 μl) and anhydrous ether (4 mL). The reaction was stirred at 0° C. for 1 h and then placed in the refrigerator (0-5° C.) for 48 h. The mixture was bubbled with N2 to eliminate HCl and concentrated under reduced pressure. To the crude was added anhydrous ether and the methyl 3,4-diethoxybenzimidate salt precipitated as pale orange solid in 63% yield (1.3 g). The product was used without further purification. To a stirred solution of the imidine (0.5 mmol, 130 mg) (freshly liberated from the imidate salt using a solution 1M of Na2CO3 and extracted with ether) in acetonitrile was added pyridine-4-carbohydrazide (0.55 mmol, 75.5 mg) and the reaction was refluxed for 2 h. The mixture was concentrated under reduced pressure and the crude was heated at 180° C. for 2 h. The product was purified by column chromatography using CH2Cl2:MeOH (9:1) to offer the product as a white solid in 65% yield (100 mg, 0.32 mmol). 1H NMR (400 MHz, CDCl3): δ8.71 (bs, 2H), 8.11 (d, J=5.2 Hz, 2H), 7.60 (s, 1H), 7.57 (d, J=8.4 Hz, 1H), 6.90 (d, J=8.4, 1H), 4.11 (q, J=6.8 Hz, 2H), 4.07 (q, J=6.8 Hz, 2H), 1.45 (t, J=7.0 Hz, 3H), 1.40 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 157.73, 150.89, 149.42, 149.14, 139.66, 121.29, 120.56, 120.06, 119.68, 113.00, 111.53, 64.82, 64.72, 14.90, 14.86. MS (EI) m/z: 311 (M+), HRMS (EI) for C17H18N4O2 (M+): calcd 311.1502. found 311.1506.

Quelle