Reaction #1483049

Reaction equation

sodium nitrite

4-(hydroxymethyl)-benzenecarboximidic acid, ethyl ester, hydrochloride

formamidine acetate

hydrazine

→

(4-(1,2,4,5-tetrazin-3-yl)phenyl)methanol

Yield 21.3%

Solvents

acetic acid

water

Conditions

Workup

1. 1
   workup.STIRRINGto stir for 15 minutes
2. 2
   OtherThe aqueous crude reaction
3. 3
   Extractionwas subsequently extracted with methylene chloride (4×10 mL)
4. 4
   DryingThe organic extracts were dried with MgSO4
5. 5
   OtherAfter solvent removal
6. 6
   Otherthe crude pink product was purified by flash chromatography (silica gel)
7. 7
   Washfirst washing with 100% methylene chloride

Procedure

To a mixture of 4-(hydroxymethyl)-benzenecarboximidic acid, ethyl ester, hydrochloride (1 mmol, 216 mg) and formamidine acetate (5 mmol, 521 mg) was added anhydrous hydrazine (20 mmol, 630 uL) the resulting viscous oil was allowed to stir. After 1 hour, acetic acid (3 mL) was added followed by sodium nitrite (690 mg, 10 mmol) as a finely divided powder. The now bright pink solution was allowed to stir for 15 minutes and then diluted with 15 mL of water. The aqueous crude reaction was subsequently extracted with methylene chloride (4×10 mL). The organic extracts were dried with MgSO4. After solvent removal, the crude pink product was purified by flash chromatography (silica gel) first washing with 100% methylene chloride, followed by methylene chloride with 1% methanol, giving (4-(1,2,4,5-tetrazin-3-yl)phenyl)methanol (40 mg, 21%) as a bright pink solid. LRMS-ESI [M+H]− calcd. for C9H9N4O−: 189.08, found: 188.8.

Source