SYNTHESIS OF PYRAZOLE-4-CARBALDEHYDE
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solutions were washed with brine, dried over MgSO4, and evaporated to dryness.
The crystalline solid was washed with a small amount of CCl4 and dried in the
air, affording 736.5 g (86%) of 6 as a light creamy powder.
1
Mp 107.0–107.5 ꢀC (lit.[2] 107–108 ꢀC). H NMR (CDCl3, 25 ꢀC): d 9.49 (br.s,
13
1H, NH), 7.6 (s, 2H, CH); C NMR (DMSO-d6, 25 ꢀC): d 133.8, 56.5; MS (EI)
m=z: 194 (Mþ, 100%), 127 (Iþ, 18%), 67 (Mþ ꢃ I, 20.7%).
1-(1-Ethoxyethyl)-4-iodo-1H-pyrazole (8)
Into a 4-iodo-1H-pyrazole (6) solution (80 g, 406 mmol) in 300 mL of benzene,
50 mL of 30% HCl (in Et2O) and 50 mL (37.5 g, 502 mmol, 1.27 eq) of ethyl vinyl
ether were added. The resulting mixture was stirred under nitrogene at 50 ꢀC for
3 h. Then it was cooled and left at room temperature overnight. The organic phase
was extracted with 50 mL of saturated KHCO3 solution, washed with brine, and
dried over MgSO4. The solvent was evaporated under reduced pressure (bath tem-
perature 40 ꢀC), and the resulting light yellow oil was used in the next step without
purification. Yield 106 g (98%). Analytical sample was purified by preparative TLC
(Rf ¼ 0.73, CH2Cl2–hexane 2:1 v=v).
1H NMR (CDCl3, 25 ꢀC): d 7.6 (s, 1H, CH), 7.5 (s, 1H, CH); 5.45 (q, 1H,
J ¼ 6.1 Hz, CH), 3.3 (m, 2H, CH2), 1.6 (d, 3H, J ¼ 6.1 Hz, CH3), 1.1 (t, 3H,
13
J ¼ 6.9 Hz, CH3); C NMR (CDCl3, 25 ꢀC): d 144, 130.6, 88, 64.5, 57.5, 22, 14.6;
MS (EI) m=z: 266 (Mþ, 13%), 222 (17%), 194 (33%), 144 (17%), 73 (83%), 45 (100%).
1H-Pyrazole-4-carbaldehyde Hydrochloride (1)
Grignard reagent (1.4 M approx.) was prepared in usual manner from 9.5 g Mg
(390 mmol) and 29 mL (42.5 g, 390 mmol) EtBr in 250 mL of dry THF. To a
mechanically stirred solution of 8 (80 g, 300 mmol) in 250 mL of dry THF solution
of EtMgBr was added dropwise at þ5–7 ꢀC under an argon atmosphere. A jacketed
dropping funnel was used, and warm water was passed through the jacket to prevent
crystallization of the Grignard solution. Then the funnel was rinsed with 70 mL of
tetrahydrofuran (THF), and the reaction mixture was additionally stirred for 1 h.
A tarry matter which can present in the mixture dissolved within this period of time.
The clear dark solution was cooled again to 0 ꢀC, and the solution of 34.8 mL DMF
(32.9 g, 450 mmol) in 30 mL of THF was added slowly. The resulting solution was
left at room temperature overnight (a white crystalline precipitate was formed); then
it was cooled to 0 ꢀC and decomposed by the careful addition of 100 mL of saturated
NH4Cl solution. After that, water (80 mL) was added to dissolve completely the
inorganic salts. The organic phase was separated, and the water phase was extracted
by Et2O (3 ꢂ 200 mL). Combined phases were washed with brine, dried subsequently
over NaSO4 (to remove most of the water) and MgSO4, and evaporated in vacuo.
The oily residue (42 g) was redissolved in 250 mL of Et2O, and 5 g of anhydrous
MgSO4 were added to the turbid solution. Then it was filtered through the Celite
pad (5 mm). The clear solution was transferred to a beaker, and HCl (saturated
solution in anhydrous Et2O, approx. 27–30% by weight) was slowly added with con-
tinious stirring. After the first portions of the solution (usually 10–15 mL) were
added, a dark yellow tar was formed. The further addition of HCl solution led to
Taydakov, Ilya V.
