2-Pyrazinecarboxylic acid, ethyl ester

Brown Low Melting Solid

General procedure: Indol-3-acetic acid or 2-pyrazine carboxylic acid (5.5 mmol) were heated under reflux for 3 h in 90 mL ethanol and 15 mL concentrated H2SO4. The solution was neutralized with saturated Na2CO3 solution and filtered. The volume was reduced in vacuum and extracted with four 30 mL aliquots of dichloromethane. The combined fractions were washed with 10 mL of water and dried over anhydrous MgSO4. The dichloromethane was removed using vacuum to yield the ethyl carboxylate derivatives, 8a mp. 1–2 °C(Lit. 1–2 °C, Vlaovic et al., 1990) or 8b mp. 46–47 °C (Lit. 48–49 °C, Yoshino et al., 2006) which crystallized on cooling.To a solution of pyrazinecarbonitrile (1.00 g, 9.5 mmol) in dry ethanol (30 ml) was introduced a stream of dry HCl gas bubbled through the solution with stirring. Shortly after the HCl was introduced the temperature quickly rose requiring cooling with an ice/water bath. At this time a heavy white precipitate had fonned and after 2 h the gas inlet was replaced with a calcium' chloride drying tube and the reaction mixture stirred overnight. The HC1 gas stream was re-introduced into the reaction mixture for 2 h before again replacing the gas inlet with a drying tube and stirring for 1 h. Dry diethyl ether (45 ml) was then added to the mixture and stirring continued for 10 min before the solid was filtered under nitrogen using a Schlenk apparatus. The collected material was washed with dry diethyl ether (3 x 20 ml) and dried under vacuum to give 1.59 g of a highly moisture- sensitive white powder. nmr revealed the solid to be a mixture of the desired ethyl pyrazine-2-carbimidate hydrochloride (65percent) and the two hydrolysis products pyrazine-2- carboxamide (30percent) and ethyl pyrazine-2-carboxylate (5percent).*H nmr (400 MHz, de-dmso) δ 1.49, t (J = 7.0 Hz), 3H, OEt; 4.73, q (J = 6.9 Hz), 2H, OEt; 7.85, br, lH, C=NHGeneral procedure: A mixture of the ester derivative 8a or 8b (5.5 mmol) and hydrazine hydrate (11 mmol) in 50 mL of ethanol was heated under reflux for 6 h. The reaction mixture was left overnight at room temperature, and the solid which separated was collected by filtration. The solid was then washed with ethanol, dried, and recrystallized from ethanol (Yoshino et al., 2006; Vlaovic et al., 1990).To as stirred solution of Ethyl pyrazine-2-carboxylate (450 mg, leq, 0.986 mmoles) in ethanol (20 ml) was added hydrazine Hydrate (65.13 mg, l.2eq, and 1.184 m moles). Reaction mixture was refluxed for 3 hour. Reaction was monitored by NMR. Reaction Mixture was concentrated under reduced pressure to obtained ppt. was triturated with hexane to obtained pyrazine-2-carbohydrazide (340 mg, Brown Solid). XH NMR (400 MHz, DMSO-ri6) d 10.13 (br. s., 1H), 9.13 (d, J = 1.32 Hz, 1H), 8.83 (d, J= 2.19 Hz, 1H), 8.59 - 8.78 (m, 1H), 4.65 (br. s., 2H).

Molecular Weight:152.15
XLogP3:0.3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:152.058577502
Monoisotopic Mass:152.058577502
Topological Polar Surface Area:52.1
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes