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With methyl nitrite; sodium In propan-1-ol at 20℃; for 0.333333h; Overall yield = 76 %; |
Synthesis of cyanoximes HPiPCO (2) and HMCO (5)
The general procedure includes the room temperature nitrosation reaction of precursors 1 and 4 with gaseous methylnitrite, CH3ONO, at basic conditions according to published procedures [25c,46] (Scheme 1; ESI 1). (0012) Details of the syntheses are the following: for the HPiPCO, 2 - 60mL of 1-propanol in a round-bottom flask in which 0.40g (17.4mM) of thinly sliced metallic sodium was dissolved. Both solutions were combined only before gaseous CH3ONO was allowed to pass through the mixture in order to avoid Thorpe condensation reactions encountered in the past. These occur between deprotonated substituted acetonitriles at basic conditions [47]. In a separate Erlenmeyer flask 2.646g (17.4mM) of 1 were dissolved in ∼100mL of 1-propanol under stirring. (0013) For the HMCO, 5 - 70mL of 1-propanol in which 0.45g (19.6mM) of thinly sliced metallic sodium were dissolved; 3.016g (19.6mM) of 4 were dissolved in 80mL of n-propanol under intense stirring, and both solutions were combined immediately before CH3ONO introduction. The methylnitrite generator (which consisted of a three-necked 2 L flask with a 1:1 (by volume) mixture of methanol in water that contained 22g of NaNO2, and an addition funnel with cold, ∼0°C, dilute 1:5 H2SO4 (ESI 1) was connected via glass pipe and a small piece of Tygon tube, to the two flasks with basic solutions of 1 and 4 as outlined above. A flow of gaseous CH3ONO started with the slow addition of sulfuric acid to the methanol-water-sodium nitrite mixture. The gas allowed passing through mixtures of 1 and 4 within ∼20min. The color of these mixtures immediately changed to a bright-yellow, and soon thick yellow precipitates of Na-salts of HPiPCO and HMCO formed. Both flasks were left in the refrigerator for ∼10h at +4°C, and then the solvent was removed under vacuum using the rotary evaporator, followed with drying on an oil pump at ∼40°C for 1h. Dried yellow solid residues from both flasks was re-dissolved in 100mL of distilled water in separate 250mL beakers forming yellow solutions, which were then acidified to a pH∼4 with dilute HCl (1:5) added dropwise under stirring. The HPiPCO (2) as off-white thick precipitate immediately formed in a beaker with nitrosated precursor 1, was filtered, washed with water and then dried under vacuum in a dessicator. The cyanoxime HMCO, 5, has better solubility in water and did not precipitate, and was extracted from the aqueous solution which, prior to this was saturated with solid NaCl, with three portions of diethyl ether (20, 30 and 50mL), which were combined and dried over MgSO4. Ether was removed under vacuum resulting in an off-white solid of pure HMCO. The HPiPCO (2) was obtained at 76% yield, it melts at 159°C; Rf=0.55 in ethanol/CHCl3=9:1 mobile phase. The 1H NMR, ppm, dmso-d6: 14.31 (OH), ring protons - 3.54 (CH2 ortho- to N), 2.50 (CH2 meta- to N), 1.57 (CH2, para- to N). Anal. Calc. for 2, C8H11N3O2:C, 53.03; H, 6.12; N, 23.19;. Found: C, 53.10; H, 6.07; N, 22.96%. Bands in the IR spectrum of 2, cm-1 (KBr): 3420, 2940, 2890, 2240, 1630, 1042. The HMCO ( 5) was obtained at ∼60% yield, it has m.p. 155°C; Rf=0.44 in EtOAc/hexane=2:1 mobile phase. The 1H NMR, ppm, dmso-d6: 14.29 (OH), ring protons - 3.30 (CH2 next to O), 2.50 (CH2 next to N). Anal. Calc. for 5, C7H9N3O3: C, 45.90; H, 4.95; N, 22.94. Found: C, 45.78; H, 5.09; N, 22.84%. Bands in the IR spectrum of 5, cm-1 (KBr): 3430, 2977, 2834, 2235, 1627, 1010. Both cyanoximes are well soluble in ether, alcohols, acetone, acetonitrile, DMF, SMSO, pyridine (with color change to yellow due to deprotonation), but are insoluble in hydrocarbons and CCl4. |
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