503-20-8Relevant articles and documents
Synthesis of 5-Fluorocytosine Using 2-Cyano-2-fluoroethenolate as a Key Intermediate
Dietz, Jule-Philipp,Derstine, Brenden P.,Ferenc, Dorota,Crawford, Evan T.,Arduengo, Anthony J.,Gupton, B. Frank,McQuade, D. Tyler,Opatz, Till
, p. 5519 - 5526 (2019/07/17)
There is an urgent demand for 5-fluorocytosine (5-FC) due to its activity against HIV-induced fungal infections as well as its use as a key intermediate in the synthesis of the clinically highly important anti-HIV drug emtricitabine (FTC). We report a simple, low-cost five steps synthesis of 5-FC starting from chloroacetamide. Overall yields up to 46 % were achieved and the route is devoid of any chromatographic purifications. The previously unknown key intermediate (Z)-2-cyano-2-fluoroethenolate is obtained through a Claisen-type condensation from fluoroacetonitrile. As the direct cyclization with urea only gave poor yields, 5-fluoro-2-methoxypyrimidin-4-amine, 5-fluoro-2-(methylsulfanyl)pyrimidin-4-amine and 5-fluoropyrimidine-2,4-diamine served as synthetic intermediates.
A method for synthesizing fluorine second grade nitrile
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Paragraph 0035-0038, (2017/03/17)
The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing fluoroacetonitrile. The method comprises the following steps: performing substitution reaction on an acetonitrile derivative and inorganic fluoride salt in a polar solvent, and distilling and purifying for multiple times, thereby obtaining a high-purity product fluoroacetonitrile, wherein the formula of the substation reaction is YF+XCH2CN->FCH2CN+YX. According to the method, the acetonitrile derivative and the inorganic fluoride salt are adopted to react to obtain a target product at one time, virulent raw materials are avoided, the process route is shortened, and the yield is high; as the polar organic solvent which is low in price, easy to obtain and environment-friendly is adopted, environment pollution is avoided; the method is conductive to achieving industrialization production of fluoroacetonitrile, is gentle in reaction condition, low in production cost, high in yield and environment-friendly.
Kinetics of the reactions of acetonitrile with chlorine and fluorine atoms
Tyndall, Geoffrey S.,Orlando, John J.,Wallington, Timothy J.,Sehested, Jens,Nielsen, Ole J.
, p. 660 - 668 (2007/10/03)
The rate coefficients for the reactions of chlorine and fluorine atoms with acetonitrile have been measured using relative and direct methods. In the case of chlorine atoms the rate coefficient k1 was measured between 274 and 345 K using competitive chlorination and at 296 K using laser flash photolysis with atomic resonance fluorescence. The rate coefficient measured at ambient temperature (296 ± 2 K) is (1.15 ± 0.20) × 10-14 cm3 molecule-1 s-1, independent of pressure between 5 and 700 Torr (uncertainties are 2 standard deviations throughout). This result is a factor of 6 higher than the currently accepted value. The results from the three independent determinations reported here yield the Arrhenius expression k1 = (1.6 ± 0.2) × 10-11 exp[-(2140 ± 200)/T] cm3 molecule-1 s-1. Product studies show that the reaction of Cl atoms with CH3CN proceeds predominantly, if not exclusively, by hydrogen abstraction at 296 K. The rate coefficient for the reaction of fluorine atoms with acetonitrile was measured using both the relative rate technique and pulse radiolysis with time-resolved ultraviolet absorption spectroscopy. The rate coefficient for the reaction of F atoms with CH3-CN was found to be dependent on total pressure. The observed rate data could be fitted using the Troe expression with Fc = 0.6, k0 = (2.9 ± 2.1) × 10-28 cm6 molecule-2 s-1, and k∞ = (5.8 ± 0.8) × 10-11 cm3 molecule-1 s-1, with a zero pressure intercept of (0.9 ± 0.4) × 10-11 cm3 molecule-1 s-1. The kinetic data suggest that the reaction of F atoms with CH3CN proceeds via two channels: a pressure-independent H atom abstraction mechanism and a pressure-dependent addition mechanism. Consistent with this hypothesis, two products were observed using pulsed radiolysis with detection by UV absorption spectroscopy. As part of the product studies, relative rate techniques were used to measure k(Cl+CH2ClCN) = (2.8 ± 0.4) × 10-14 and k(F+CH2FCN) = (3.6 ± 0.2) × 10-11 cm3 molecule-1 s-1.
Gas-phase SN2 and E2 reactions of alkyl halides
DePuy, Charles H.,Gronert, Scott,Mullin, Amy,Bierbaum, Veronica M.
, p. 8650 - 8655 (2007/10/02)
Rate coefficients have been measured for the gas-phase reactions of methyl, ethyl, n-propyl, isopropyl, tert-butyl, and neopentyl chlorides and bromides with the following set of nucleophiles, listed in order of decreasing basicity: HO-, CH3O-, F-, HO- (H2O), CF3CH2O-, H2NS-, C2F5CH2O-, HS-, and Cl-. For methyl chloride the reaction efficiency first falls significantly below unity with HO- (H2O) as the nucleophile and for methyl bromide with HS- as the nucleophile; in both cases the overall reaction exothermicity is about 30 kcal mol-1. Earlier conclusions that these halides react slowly with stronger bases are shown to be in error. In the region where the rates are slow oxygen anions react with the alkyl chlorides and bromides by elimination while sulfur anions of the same basicity react by substitution. This difference is due to a slowing down of elimination with the sulfur bases; sulfur anions show no increased nucleophilicity as compared to oxy anions of the same basicity. Rate coefficients have also been measured for reaction of methyl fluoride with HO- and CH3O- and ethylene oxide with HO-, CH3O-, and F-. All of these rates are slow but measurable; combining the results of these experiments with those of the alkyl chlorides and bromides suggests that the gas-phase barrier to the symmetrical SN2 reaction of F- with methyl fluoride is lower than previous estimates. We have also measured rates for reaction of allyl chloride with F-, H2NS-, and HS-, chloromethyl ether with H2NS- and HS-, chloroacetonitrile with F-, H2NS-, HS-, and 37Cl-, bromoacetonitrile with Cl- and 81Br-, and α-chloroacetone with H2NS-, HS-, and 37Cl-. Our results also imply that the gas-phase SN2 barrier for Br- reacting with methyl bromide is nearly equal to the ion-dipole attraction energy of the reactants, in agreement with previous estimates.
