Direct metalation of heteroaromatic esters and nitriles using a mixed lithium-cadmium base. Subsequent conversion to dipyridopyrimidinones.

International audienceAll pyridine nitriles and esters were metalated at the position next to the directing group using (TMP)(3)CdLi in tetrahydrofuran at room temperature. The 2-, 3-, and 4-cyanopyridines were treated with 0.5 equiv of base for 2 h to afford, after subsequent trapping with iodine, the corresponding 3-iodo, 2-iodo, and 3-iodo derivatives, respectively, in yields ranging from 30 to 61%. Cyanopyrazine was similarly functionalized at the 3 position in 43% yield. Ethyl 3-iodopicolinate and -isonicotinate were synthesized from the corresponding pyridine esters in 58 and 65% yield. Less stable ethyl 4-iodonicotinate also formed under the same conditions and was directly converted to ethyl 4-(pyrazol-1-yl)nicotinate in a two-step 38% yield. All three ethyl iodopyridinecarboxylates were involved in a one-pot palladium-catalyzed cross-coupling reaction/cyclization using 2-aminopyridine to afford new dipyrido[1,2-a:3',2'-d]pyrimidin-11-one, dipyrido[1,2-a:4',3'-d]pyrimidin-11-one, and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one in yields ranging from 50 to 62%. A similar cross-coupling/cyclization sequence was applied to methyl 2-chloronicotinate using 2-aminopyridine, 2-amino-5-methylpyridine, and 1-aminoisoquinoline to give the corresponding tricyclic or tetracyclic compounds in 43-79% yield. Dipyrido[1,2-a:4',3'-d]pyrimidin-11-one and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one showed a good bactericidal activity against Pseudomonas aeroginosa . Dipyrido[1,2-a:2',3'-d]pyrimidin-5-one and pyrido[2',3':4,5]pyrimidino[2,1-a]isoquinolin-8-one showed a fungicidal activity against Fusarium and dipyrido[1,2-a:4',3'-d]pyrimidin-11-one against Candida albicans . Ethyl 4-(pyrazol-1-yl)nicotinate and dipyrido[1,2-a:2',3'-d]pyrimidin-5-one have promising cytotoxic activities, the former toward a liver carcinoma cell line (HEPG2) and the latter toward a human breast carcinoma cell line (MCF7

Direct metallation of thienopyrimidines using a mixed lithium-cadmium base and antitumor activity of functionalized derivatives

International audienceA series of thieno[2,3-d]- and thieno[3,2-d]pyrimidines have been easily synthesized using as key step a deproto-cadmiation-trapping sequence. Some of the compounds thus synthesized were screened for anti-cancer (cytotoxic) activities, and (S)-2-(6-iodo-2-phenylthieno[2,3-d]pyrimidin- 4-ylamino)-3-phenylpropanoic acid proved to have a significant activity towards liver, human breast and cervix carcinoma cell lines

Réactivité des molécules organiques à très basses températures (22 - 300 k) pour la modélisation des milieux extra-terrestres froids

Cette thèse présente l'étude expérimentale de la cinétique des réactions entre espèces neutres d'importance astrophysique, sur une large gamme de température (22 300 K). Ces très températures basses ont été obtenues par la technique CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme). Les études de cinétique des réactions du radical cyano (CN) avec le cyanoacétylène (HC N), le diacétylène (C H ) et le méthanol (CH OH) ont été effectuées pour la première fois en-dessous de la température ambiante (~300 K) en utilisant la technique PLP-LIF (Pulsed Laser Photolysis - Laser Induced Fluorescence). Les coefficients de vitesse des réactions du radical éthynyle (C H) avec HC N, C H ont été mesurées en utilisant la technique PLP-CL (Pulsed Laser Photolysis - Chemiluminescence). Ces réactions sont rapides même à très basses températures. Ces études représentent un pas important vers la compréhension des processus chimiques impliqués dans la synthèse des molécules complexes, comme les polyynes [H(C )nH] et les cyanopolyynes [H(C )nCN] dans le milieu interstellaire et dans les atmosphères planétaires, en particulier celle de Titan.This thesis presents studies of the kinetics of reactions between neutral species of astrophysical importance, over a wide range of temperature, from 300 K down to 22 K. These extremely low temperatures were provided by the CRESU technique (a French acronym standing for Cinétique de Réaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in Uniform Supersonic Flow). The kinetics of the reactions of the cyano radical (CN) with cyanoacetylene (HC3N), diacetylene (C H ) and methanol (CH OH) have been investigated for the first time below room temperature, using the PLP-LIF technique (Pulsed Laser Photolysis - Laser Induced Fluorescence). Rate coefficients of the reactions of the ethynyl radical (C H) with HC N, C H and 1,3-butadiene (C H ) have been measured, employing the PLP-CL technique (Pulsed Laser Photolysis - Chemiluminescence). These reactions are fast even at very low temperatures. These studies represent an important step towards the understanding of chemical processes involved in the synthesis of complex molecules, such as polyynes [H(C )nH] and cyanopolyynes [H(C )nCN] in the interstellar medium and in planetary atmospheres, especially that of Titan.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

State-to-state study of the D + H 2 ( v = 0, j ) collisions and its astrophysical implications

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Low Temperature Rate Coefficients for the Reaction CN + HC3N.

International audienceThe reaction of CN radicals with HC3N is of interest for interstellar and circumstellar chemistry as well as for the chemistry of Titan's atmosphere, as part of a general scheme for cyanopolyyne synthesis within these low temperature environments. Here, we present the first experimental measurements of its rate coefficient below room temperature down to 22 K, employing the CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in Uniform Supersonic Flow) technique coupled with pulsed laser photolysis-laser-induced fluorescence. A novel pulsed version of the CRESU technique employing a new spinning disk valve was used for some of the kinetics measurements. The measurements were in excellent agreement with the only previous determination at room temperature and show a marked increase in the rate coefficient as the temperature is lowered, with the results being well represented by the equation k(T) = 1.79 × 10(-11)(T/300 K)(-0.67) cm(3) molecule(-1) s(-1), with a root-mean-square (statistical) error of 0.61 × 10(-11) cm(3) molecule(-1) s(-1), to which should be added 10% estimated likely systematic error. High accuracy ab initio quantum chemical calculations coupled with variational two-transition state theory calculations were also performed and demonstrate excellent agreement within the combined experimental and predicted theoretical uncertainties. The theoretical rate coefficients, adjusted within expected uncertainties, can be accurately reproduced over the 5 to 400 K temperature range by the expression [(1.97 × 10(-8)) T (-1.51) exp(-3.24/T) + (4.85 × 10(-13)) T (0.563) exp (17.6/T)] cm(3) molecule(-1) s(-1), where T is in K. The new measurements are likely to be of interest to astrochemical and planetary atmospheric modelers

Low temperature reaction kinetics and organic synthesis in space: Organonitrogen chemistry

International audienc

Formation of HC5N in space environments

International audienc

Low Temperature Kinetics of the Reaction Between Methanol and the CN Radical

International audienceMethanol (CH3OH) is considered by astronomers to be the simplest complex organic molecule (COM) and has been detected in various astrophysical environments, including protoplanetary disks, comets, and the interstellar medium (ISM). Studying the reactivity of methanol at low temperatures will aid our understanding of the formation of other complex and potentially prebiotic molecules. A major destruction route for many neutral COMs, including methanol, is via their reactions with radicals such as CN, which is ubiquitous in space. Here, we study the kinetics of the reaction between methanol and the CN radical using the well-established CRESU technique (a French acronym standing for Reaction Kinetics in Uniform Supersonic Flow) combined with Pulsed-Laser Photolysis–Laser-Induced Fluorescence (PLP-LIF). Electronic structure calculations were also performed to identify the exothermic channels through which this reaction can proceed. Our results for the rate coefficient are represented by the modified Arrhenius equation, k(T) = 1.26 × 10^–11(T/300 K)^−0.7 exp(−5.4 K/T), and display a negative temperature dependence over the temperature range 16.7—296 K, which is typical of what has been seen previously for other radical-neutral reactions that do not possess potential energy barriers. The rate coefficients obtained at room temperature strongly disagree with a previous kinetics study, which is currently available in the Kinetics Database for Astrochemistry (KIDA) and therefore used in some astrochemical models

Kinetics of the reaction between the CN radical and methanol at low temperatures using the CRESU technique

International audienceThe interstellar medium is host to a rich chemistry that produces a number of complex organic molecules (COMs) i.e. organic molecules with six or more atoms. A large number of COMs have been observed in astrophysical regions, even in very cold (<10 K) environments, challenging the widely accepted "warm-up" model in which COMs are formed on the surface of icy dust grains and delivered to the gas phase during star-formation. Methanol (CH3OH) is a COM of particular interest because it is an important parent species of larger and more complex molecules in the gas and ice phases. Neutral-radical reactions are an important destruction route for many species and, given the widespread abundance of the CN radical in space, the reaction between methanol and the CN radical is of significant interest. Here, we study the kinetics of the reaction between CH3OH and the CN radical using the well-established CRESU (Reaction Kinetics in Uniform Supersonic Flow) technique, combined with Pulsed Laser Photolysis-Laser-Induced Fluorescence (PLP-LIF). Our results display a negative temperature dependence, typical of what has been seen previously for other radical-neutral reactions that do not possess potential barriers. The rate coefficient obtained at room temperature strongly disagrees with that measured by Sayah et. al. in a flow cell. The reaction products and their branching ratios are of significant interest, particularly the branching ratio between the radicals methoxy (CH3O) and hydroxy-methanol (CH2OH). While the PLP-LIF technique is a powerful technique for the measurement of overall, temperature-dependent reaction rate coefficients, it is not well suited to measurements of product branching ratios. We are conducting electronic structure calculations for this reaction in order to provide a theoretical perspective. We are also developing a new setup integrating chirped-pulse broad-wave microwave spectroscopy with continuous flow-CRESU (CRESUCHIRP), which will allow us to identify reaction products and their branching ratios