1530-39-8Relevant academic research and scientific papers
Chiral Imidodiphosphoric Acid-Catalyzed Highly Diastereo- and Enantioselective Synthesis of Poly-Substituted 3,4-Dihydro-2 H-pyrans: [4 + 2] Cycloadditions of β,γ-Unsaturated α-Ketoesters and 3-Vinylindoles
Guan, Xu-Kai,Liu, Guo-Feng,An, Dong,Zhang, Heng,Zhang, Suo-Qin
supporting information, p. 5438 - 5442 (2019/08/01)
Imidodiphosphoric acids were employed to catalyze inverse-electron-demand hetero-Diels-Alder reaction of β,γ-unsaturated α-ketoesters and 3-vinylindoles. A series of optically active 3,4-dihydro-2H-pyran derivatives with three contiguous stereogenic centers was synthesized in excellent yields (70-99%), diastereoselectivities (>20:1), and enantioselectivities (73-99%). The resulting indole containing 3,4-dihydro-2H-pyran could be converted to tetrahydropyran derivatives, which appear in several biological active compounds by simple hydrogenation reduction.
Syntheses of p-terphenyls and 11,12-dihydroindeno[2,1-a]fluorene by one-pot benzannulation of Diels-Alder reactions of trans-1,2-dichloroethene and dienes
Ho, Jinn-Hsuan,Lin, Yu-Chen,Chou, Li-Ting,Chen, Ying-Zhe,Liu, Wei-Qi,Chuang, Chao-Li
supporting information, p. 1991 - 1993 (2013/04/10)
A series of substituted p-terphenyls and 11,12-dihydroindeno[2,1-a]fluorene were successfully synthesized by one-pot benzannulation of Diels-Alder reaction with 1,2-dichloroethene as an acetylene equivalent dienophile. Two chlorine atoms could be good leaving groups to easily undergo subsequent elimination reactions of Diels-Alder products at a high temperature.
Novel (E)-5-styryl-2,2′-bithiophene derivatives as ligands for β-amyloid plaques
Cui, Mengchao,Li, Zijing,Tang, Ruikun,Jia, Hongmei,Liu, Boli
experimental part, p. 2908 - 2916 (2011/07/08)
In continuation of our investigation on the bithiophene structure as potential β-amyloid probes, a series of (E)-5-styryl-2,2′-bithiophene (SBTP) derivatives was designed and synthesized. In vitro binding showed that all of them displayed high binding affinities to Aβ1-42 aggregates (Ki = 0.10-41.05 nM). Moreover, two radio-iodinated probes, [125I]-(E)-5-(4-iodostyryl)-2,2′-bithiophene ([ 125I]8) and [125I]-(E)-5-iodo-5′-(4-methoxystyryl)- 2,2′-bithiophene ([125I]31) were prepared. Both of them displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background. In vivo biodistribution in normal mice indicated that [125I]8 exhibited high initial brain uptake (2.11% ID/g at 2 min) and rapid clearance (0.41% ID/g at 30 min). These preliminary results suggest that SBTP derivatives may be served as novel β-amyloid imaging probes.
Arylethenylbenzofuroxan derivatives as drugs for chagas disease: Multigram batch synthesis ysubg a wuttug#bideb process
Porcal, Williams,Merlino, Alicia,Boiani, Mariana,Gerpe, Alejandra,Gonzalez, Mercedes,Cerecetto, Hugo
, p. 156 - 162 (2013/01/03)
In the present work, we developed robust processes for the preparation of new antitrypanosomal benzofuroxans, E and Z isomers of 5-arylethenylbenzo[1,2-c] 1,2,5-oxadiazole p1N-oxide 1-6, in muhigram batch through Wittig-Boden conditions as the key synthetic step. In these conditions, the generation of the benzofurazans, as secondary byproduct, was minimized.
Synthesis of novel sulfonyl-stabilized phosphorus ylides, and the kinetics and mechanism of their conventional and flash vacuum pyrolysis reactions
Al-Bashir, Rasha F.,Al-Awadi, Nouria A.,El-Dusouqui, Osman M.E.
, p. 1543 - 1553 (2007/10/03)
Nine substituted sulfonyl-stabilized phosphorus ylides were prepared by treating their intermediate ylide analogues with phenylmethanesulfonyl fluoride. The stoichiometric ratio of the reactants for each preparation needed to be adjusted according to the basicity of each ylide intermediate. The nine ylide compounds were then subjected to conventional (sealed-tube) gas-phase pyrolysis at 470-545 K. The pyrolytic reactions were homogeneous and obeyed a first-order rate equation. The values of the Arrhenius log A (s-1) and E a (kJ mol-1) obtained for these reactions averaged 11.12 ± 2.00 and 131.8 ± 24.4, respectively. Analysis of the pyrolysates from conventional pyrolysis and from flash vacuum pyrolysis at 600 K showed the products to be complex mixtures of triphenylphosphine, triphenylphosphine oxide, triphenylphosphine sulfide, and symmetric and unsymmetric alkenes. Conventional pyrolysis also gave novel mixed sulfones and, for the p-methoxyaryl substituent, p-anisaldehyde. The products of the reactions under study are explained on the basis of a mechanism involving a sulfonyl carbene intermediate, and the reaction mechanism is used to rationalize the kinetic results and molecular reactivities.
Synthesis and antiparasitic and antitumor activity of 2,4-diamino-6- (arylmethyl)-5,6,7,8-tetrahydroquinazoline analogues of piritrexim
Rosowsky, Andre,Papoulis, Andrew T.,Forsch, Ronald A.,Queener, Sherry F.
, p. 1007 - 1017 (2007/10/03)
Nineteen previously undescribed 2,4-diamino-6-(arylmethyl)-5,6,7,8- tetrahydroquinazolines (5a-m, 10-12) were synthesized as part of a larger effort to assess the therapeutic potential of lipophilic dihydrofolate reductase (DHFR) inhibitors against opportunistic infections of AIDS. Condensation of appropriately substituted (arylmethyl)triphenylphosphoranes with 4,4-ethylenedioxycyclohexanone, followed by hydrogenation (H2/Pd-C) and acidolysis, yielded the corresponding 4-(arylmethyl)cyclohexanones, which were then condensed with cyanoguanidine to form the tetrahydroquinazolines. Three simple 2,4-diamino-6-alkyl-5,6,7,8-tetrahydroquinazoline model compounds (9a-c) were also prepared in one step from commercially available 4-alkylcyclohexanones by this method. Enzyme inhibition assays against rat liver DHFR, Pneumocystis carinii DHFR, and the bifunctional DHFR-TS enzyme from Toxoplasma gondii were carried out, and the selectivity ratios IC50(rat)/IC50(P. carinii) and IC50(rat)/IC50(T. gondii) were compared. The three most potent inhibitors of P. carinii DHFR were the 2,5- dimethoxybenzyl (5j), 3,4-dimethoxybenzyl (5k), and 3,4,5-trimethoxybenzyl (51) analogues, with IC50 values of 0.057, 0.10, and 0.091 μM, respectively. The remaining compounds generally had IC50 values in the 0.1- 1.0 μM range. However all the compounds were more potent against the rat liver enzyme than the P. carinii enzyme and thus were nonselective. The T. gondii enzyme was always more sensitive than the P. carinii enzyme, with most of the analogues giving IC50 values of 0.01-0.1 μM. Moderate 5-10-fold selectivity for T. gondii versus rat liver DHFR was observed with five compounds, the best combination of potency and selectivity being achieved with the 2-methoxybenzyl analogue 5d, which had an IC50 of 0.014 μM and a selectivity ratio of 8.6. One compound (51) was tested for antiproliferative activity against P. carinii trophozoites in culture at a concentration of 10 μg/mL and was found to completely suppress growth over 7 days. The suppressive effect of 51 was the same as that of trimethoprim (10 μg/mL) + sulfamethoxazole (250 μg/mL), a standard clinical combination for the treatment of P. carinii pneumonia in AIDS patients. Four compounds (5a,h,k,l) were tested against T. gondii tachyzoites in culture and were found to have a potency (IC50 = 0.1-0.5 μM) similar to that of pyrimethamine (IC50 = 0.69 μM), a standard clinical agent for the treatment of cerebral toxoplasmosis in AIDS patients. Compound 5h was also active against T. gondii infection in mice when given qdx8 by peritoneal injection at doses ranging from 62.5 (initial dose) to 25 mg/kg. Survival was prolonged to the same degree as with 25 mg/kg clindamycin, another widely used drug against toxoplasmosis. Three compounds (5j-l) were tested for antiproliferative activity against human tumor cells in culture. Among the 25 cell lines in the National Cancer Institute panel for which data were confirmed in two independent experiments, the IC50 for at least two of these compounds was 50 of 50 was 0.01 μM.
Kinetic Study of the Substitution Reactions of Triphenylphosphine with Chlorobenzyl Chlorides, Dimethylbenzyl Chloride, and Methylbenzyl Bromides in Various Two-Phase Organic Solvent/Water Media
Shieh, Ruey-Lone,Lin, Ruey-Lih,Hwang, Jiann-Jyh,Jwo, Jing-Jer
, p. 517 - 523 (2007/10/03)
The kinetics of the substitution reactions of triphenylphosphine (TP) with chlorobenzyl chlorides (CBC), 2,5-dimethylbenzyl chloride (DMBC), and methylbenzyl bromides (MBB) in aprotic organic solvent was studied under the extraction by water. The effects of water, agitation, organic solvent, reactant, and temperature were investigated. These reactions take place via the SN2 mechanism and exhibit large and negative entropy of activation. The order of relative activity of solvents is CHCl3 > CH2Cl2 >> C6H6. In CHCl3, the order of relative reactivity of benzyl chloride (BC), benzyl bromide (BB), CBC, DMBC, and MBB toward reaction with TP is 2-MBB > 4-MBB > 3-MBB > BB > DMBC > BC > 2-CBC > 4-CBC > 3-CBC. These reactions produce quantitatively benzyltriphenylphosphonium salts, which are useful for synthesizing Z-form isomers of stilbenes via the two-phase Wittig reaction.
Syntheses of 2-(2-arylethyl)-1-methylimidazoles
Shafiee,Morteza-Semnani,Foroumadi
, p. 671 - 673 (2007/10/03)
2-(2-Arylethyl)-1-methylimidazoles 3 could be prepared by different methods. The best method was the Wittig reaction of aryltriphenylphosphonium chloride 8 with 2-formyl-1-methylimidazole to give compound 6. Reduction of compound 6 with Raney nickel gave compound 3.
New Results in the Synthesis of Styrylazulene Derivatives: Application of the 'Anil Synthesis' to the Preparation of Azulenes Substituted with Styryl Groups at the Seven-Membered Ring
Briquet, Anne Andree Sophie,Hansen, Hans-Juergen
, p. 1921 - 1939 (2007/10/02)
The synthesis of 4,6,8-trimethyl-1-azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde (1) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1).In the same way, guaiazulene-3-carbaldehyde (2) as well as dihydrolactaroviolin (3) yielded with 4a the corresponding styrylazulenes 6 and 7, respectively (see Table 1).It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9, respectively (cf.Scheme 1).The reaction of 4,6,8-trimethylazulene (10) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b. 4,6,8-Trimethylazulene-2-carbaldehyde (12) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH4) and dehydrogenation (MnO2) sequence (see Scheme 2).The Swern oxidation of the intermediate 2-(hydroxy-methyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf.Scheme 2).The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b, respectively (see Scheme 3).Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3).The 'anil synthesis' of guaiazulene (21) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me2N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-azulene derivatives 23 (see Table 4).In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4).The 'anil reaction' of 21 and 4-NO2C6H4CH=NC6H5 (22e) in DMF yielded no corresponding styrylazulene derivative 23e.Insteed, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene (27) was formed (see Scheme 4).The reaction of 4,6,8-trimethylazulene (10) and benzanil (22a) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf.Scheme 5).Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf.Scheme 6).However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf.Scheme 6).
Photolysis of (Arylmethyl)triphenylphosphonium Salts. Substituent, Counterion, and Solvent Effects on Reaction Products
Imrie, C.,Modro, T. A.,Rohwer, E. R.,Wagener, C. C. P.
, p. 5643 - 5649 (2007/10/02)
Quaternary (arylmethyl)phosphonium salts of the general formula ArCH2-PR3(+)Y(-) (Ar = substituted phenyl or 1-naphthyl; R = phenyl, ferrocenyl, or butyl; Y(-) = BF4(-) or halide) have been photolyzed in acetonitrile or in methanol.Photolysis involved the cleavage of the P-CH2 bond and the products derived from both, the arylmethyl radical and the carbocation, were formed.The proportion of the radical- and carbocation-derived products was determined as a function of substituents in group Ar, of groups R, counterions Y(-), and the solvent.For the nonoxidizable counterion (BF4(-), the proposed mechanism of the reaction involves initial homolysis, followed by the escape of the radical products from a solvent cage, or by the electron transfer from carbon to phosphorus, yielding the corresponding arylmethyl carbocation.The latter can either react with the solvent to form the observed carbocation-derived product or can undergo recombination with the tertiary phosphine formed to yield the starting phosphonium ion.Some indication of the "inverted substituent effect" resulting from the inhibition of single electron transfer from an easily oxidized radical was obtained.For the oxidizable counterions (halides), an additional pathway is suggested, that involves electron transfer from the anion, yielding the arylmethyl radical and the phosphine, thus decreasing the ionic/radical products ratio.
