Conversion of 3,4-Dihydroxypyrrolidine-2,5-Dione to Maleimide through Tosylation and Mechanism Study by DFT

Pyrrolidine-2,5-dione and maleimide are important scaffolds of many organic substances, and their derivatives are now attracting more and more interests from researchers in organic synthesis, medicinal chemistry, and drug development. Tosyloxy (-OTs) group is an important functional group widely used in organic synthesis, because it can be readily prepared from alcohols and is an excellent leaving group. However, surprisingly, substances bearing tosyloxy groups on pyrrolidine-2,5-dione or maleimide scaffolds are very rare. In this study, we discovered that, when treated with TsCl/Et3N,?trans-3,4-dihydroxypyrrolidine-2,5- dione will eliminate a TsOH molecule to form monotosyloxymaleimide. Thermodynamic and kinetic factors affecting this reaction were investigated by theoretical computation using density functional theory (DFT), and the possible reaction mechanism was proposed based on the computation results. Our results showed that tosylates of trans -3,4-dihydroxypyrrolidine- 2,5-dione, either monotosylate or ditosylate, are thermodynamically instable and may spontaneously convert to maleimides. This knowledge could be useful in understanding the properties of pyrrolidine-2,5-diones and maleimides, as well as the related organic synthesis.

Syntheses and Crystal Structures of Two Novel Spiro Compounds Containing 1,5-Dioxaspiro[5.5]undecane-2,4-dione

Two novel spiro compounds,3-benzylidene-1,5-dioxaspiro[5.5]undecane-2,4-dione 1 and 3-（2-fluorobenzylidene）-1,5-dioxaspiro[5.5]undecane-2,4-dione 2,have been synthesized and characterized by X-ray single-crystal diffraction,IR and elemental analysis.Compound 1 belongs to the monoclinic system,space group P21/n with a=12.326（3）,b=5.6420（11）,c=20.089（4）,β= 101.79（3）o,C16H16O4,Mr= 272.29,V=1367.7（5）3,Z=4,Dc=1.322g/cm3,F（000）=576,μ（MoKa）=0.095 mm-1,the final R=0.0420 and wR=0.1159.Compound 2 is of monoclinic system,space group P21/n with a=12.283（3）,b=5.6367（11）,c=20.055（4）,β=102.00（3）o,C16H15FO4,Mr=290.28,V=1358.2（5）3,Z=4,Dc=1.420 g/cm3,F（000）=608,μ（MoKa）=0.110 mm-1,the final R=0.0353 and wR=0.0860.

Synthesis and bioactivity of novel 3-(1-hydroxyethylidene)-5-substituted-pyrrolidine-2,4-dione derivatives

Ten novel 5-substituted derivatives of 3-（1-hydroxyethylidene）pyrrolidine-2,4-dione were synthesized. The compounds were confirmed by IR, 1H NMR, MS and elemental analysis. The bioassay indicated that these compounds showed noticeable herbicidal activities, and compounds 6f and 6j exhibited excellent inhibitory activities against the stalk of Echinochloa crusgalli, with ECso values of 94.4 and 72.7 rag/L, respectively.

Syntheses and Crystal Structures of 3,3'-(9,10-Anthrylene)bis-pentane-2,4-dione and 3-(2-Methoxy-1-naphthalenyl)-pentane-2,4-dione

Two compounds 3,3'-(9,10-anthrylene)bis-pentane-2,4-dione 1 and 3-(2-methoxy-1-naphthalenyl)-pentane-2,4-dione 2 were synthesized by the direct arylation of pentane-2,4-diones in the presence of Mn(OAc)3 and H3PO4. Their crystal structures were determined by X-ray diffraction method. Compound 1, C24H22O4, Mr = 374.4, crystallized in the monoclinic system, space group P21/a with a = 7.393(4), b = 14.308(5), c = 10.099(5) ? = 110.8(4)? V = 999.0 (9) 3, Z = 2, Dc = 2.49g/cm3, F(000) = 392, ?= 0.78cm-1, final R = 0.050 and Rw = 0.057 for 1144 observed reflections with I≥3.00 ?(I). The molecular backbone is the anthracene ring, and two acetoacetone groups are perpendicular to the anthracene ring at 9,10 positions. Compound 2, C16H16O3, Mr = 256.3, crystallized in monoclinic system, space group C2 with a = 14.369(3), b = 7.480 (1), c = 15.878 (2) ? = 128.46(1)? V = 1336.3(4) ?, Z = 4, Dc = 1.27g/cm3, F(000) = 544, ?= 0.81cm-1. The structure was solved by direct methods and refined by full-matrix least-squares method, final R = 0.044 and Rw = 0.040 for 764 observed reflections with I ≥3.00(I). The acetoacetone group in compound 2 is also vertical to the naphthalene ring.

Palladium-catalyzed stereoselective decarboxylative[4+2]cyclization of 2-methylidenetrimethylene carbonates with pyrrolidone-derived enones:Straightforward access to chiral tetrahydropyran-fused spiro-pyrrolidine-2,3-diones

A novel asymmetric[4+2]cycloaddition of 2-methylidenetrimethylene carbonate with pyrrolidonederived enones has been achieved to produce the functionalized tetrahydropyran-fused spirocyclic scaffolds via palladium-catalysis.An array of enantioenriched spiro-pyrrolidine-2,3-diones bearing adjacent quaternary and tertiary stereocenters are obtained in high yields with excellent enantioselectivities(up to 96% yield and 99% ee).The further transformation of the product has been accomplished for the construction of medical interesting β^(2,2)-amino acids and β-lactams.Preliminary mechanistic research was well conducted.

Synthesis and bioactivity of novel strobilurin derivatives containing the pyrrolidine-2,4-dione moiety

（E）-Methyl-2-（2-（bromomethyl）phenyl）-3-methoxyacrylate was reacted with substituted 1-acetylpyr-rolidine-2,4-diones and 3-（1-（hydroxylamino）ethylidene）pyrrolidine-2,4-diones respectively to synthesize two series of/%methoxyacrylate derivatives containing the pyrrolidine-2,4-dione moiety. The structures of the targeted compounds were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. The fungicidal activity against Rhizoctonia solani, Botrytis cinerea and Fusarium graminearum was evaluated. The bioassay results demonstrated that these compounds showed visible fungicidal activity.

Synthesis, Biological Activity and 3D-QSAR Study of Novel Pyrrolidine-2,4-dione Derivatives Containing N-Substituted Phenylhydrazine Moiety

Twenty-seven novel pyrrolidine-2,4-dione derivatives containing N-substituted phenylhydrazine moiety were synthesized. Their structures were confirmed by IH NMR, 13C NMR and MS. The half effective concentration （ECs0） values of the title compounds against the phytopathogenic fungi Rhizoctonia cerealis were evaluated. Com- pounds 61 and 6q displayed good bioactivity with EC50 values of 1.626 and 2.043 μg/mL, respectively. The 3D quantitative structure activity relationship（3D-QSAR） model of CoMFA was established with reliable cross-validated correlation coefficient q2 value of 0.585 and Noncross-validated correlation coefficient r2 value of 0.971. This model provided a tool for guiding further design and synthesis of novel pyrrolidine-2,4-dione derivatives with high fungicidal activity.

Oxidative Rearrangement of Isatins with Arylamines Using H2O2 as Oxidant： A Facile Synthesis of Quinazoline-2,4-diones and Evaluation of Their Antibacterial Activity

A green and highly efficient synthetic method for the synthesis of quinazoline-2,4-diones with hydrogen peroxide as the terminal oxidant has been developed, The reaction features the mild reaction conditions, broad substrate scope, metal-free catalysts, and sole byproduct water. A plausible mechanism for this process was proposed. Moreover, an antibacterial activity study was performed to evaluate the antimicrobial activities towards two Gram-negative bacterial strains （Escherichia coli, and Klebsiella pneumonia） and two Gram-positive bacterial strains （Staphylococcus epidermidis, and Staphylococcus aureus） using the Broth microdilution method.

Multicomponent domino process for the synthesis of some novel 5-(arylidene)-3-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-thiazolidine-2,4-diones using PEG-400 as an efficient reaction medium and their antimicrobial evaluation

A series of novel thiazolidinedione-triazole hybrids were synthesized by one pot reaction between thiazolidine-2.4-dione,substituted aryl aldehydes,piopargyl bromide and substituted aryl azides using piperidine,CuSO4· 5H2O and sodium ascorbate as catalysts in PEG-400 as a highly efficient and green media.These thiazolidinedione-triazole hybrids were subjected to in vitro antibacterial activity against four strains namely.Staphylococcus aureus.Bacillus subtilis,Escherichia coli,Pseudomonas aeruginosa and antifungal activity against two fungal strains namely,Aspergillus niger and Aspergillus flavus.

A facile one-pot synthesis of new thieno-[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives

A facile one-pot synthesis of new 3-arylthieno[2,3-d]pyrimidine-2,4（1H,3H）-diones via base-catalyzed cyclocondensation of ethyl 2-amino-4,5-dimethylthiophene-3-carboxylate with aryl isocyanates is described.

Facile synthesis of[1,2,4]triazino[4,3-b][1,2,4,5]tetrazepin derivatives by a one-pot reactions using 4-amino-3-hydrazinyl-6-methyl-1,2,4-triazin-5(4H)-one

4-Amino-3-mercapto-6-methyl-l,2,4-triazin-5（4H）-one 1 converted to 4-amino-6-methy-3-（methylthio）-1,2,4-triazin-5（4H）-one by methylation with methyl iodide.Controlled hydrazination of the resulting compound afforded 4-amino-3-hydrazinyl-6- methyl-l,2,4-triazin-5（4H）-one 2 as a building block,to the synthesis of some novel derivatives of[1,2,4]triazino- [4,3,b][1,2,4,5]tetrazepine 3-6,by the reaction with 3-chloropentane-2,4-dione,chloro acetonitrile,1,3-dichloroacetone,and methyl bromoacetate.This general synthetic procedure can be extended to the preparation of wide variety of tetrazepines using 1,2- bielectrophiles derivatives.