6-Alkynylpurines bearing electronacceptor substituents: Preparation, reactivity in cycloaddition reactions and cytostatic activity

2011 ◽  
Vol 76 (12) ◽  
pp. 1487-1527 ◽  
Author(s):  
Martin Křováček ◽  
Hana Dvořáková ◽  
Ivan Votruba ◽  
Ivana Císařová ◽  
Dalimil Dvořák
Keyword(s):  
Cycloaddition Reaction ◽  
Cytostatic Activity ◽  
Cycloaddition Reactions ◽  
Sonogashira Coupling ◽  
Phenyl Substituent ◽  
Ethynyl Group ◽  
Methyl Propiolate

While direct Sonogashira coupling of 6-halopurines with methyl propiolate and with propargyl aldehyde was not successful, the corresponding orthoester and propargyl aldehyde diethylacetal reacted smoothly. Such prepared orthoester was then converted to the desired methylester by methanolysis, the acetal was too stable to be hydrolyzed. The obtained 6-ethynylpurines, bearing orthoester, acetal, methoxycarbonyl and for comparison also the phenyl substituent on the ethynyl group, were subjected to the cycloaddition reaction with cyclopentadiene, diazomethane and phenylazide. Electron deficient alkynylpurines were considerably more reactive in this reaction compared to the not activated phenylethynyl derivative. The prepared alkynylpurines exhibited medium cytostatic activity (IC50 = 2.6–15 μM), while the cycloadducts were inactive.

scholarly journals Huisgen [3 + 2] Dipolar Cycloadditions of Phthalazinium Ylides to Activated Symmetric and Non-Symmetric Alkynes

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4416
Author(s):  
Vasilichia Antoci ◽  
Costel Moldoveanu ◽  
Ramona Danac ◽  
Violeta Mangalagiu ◽  
Gheorghita Zbancioc
Keyword(s):  
Reaction Time ◽  
Comparative Study ◽  
Cycloaddition Reaction ◽  
Environmentally Friendly ◽  
Dipolar Cycloaddition ◽  
Cycloaddition Reactions ◽  
Dimethyl Acetylenedicarboxylate ◽  
Thermal Heating ◽  
Dipolar Cycloadditions ◽  
Methyl Propiolate

We present herein a straightforward and efficient pathway for the synthesis of pyrrolophthalazine cycloadducts via Huisgen [3 + 2] dipolar cycloaddition reactions of phthalazinium ylides to methyl propiolate or dimethyl acetylenedicarboxylate (DMAD). A thoroughly comparative study concerning the efficiency of synthesis, conventional thermal heating (TH) versus microwave (MW) and ultrasound (US) irradiation, has been performed. The cycloaddition reactions of phthalazinium ylides to methyl propiolate occur regiospecific, with a single regioisomer being obtained. Under conventional TH, the cycloaddition reaction of phthalazinium ylides with DMAD occurs to a mixture of inseparable partial and fully aromatized pyrrolophthalazine cycloadducts, while MW or US irradiation are leading only to fully aromatized compounds, with the reactions becoming selective. A feasible mechanism for formation of fully aromatized compounds is presented. Besides selectivity, it has to be noticed that the reaction setup under MW or US irradiation offer a number of other certain advantages: higher yields, decreasing of the amount of used solvent comparative with TH, decreasing of the reaction time from hours to minutes and decreasing of the consumed energy; consequently, these reactions could be considered environmentally friendly.

scholarly journals Preparation and Identification of Novel 1, 3-Oxazepine Derivatives by Cycloaddition Reactions [2+5] of Selected Carboxylic Acid Anhydrides with Imines Derived from 4-methyl aniline

2018 ◽  
Vol 29 (2) ◽  
pp. 93 ◽  
Author(s):  
Obaid H. Abid ◽  
Ahmed Khames Ramadan
Keyword(s):  
Carboxylic Acid ◽  
Physical Properties ◽  
Spectral Data ◽  
1H Nmr ◽  
Cycloaddition Reaction ◽  
Absolute Ethanol ◽  
Cycloaddition Reactions ◽  
Thermal Condensation ◽  
Ft Ir ◽  
Acid Anhydrides

Novel 1,3-oxazepine derivatives have been synthesis via (2+5) cycloaddition reaction of imines and selected cyclic carboxylic acid anhydrides by refluxing in dry benzene. Imines have been prepared by thermal condensation of 4-methyl aniline and para substituted benzaldehyde in absolute ethanol under reflux conditions. The structure of the target compounds were Identified by some physical properties and spectral data of FT-IR and 1H-NMR.

scholarly journals Enhancing the reactivity of 1,2-diphospholes in cycloaddition reactions

2015 ◽  
Vol 11 ◽  
pp. 169-173 ◽  
Author(s):  
Almaz Zagidullin ◽  
Vasili Miluykov ◽  
Elena Oshchepkova ◽  
Artem Tufatullin ◽  
Olga Kataeva ◽  
...  
Keyword(s):  
Room Temperature ◽  
Cycloaddition Reaction ◽  
Alder Reaction ◽  
Diels Alder ◽  
Alkyl Halides ◽  
Ethyl Iodide ◽  
Para Position ◽  
Cycloaddition Reactions ◽  
Diels Alder Reaction ◽  
Heating Up

Two different approaches have been employed to enhance the reactivity of 1-alkyl-1,2-diphospholes – the introduction of electron-withdrawing groups either at the phosphorus atoms or in the para-position of the arene ring. The alkylation of sodium 1,2-diphospha-3,4,5-triphenylcyclopentadienide with alkyl halides Hal-CH2-R (R = CN, COOEt, OMe, CH2OEt) results in corresponding 1-alkyl-3,4,5-triphenyl-1,2-diphospholes (alkyl = CH2CN (1a), CH2COOEt (1b), CH2OMe (1c), and (CH2)2OEt (1d)), which spontaneously undergo the intermolecular [4 + 2] cycloaddition reactions at room temperature to form the mixture of the cycloadducts, 2a–c, respectively. However the alkylation of sodium 1,2-diphospha-3,4,5-tri(p-fluorophenyl)cyclopentadienide with ethyl iodide leads to stable 1-ethyl-3,4,5-tris(p-fluorophenyl)-1,2-diphosphole (1e), which forms the [4 + 2] cycloadduct 2,3,4,4a,5,6-hexa(p-fluorophenyl)-1-ethyl-1,7,7a-triphospha-4,7-(ethylphosphinidene)indene (2e) only upon heating up to 60 °C. With further heating to 120 °C with N-phenylmaleimide, the cycloadducts 2a–c and 2e undergo the retro-Diels–Alder reaction and form only one product of the [4 + 2] cycloaddition reaction 3a–с, 3e with good yields up to 65%.

Spiroheterocycles via Regioselective Cycloaddition Reactions of Nitrile Oxides with 5-Methylene-1H-pyrrol-2(5H)-ones

2010 ◽  
Vol 63 (3) ◽  
pp. 445 ◽  
Author(s):  
Nicola J. Beattie ◽  
Craig L. Francis ◽  
Andris J. Liepa ◽  
G. Paul Savage
Keyword(s):  
Cycloaddition Reaction ◽  
Biphasic System ◽  
Dipolar Cycloaddition ◽  
Cycloaddition Reactions ◽  
Nitrile Oxides ◽  
Facial Selectivity

Substituted 5-methylene-1H-pyrrol-2(5H)-ones underwent a 1,3-dipolar cycloaddition reaction with nitrile oxides to give the corresponding spiro heterocycles. Critical to this reaction was the development of a biphasic system for base-induced dehydrohalogenation of hydroximoyl chlorides, to give nitrile oxides, in the presence of a base-sensitive dipolarophile. A substituted N-tolyl 5-methylene-1H-pyrrol-2(5H)-one exhibited atropisomerism, which in turn led to a 4:1 facial selectivity during cycloaddition.

Synthesis of Optically Active 2,3-Disubstituted Indoline ­Derivatives through Cycloaddition Reactions between Benzynes and α,β-Unsaturated γ-Aminobutyronitriles

Synlett ◽  
2018 ◽  
Vol 29 (04) ◽  
pp. 530-536 ◽  
Author(s):  
Takashi Ikawa ◽  
Shuji Akai ◽  
Yuta Sumii ◽  
Shigeaki Masuda ◽  
Ding Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cycloaddition Reaction ◽  
Optically Active ◽  
Amino Acid Derivatives ◽  
Cycloaddition Reactions

We report a method for synthesizing optically active 2,3-disubstituted indolines by the cycloaddition reaction of benzynes with various 4-[(4-toluenesulfonyl)amino]-(E)-but-2-enenitriles, which are readily prepared from the corresponding l-amino acid derivatives.

Gold-catalyzed generation of vinylthionium ions and the development of an organocatalytic, asymmetric (4+3)-cycloaddition reaction

2017 ◽  
Author(s):  
◽  
Michael Topinka
Keyword(s):  
Amino Alcohol ◽  
Good Yield ◽  
Lewis Acids ◽  
Cycloaddition Reaction ◽  
Unsaturated Ester ◽  
Cycloaddition Reactions ◽  
University Of Missouri ◽  
Considerable Problem ◽  
The University ◽  
Substituted Furans

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] An allylic benzoate ester was prepared and used as a progenitor of vinylthionium ions for (4+3)-cycloaddition reactions. The chemistry was limited to 2-substituted and 2,5-disubstituted furans. In the case of 2-substituted furans, only Friedel-Crafts alkylation products were procured. In the case of 2,5-disubstituted furans, (4+3)-cycloaddition products were furnished in good yield. A catalytic, asymmetric variant using 2,5-dialkylfurans and chiral acids to procure cycloaddition products was unsuccessful. There was an opportunity to overcome the Friedel-Crafts alkylation problem that arose in a gold-catalyzed cycloaddition project. A sulfur-substituted unsaturated ester and alcohol were prepared, but silyl migration was a considerable problem upon activation by various agents. The problem of silyl migration was circumvented, but the target aldehyde was unreactive toward dienes in the presence of various Lewis acids. In further pursuit of an asymmetric (4+3)-cycloaddition reaction, 2-substituted furans were reacted with 2-tosyloxycyclopentanone in the presence of K2HPO4/H2O in perfluorobenzene as solvent and 30 mol% of an amino alcohol catalyst developed by David MacMillan. Enantioselectivities were modest for 2-alkylfurans and excellent for 2-arylchalcogenofurans (90% ee). 3-Substituted furans also work in this process.

scholarly journals Ab initio study of mechanism of forming a Si-heterocyclic spiro-Sn-heterocyclic ring compound by cycloaddition reaction of Me2Si=Sn: and ethene

2019 ◽  
Vol 44 (2) ◽  
pp. 114-121
Author(s):  
Xiaojun Tan ◽  
Xiuhui Lu
Keyword(s):  
Singlet State ◽  
Cycloaddition Reaction ◽  
Chemical Species ◽  
Heterocyclic Ring ◽  
Basis Set ◽  
Cycloaddition Reactions ◽  
Unoccupied Orbital ◽  
Donor Acceptor ◽  
Moller Plesset ◽  
First Time

X2Si=Sn: (X = H, Me, F, Cl, Br, Ph, Ar, etc.) are a new chemical species. The cycloaddition reactions of X2Si=Sn: are a new field of stannylene chemistry. The mechanism of the cycloaddition reaction between singlet state Me2Si=Sn: and ethene has been investigated for the first time here using second-order Møller-Plesset perturbation theory together with the 6-311++G** basis set for C, H and Si atoms and the LanL2dz basis set for Sn atoms. From the potential energy profile, it could be predicted that the reaction has one dominant reaction channel. The reaction process presented is that the 5p unoccupied orbital of Sn in Me2Si=Sn: and the π orbital of ethene form a π → p donor–acceptor bond resulting in the formation of an intermediate. The instability of this intermediate makes it isomerize to a four-membered Si-heterocyclic ring stannylene. Because the 5p unoccupied orbital of the Sn atom in the four-membered Si-heterocyclic ring stannylene and the π orbital of ethene form a π → p donor–acceptor bond, the four-membered Si-heterocyclic ring stannylene further combines with ethene to form another intermediate. Because the Sn atom in this intermediate assumes sp3 hybridization after the transition state, the intermediate isomerizes to a Si-heterocyclic spiro-Sn-heterocyclic ring compound. This result indicates the modes of cycloaddition reactions between X2Si=Sn: and symmetric π-bonded compounds, i.e. this study opens up a new field for stannylene chemistry.

scholarly journals Enantioselective 1,3-Dipolar Cycloaddition Reaction of Nitrones with α-(Acyloxy)acroleins Catalyzed by Dipeptide-Derived Chiral Tri- or Diammonium Salts

Synlett ◽  
2019 ◽  
Vol 30 (15) ◽  
pp. 1835-1839 ◽  
Author(s):  
Chihiro Kidou ◽  
Haruki Mizoguchi ◽  
Tatsuo Nehira ◽  
Akira Sakakura
Keyword(s):  
Cycloaddition Reaction ◽  
Dipolar Cycloaddition ◽  
Cycloaddition Reactions ◽  
Reaction Conditions

Organoammonium salts of dipeptide-derived chiral triamines or diamines with TfOH catalyzed the enantioselective 1,3-dipolar cycloaddition reactions of α-acyloxyacroleins with nitrones to give the corresponding adducts in good yields (up to 96%) and with high diastereo- and enantioselectivities (up to 89% ee). Although α-(p-methoxybenzoyloxy)acrolein is rather unstable under the reaction conditions, α-(3-pyrroline-1-carbonyloxy)acrolein is stable enough to be smoothly converted into the corresponding adducts with the aid of the chiral organoammonium salt catalysts.

scholarly journals On the Question of Zwitterionic Intermediates in the [3 + 2] Cycloaddition Reactions between C-arylnitrones and Perfluoro 2-Methylpent-2-ene

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7147
Author(s):  
Katarzyna Mitka ◽  
Katarzyna Fela ◽  
Aleksandra Olszewska ◽  
Radomir Jasiński
Keyword(s):  
Dft Calculations ◽  
Molecular Mechanism ◽  
Intermolecular Interactions ◽  
Cycloaddition Reaction ◽  
Reaction Centers ◽  
Cycloaddition Reactions ◽  
Reaction Paths ◽  
One Step ◽  
Step Mechanism

The molecular mechanism of the [3 + 2] cycloaddition reaction between C-arylnitrones and perfluoro 2-methylpent-2-ene was explored on the basis of DFT calculations. It was found that despite the polar nature of the intermolecular interactions, as well as the presence of fluorine atoms near the reaction centers, all reactions considered cycloaddition proceed via a one-step mechanism. All attempts for the localization of zwitterionic intermediates on the reaction paths were not successful. Similar results were obtained regardless of the level of theory applied.

Sign in / Sign up

Export Citation Format

Share Document