Dimethyl Acetylenedicarboxylate Research Articles

Effect of Reactivity on Kinetics and a Mechanistic Investigation of the Reaction between Dimethyl Acetylenedicarboxylate and 1,3-Dicarbonyl Compounds in the Presence of a Catalyst: A Spectrophotometric Approach

A kinetic and mechanistic investigation, using conventional UV-Vis spectrophotometry, of the reaction between dimethyl acetylenedicarboxylate (DMAD) and 1,3-dicarbonyl compounds including acetylacetone (ACAC) and dibenzoylmethane (DBM), has been conducted in a methanol environment with triphenylarsine (TPA) acting as a catalyst. Previously, in a similar reaction, triphenylphosphine (TPP) (instead of TPA) had been employed as a reactant (not a catalyst) for the generation of an ylide (final product). In the present work, of significance is the differential behaviour of TPA which, as a catalyst in the reaction environment, leads to a cyclopropane compound. Of other significance is the different behaviours of the two reactants in the kinetics and mechanism of the reaction. In previous work, TPP acted as a weak nucleophile (a reactant), so the first step of the reaction was recognised as the rate-determining step (RDS). Here, TPA reacts as a stronger nucleophile and a catalyst, resulting in the fourth step of the reaction (step4, k4, a proton transfer process) being recognised as the RDS. The reaction followed second-order kinetics. The proposed mechanism was adapted in accord with the experimental results and the steady-state assumption. The results showed that the reaction rate decreases in the presence of DBM, which participates in the second step (step2), compared to ACAC when it is present as another 1,3-dicarbonyl compound (structural effect). In addition, in previous work, the partial order of the reaction with respect to the 1,3-dicarbonyl compound was zero, while it is one in the present work. As a significant result, not only did a change in the structure of one of the reactants (TPA instead of TPP) create a different product, but also the kinetics and reaction mechanism changed. In addition, the reaction is enthalpy-controlled.

Formation of the P–C and C–C bonds in the Reaction of 2-(5-Methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-4H-benzo[e]-1,3,2-dioxaphosphorin-4-one with Dimethyl Acetylenedicarboxylate under Mild Conditions

2-(5-Methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-4H-benzo[e]-1,3,2-dioxaphosphorin-4-one reacts under mild conditions with dimethyl acetylenedicarboxylate with the participation by only threecoordinated phosphorus atom and the formation of 2-(5-methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-3,4-dimethoxycarbonylbenzo[f]-1,2-oxaphosphepine-2,5-dione. During the process, simultaneous formation of the P–C and C–C bonds takes place.

Magnetic nanoparticles coated with a chitosan anchored Schiff base complex of nickel(II) as an effective, reusable catalyst for one-pot synthesis of spirolactones

A simple, highly versatile and efficient synthesis of spirolactones is achieved through the three components, one-pot reaction of 5-chloroisatin, different primary amines, and dimethyl acetylenedicarboxylate, using Fe3O4@CS-Schiff base Ni as a highly efficient heterogeneous catalyst. The catalyst can be recovered for subsequent reactions and reused for at least five rounds without any appreciable loss of activity. The core–shell structure and the composition of the magnetic nanocatalyst were characterized by physical and spectroscopic techniques.

Theoretical study on mechanism of reaction between tert-butyl isocyanide and dimethyl acetylenedicarboxylate in presence of ethanethiol or thiophenol

The mechanism of the multicomponent reaction between tert-butyl isocyanide and dimethyl acetylenedicarboxylate in presence of ethanethiol and thiophenol (as SH-acid) was investigated theoretically. According to quantum-mechanical computations, four different pathways (I, II, III, and IV) were predicted for this reaction. The potential energy of all structures participating along the different reaction paths was evaluated. Also, the geometry of all structures (including reactants, transition states, intermediates, and products) was optimized in gas phase to determine the best reaction path and most stable products. To verify the effect of solvent on the potential energy surfaces, dichloromethane and acetone were subjected to condensed-phase calculations using the polarizable continuum model. The theoretical results suggested a reasonable mechanism for each path, indicating that the first step of each pathway was rate determining. Finally, natural bond orbital analysis was applied for further understanding of the molecular interactions.

Platinum(iv) azido complexes undergo copper-free click reactions with alkynes.

We report our investigations into the first examples of copper-free 1,3-dipolar cycloaddition (click) reactions of electrophiles with a PtIV azido complex. The Pt-IV azido complex trans, trans, trans-[PtIV(py)2(N3)2(OH)2] (1) was reactive towards dimethyl acetylenedicarboxylate (DMAD) (2), diethyl acetylenedicarboxylate DEACD (3), N-[(1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonyl]-1,8-diamino-3,6-dioxaoctane (BCN) (11) and dibenzocyclooctyne-amine (DBCO) (12) resulting in formation of the corresponding mono (a) and bis-substituted (b) complexes. Complexes of 2 undergo further reactions between the Pt centre and the carbonyl group to form 2a' and 2b'. This is not seen for the products of the corresponding PtII azido complex trans-[Pt(py)2(N3)2] with acetylene 2. Novel complexes 2a', 2b', 11a and 11b have been characterised by multinuclear NMR, IR and UV-vis spectroscopy and ESI-MS. These reactions represent new synthetic routes to novel Pt(iv) complexes.

The Synthesis of 7-Substituted-2,3-dihydropyrido [4,3-d]pyridazine-1,4-diones and 1,4-Dioxo-7-substituted-1,2,3,4-tetrahydropyrido[4,3-d]pyridazine 6-Oxides from Methyl Ketones.

A general four-step transformation of alkyl, cycloalkyl, aryl, and heteroaryl methyl ketones via 3-(dimethylamino)-1-substituted-prop-2-en-1-ones, followed by microwave [2+2] cycloaddition of dimethyl acetylenedicarboxylate, cyclization of (2E,3E)-2-[(dimethylamino)methylene]-3-(2-substituted)succinates with ammonia or hydroxylamine hydrochloride into 2-substituted-pyridine-4,5-dicarboxylates and their N-oxides and final cyclization with hydrazine hydrate into of 7-substituted-2,3-dihydropyrido[3,4-d]pyridazine-1,4-diones and 1,4-dioxo-7-substituted-1,2,3,4-tetrahydropyrido[4,3-d]pyridazine 6-oxides is shown.

Theoretical Investigation of the Reaction Mechanism for a Type of N-heterocyclic Compound Involving Mono-N-aryl-3-aminodihydropyrrol

The kinetics of reaction between 4-methylaniline (1), dimethyl acetylenedicarboxylate (2) and formaldehyde (4) has been theoretically investigated to gain further insight into the reaction mechanism. The results of theoretical calculations were achieved using the ab initio method at the HF/6-311g (d, p) level of theory in gas phase. The mechanism of this reaction had 5 steps. Theoretical kinetic data (k and Ea), activation parameters (∆G#, ∆S# and ∆H#) and thermodynamic parameters (∆G, ∆S and ∆H) were calculated for each step and overall reaction. Step 2 of the mechanism was identified as the rate determining step. Also, the method of calculations was improved to B3LYP/6-311g (d, p) level of theory and the reaction mechanism was investigated for all steps of this reaction, again kinetic data and thermodynamic parameters were recalculated at this level of the theory. Improved data at this level was in a good agreement with the HF/6-311g (d, p) level of theory. Theoretical results, altogether were compatible with the literature's reports. As expected, step1 and step3 were recognized as the fast and fastest steps among the other steps. The overall reaction was enthalpy-controlled and proceeded chemically-controlled. In addition, step4 was recognized as a relatively slow, due to the five-membered ring formation in this step was inherently an energetically unfavorable.

Design, Synthesis, and Biological Evaluation of 1,4-Bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes as Potential Chk1 Inhibitors

A series of 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes were designed as inhibitors of checkpoint kinase 1 (Chk1), based on the structure‒activity relationships for known inhibitors through docking simulations. The docking results suggested that the title compounds were similar to known inhibitors in interaction with the catalytic site of Chk1. Twelve compounds were synthesized by a one-pot procedure from amines, dimethyl acetylenedicarboxylate, and glyoxal in water in the presence of catalytic amounts of γ-cyclodextrin. The inhibitory activities of the synthesized compounds were evaluated in vitro using EC9706 esophageal cancer cells. The results indicated that 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes significantly inhibited Chk1 (IC50 10.45 μM).

Synthesis and structure of a chiral areno-bridged [2.4]metacyclophane

The reductive coupling reaction of 1,4-bis(3-acetyl-5-tert-butyl-2-methoxyphenyl)butane 3 was carried out using TiCl4-Zn in pyridine followed by a McMurry coupling reaction to afford the compounds anti and syn 1,2-dimethyl[2.4]MCP-1-ene 4. Bromination of 4 with BTMA-Br3 in dry CH2Cl2 afforded the interesting compound 1,2-bis-(bromomethyl)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-1-ene 6 and consecutive debromination with Zn and AcOH in CH2Cl2 solution afforded the stable solid 5,15-di-tert-butyl-8,18-dimethoxy-1,2-dimethylene[2.4]MCP 7 in 89% yield. Compound 7 was conveniently employed in a Diels–Alder reaction with dimethyl acetylenedicarboxylate (DMAD) to provide 2-(3′,6′-dihydrobenzo)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-4′,5′-dimethylcarboxylate 8 in good yield. Diels–Alder adduct 8 was converted into a novel and inherently chiral areno-bridged compound [2.4]MCP 9 by aromatization. The chirality of the two conformers was characterized by circular dichroism (CD) spectra of the separated enantiomer which are perfect mirror images of each other.

Synthesis of a Phlorin from a Meso‐Fused Anthriporphyrin by a Diels–Alder Strategy

AbstractAn anthracene‐containing meso‐fused carbaporphyrin, which has extended π‐conjugation pathways as compared to the corresponding naphthalene‐containing carbaporphyrin, has been synthesized. The weak global aromaticity of the anthriporphyrin also allowed its use as the diene for a Diels–Alder reaction with dimethyl acetylenedicarboxylate (DMAD). The resulting phlorin contains an interesting bicyclic structure. Moreover, to the best of our knowledge, this phlorin is the first Diels–Alder adduct of a diene forming part of the global π‐conjugation pathway of an aromatic porphyrinoid.

Synthesis of a Phlorin from a Meso-Fused Anthriporphyrin by a Diels-Alder Strategy.

An anthracene-containing meso-fused carbaporphyrin, which has extended π-conjugation pathways as compared to the corresponding naphthalene-containing carbaporphyrin, has been synthesized. The weak global aromaticity of the anthriporphyrin also allowed its use as the diene for a Diels-Alder reaction with dimethyl acetylenedicarboxylate (DMAD). The resulting phlorin contains an interesting bicyclic structure. Moreover, to the best of our knowledge, this phlorin is the first Diels-Alder adduct of a diene forming part of the global π-conjugation pathway of an aromatic porphyrinoid.

One-pot synthesis of novel 3,10-dihydro-2H-1,3-oxazepino[7,6-b]indoles via 1,4-dipolar cycloaddition reaction

3,10-Dihydro-2H-1,3-oxazepino[7,6-b]indoles are synthesized via a convenient one-pot three-component 1,4-dipolar cycloaddition reaction, involving 3-alkyl(aryl)imidazo[1,5-a]pyridines, dimethyl acetylenedicarboxylate (DMAD) and N-alkylisatins. Structures of the newly synthesized heterocycles are evidenced from spectral data and further confirmed by single crystal X-ray diffraction. A plausible reaction mechanism is advanced, whereby the intermediate 1,4-dipole, generated in situ from imidazo[1,5-a]pyridine and DMAD, initially adds to the keto group of N-alkylisatins to form the corresponding 1,3-oxazin-spiro-oxindole cycloadduct. The latter undergoes subsequent unprecedented skeletal rearrangement through a cascade of bond breaking and bond making processes, eventually leading to ring enlargement, furnishing the tricyclic oxazepino[7,6-b]indole ring system as the end product.

An Organocatalytic Novel Synthesis of Polyfunctionalized Bis-2,5-dihydrofuran-3-carboxylates via Domino-MCR Strategy

For the first time, an elegant, metal-free and concise route using a pseudo five-component reaction of dimethyl acetylenedicarboxylate, mono/bis- aromatic aldehydes and amines with trifluoroacetic acid as an effective organocatalyst to afford novel and diverse substituted bis-2,5-dihydrofuran-3-carboxylates in good yields at ambient temperature has been described. The prominent features of this protocol are the energy sustainability, wide range of functional group tolerance, shorter reaction time, no column chromatographic purification, facile experimental and work-up procedure. The present one-step, cascade synthetic approach is straightforward that could avoid hazardous reagents/solvents and is turned to be a benign chemistry for the preparation of potent bis-O-heterocyclics on a multigram scale.

Generation and Trapping of Terminal Phosphinidene Complex [CF3P‐W(CO)5

AbstractThe LUMO of [CF3P−W(CO)5] is lower in energy than the LUMO of [ClP−W(CO)5] by 0.30 eV and [CF3P−W(CO)5] is the most electrophilic phosphinidene tungstenpentacarbonyl complex described so far. It is generated by reaction of dimethyl acetylenedicarboxylate with the appropriate 1‐trifluoromethylphosphole complex at 80 oC in toluene. It reacts normally with alkynes to give 1‐trifluoromethylphosphirene complexes. The reaction with alkenes works only with electron‐rich species. The phosphirane complexes appear to be unstable when electron‐poor C=C double bonds are used such as with trans‐stilbene. This highlights the importance of the P to C=C backbonding in the stability of the phosphirane adducts.

Crystal structure of methyl (Z)-2-[(Z)-3-methyl-2-({(E)-1-[(R*)-4-methyl-cyclo-hex-3-en-1-yl]ethyl-idene}hydrazinyl-idene)-4-oxo-thia-zolidin-5-yl-idene]acetate.

The new title 4-thia-zolidinone derivative, C16H21N3O3S, was obtained from the cyclization reaction of 4-methyl-3-thio-semicarbazone and dimethyl acetyl-enedi-carboxyl-ate (DMAD). The cyclo-hexyl-idene ring has an envelope conformation with the stereogenic centre C atom as the flap. Its mean plane makes a dihedral angle of 56.23 (9)° with the thia-zolidine ring mean plane. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds forming chains propagating in the [001] direction. Within the chains there are offset π-π inter-actions between the thia-zolidine rings of inversion-related mol-ecules [centroid-centroid distance = 3.703 (1) Å]. The chains are linked by further C-H⋯O hydrogen bonds, forming slabs parallel to the ac plane.

Synthesis of some new heterocycles containing quinazoline moiety

The presented herein synthesis of new quinazolines and quinazolino[3,4-a]quinazolines started from 2-amino-N-alkylbenzamides. Reaction of 2-amino-N-alkylbenzamides with 2-nitrobenzaldehyde followed by reduction using Zn afforded the corresponding 3-alkyl-2-(2-aminophenyl)-2,3-dihydroquinazolin-4(1H)-ones. Cyclization of the later compounds with carbon disulfide followed by methyl iodide, triethyl orthoformate or dimethyl acetylenedicarboxylate (DMAD) gave new quinazolino[3,4-a]quinazoline derivatives that were characterized on the basis of FT-IR, 1H, and 13C NMR spectra, and microanalytical data. In the case of reaction with DMAD, 2D nuclear Overhauser effect (2D-NOESY) spectrum together with comparison of the experimental and calculated chemical shifts at the B3LYP/6-311+G(d,p) level of theory were also used to identify the correct stereoisomer.

Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of annulated tetrahydrocarbazoles

Scaffolds of tetrahydrocarbazoles are an important class of biologically active compounds found abundant in nature. In the present investigation, functionalized polycyclic tetrahydrocarbazoles were synthesized using Diels-Alder cycloaddition between fused 5-, 6- and 7-membered ring 2-vinylindoles and various dienophiles. The dienophiles used were N-phenylmaleimides, 1,4-naphthoquinone, and dimethyl acetylenedicarboxylate (DMAD). When 1,4-naphthoquinone was used as a dienophile, the 5-membered ring Diels-Alder adduct was obtained in the oxidized form, but this form was not observed in the case of 6- and 7-membered ring Diels-Alder adducts. The desired product yields ranged from 60–70% and the structure of final compounds were determined using 1D and 2D NMR analysis. 1H NMR studies confirmed excellent diastereoselectivity (>99% de).

Construction of Spiropyrido[2, 1‐a]isoquinoline via Tandem Reactions of Huisgen's 1,4‐Dipoles with Various Alkene Dipolarophiles

AbstractThe three‐component reaction of isoquinoline, dimethyl acetylenedicarboxylate and arylidene pivaloylacetonitrile in acetonitrile at room temperature afforded pyrido[2, 1‐a]isoquinolines 1 a‐1 j in good yields and with high diastereoselectivity. When arylidene‐substituted 1,3‐indanediones, Meldrum acids, and N,N’‐dimethylbarbituric acids were employed in the reaction, the novel functionalized spiro[indene‐2, 1′‐pyrido[2, 1‐a]isoquinolines] 2 a‐2 j, spiro[pyrido[2, 1‐a]isoquinoline‐1,5′‐[1, 3]dioxanes] 3 a‐3 h and spiro[pyrido[2, 1‐a]isoquinoline‐1,5′‐pyrimidines] 4 a‐4 e were also efficiently synthesized in satisfactory yields. The reaction mechanism included domino formation of Huisgen's 1,4‐dipole, Michael addition and cyclization processes.

Three-Component Reaction of Benzothiazole, Acetylenic Esters, Phenoles; Synthesis of Dialkyl 2-benzo[d]thiazol Derivatives Under Grinding.

Due to biological activity of a significant number of compounds containing benzothiazole ring system and in continuation of our interest in developing new environmentally benign methods for the synthesis of heterocyclic compounds by MCRs in this study we performed an efficient three-component from benzothiazole, acetylenic esters and hydroxyl aromatics compounds to synthesize of 2- benzothiazole derivatives in high yield. IR spectra were recorded using an FTIR apparatus. Melting points measured on an Electrothermal 9100 apparatus. Spectra were obtained in solution of CDCl3 using TMS as internal standard. Elemental analyses were carried out using a Heracus CHN-O- Rapid analyzer. A mixture of benzothiazole, dimethyl acetylenedicarboxylate and phenol were placed in a mortar. The mixture was ground with a mortar and pestle at room temperature for 12 min. After completion of the reaction, as indicated by TLC (ethyl acetate: n-hexane, 1: 3), the solvent was distilled off under reduced pressure and the residue was crystallized from diethyl ether. Treatment of benzothiazole and dialkyl acetylenedicarboxylates in presence of resorcinol and β-naphthol led to products 4 (dialkyl (E)-2-(2-(2-hydroxyphenyl)benzo[d]thiazol-3(2H)-yl-3- methylbut-2-enedioate), while we observed two isomer (Z) and (E) configurations (major and minor) in nearly 70:30 ratio when the reaction was repeated in presence of 8-hydroxy quinolone and DMAD. Also when we examined 2-nitro phenol, 4-nitrophenol, and 4-hydroxy quinoline, only one product 5 was obtained. This indicates that the reaction proceeds efficiently with electron-releasing substituted phenols. The reaction between benzothiazole and dialkyl acetylenedicarboxylates in the presence of some phenols without electron-withdraw substitution, presents a novel, one-pot, clean, convenient, simple and inexpensive approach into the synthesis of 2-benzothiazole derivatives of potential synthetic and pharmacologically interest. This procedure carries significant advantages because of the minimization of labor, time, and cost.

Synthesis of 4,4′-(arylmethylene)bis(3-carboxymethyl-1-phenyl-1H-pyrazol-5-ol)s using ionic liquid attached to colloidal silica nanoparticles in water

An efficient synthesis of 10 4,4′-(arylmethylene)bis(3-carboxymethyl-1-phenyl-1 H-pyrazol-5-ol)s, eight of which are novel, was achieved by a one-pot three-component reaction of phenylhydrazine, dimethyl acetylenedicarboxylate and an arylaldehyde using bis(1(3-methoxysilylpropyl)-3-methyl-imidazolium) copper tetrachloride tethered to colloidal silica nanoparticles as catalyst under microwave irradiation in water. The advantages of the present process are atom economy, high catalytic activity, excellent yields, short reaction times and utilisation of microwave heating as a clean procedure. The catalyst was recyclable.