Diethyl Methylmalonate Research Articles

4,4′-(Butane-1,4-diyl)bis(4-methyl-1,2-dioxolane-3,5-dione)

Over the past decades, studies of cyclic diacyl peroxides have shown superior or even fundamentally new reactivity compared to their acyclic counterparts in various reactions. Previously, the scope of cyclic diacyl peroxides was limited to the mono peroxy compounds. The first doubled cyclic diacyl peroxide is presented herein. The diperoxide was characterized by NMR spectroscopy, mass spectrometry, and IR spectroscopy. The structure of 4,4′-(butane-1,4-diyl)bis(4-methyl-1,2-dioxolane-3,5-dione) was confirmed by X-ray diffraction analysis. The novel diperoxide was prepared in a 55% overall yield in three steps from dibromobutane and diethyl methylmalonate.

Synthesis, Characterization, Solution Behavior and Theoretical Studies of Pd(II) Allyl Complexes with 2-Phenyl-3H-indoles as Ligands

The study of the reactivity of three 2-phenyl-3H-indole ligands of general formulae C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2 (1) [with R1 = H, R2 = OMe (a); R1 = R2 = H (b) or R1 = Cl, R2 = H (c)] with [Pd(η3-1-R3C3H4)(μ-Cl)]2 (R3 = H or Ph) has allowed us to isolate two sets of new Pd(II)-allyl complexes of general formulae [Pd(η3-1-R3C3H4)(1)Cl] {R3 = H (2) or Ph (3)}. Compounds 2a–2c and 3a–3c were characterized by elemental analyses, mass spectrometry and IR spectroscopy. The crystal structures of 2a, 3a and 3b were also determined by X-ray diffraction. 1H-NMR studies reveal the coexistence of two (for 2a–2c) or three (for 3a–3c) isomeric forms in CD2Cl2 solutions at 182 K. Additional studies on the catalytic activity of mixtures containing [Pd(η3-C3H5)(μ-Cl)]2 and the parent ligand (1a–1c) in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate as well as the stoichiometric reaction between compounds 3a and 3c with the nucleophile reveal that in both cases the formation of the linear trans- derivative is strongly preferred over the branched product. Computational studies at a DFT level on compound 3a allowed us to compare the relative stability of their isomeric forms present in solution and to explain the regioselectivity of the catalytic and stoichiometric processes.

Anionic Polymerization of Methylene Malonate for High-Performance Coatings

Here, we demonstrate the anionic polymerization and the high reactivity of the novel monomer diethyl methylene malonate (DEMM). At room temperature and under atmospheric conditions, water and anionic functional groups (i.e., carboxyl, boronic, and phenol) quickly initiate DEMM. The polymerization of DEMM in water and the final molecular weight of the polymer were both demonstrated to be pH-dependent. Systematically, investigations were conducted to study the conversion rate of DEMM with various functional groups, and the polymerization was verified to occur with anionic groups using a carboxylate-initiated DEMM system. For coating applications, we also investigated a multifunctional derivative monomer called (DEMM)6 that is an oligomeric polyester of DEMM esterified with butanediol that contains on average six repeat units of reactive DEMM (commercially known as Forza B3000 XP). The incorporation of 15 wt % (DEMM)6 into latex containing methacrylate acid as a functional monomer yielded cross-linked coatings with a gel content of 76.25 wt % that had a 289% improvement in rub-resistance performance compared to controls (without (DEMM)6). This study provides a facile methodology to synthesize cross-linked latex coatings at room temperature.

DFT study on α-regioselectivity of photo-organocatalytic functionalization of aldehydes

Density functional theory (DFT) study has been conducted to elucidate the key mechanistic transformations and the unique α-regioselectivity of alkylidene malonates towards the photoinitiated α-alkylation of aldehydes. The reaction between n-butyl aldehyde and diethyl methylenemalonate was chosen as model reaction and the possible reaction pathways were computed. Our calculations reveal that α-alkylation of aldehydes with alkylidene malonates proceeds through a radical–radical coupling pathway, instead of the radical chain or radical propagation pathway. This work demonstrates the details of the mechanistic framework and rationalizes the α-regioselectivity of alkylidene malonates.

A practical chemoenzymatic synthesis of (R)-isovaline based on the asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide

(R)-Isovaline has potential applications in drug development, and therefore the development of an efficient method for the production of (R)-isovaline is desired. Herein we have investigated the asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide into (S)-2-ethyl-2-methyl-malonamic acid, a useful synthetic intermediate in the production of (R)-isovaline, using CsAM, which is a recombinant amidase originally derived from Cupriavidus sp. KNK-J915. The produced (S)-2-ethyl-2-methyl-malonamic acid (98.6% ee) could be easily converted into (R)-isovaline by the Hofmann rearrangement. Starting from diethyl 2-methylmalonate, we obtained (R)-isovaline (99.1% ee) in 58.6% yield over eight steps, including the CsAM-catalyzed asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide.

An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain

The Saccharopolyspora erythraea mutB knockout strain, FL2281, having a block in the methylmalonyl-CoA mutase reaction, was found to carry a diethyl methylmalonate-responsive (Dmr) phenotype in an oil-based fermentation medium. The Dmr phenotype confers the ability to increase erythromycin A (erythromycin) production from 250-300% when the oil-based medium is supplemented with 15 mM levels of this solvent. Lower concentrations of the solvent stimulated proportionately less erythromycin production, while higher concentrations had no additional benefit. Although the mutB strain is phenotypically a low-level erythromycin producer, diethyl methylmalonate supplementation allowed it to produce up to 30% more erythromycin than the wild-type (control) strain-a strain that does not show the Dmr phenotype. The Dmr phenotype represents a new class of strain improvement phenotype. A theory to explain the biochemical mechanism for the Dmr phenotype is proposed. Other phenotypes found to be associated with the mutB knockout were a growth defect and hyper-pigmentation, both of which were restored to normal by exposure to diethyl methylmalonate. Furthermore, mutB fermentations did not significantly metabolize soybean oil in the presence of diethyl methylmalonate. Finally, a novel method is proposed for the isolation of additional mutants with the Dmr phenotype.

Substituent effects of accelerator on nitroxide-mediated radical polymerization

The acceleration effect of various agents on the rate of styrene bulk polymerization in 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) mediated polymerization was investigated, including dimethyl malonate (DMM), diethyl methyl malonate (DEMM), diethyl tert-butylmalonate (DEBM), diethyl diethylmalonate (DEDEM), 3-methyl-2,4-pentanedione (MPD), acetyl malononitrile (Ac-MN), and dimethyl malononitrile (DM-MN). Polymerization with the additive proceeded in a living manner, as indicated by keeping a low polydispersity and increasing the molecular weight with the reaction time and conversion. The structure of the styrene polymerization did not change in the presence of these additives. The monomer conversion efficiency was approximately 99% and maintained a relatively narrow polydispersity of 1.29 with the optimal [Ac-MN]/[TEMPO] molar ratios of 4 in 1.5 h. With the accelerator, dipole/dipole interactions led to a weakening of the C-ON bond and an acceleration of the reaction. There is a trend for a higher polymerization rate with more electron-withdrawing substituents.

ChemInform Abstract: Copper-Promoted Reaction of Aryl Iodides with Activated Methine Compounds.

The reaction of aryl iodides with an activated methine compound, diethyl acetamidomalonate, can efficiently proceed in the presence of CuI and NaH in DMSO to give diethyl acetamido(aryl)malonates, which may be useful precursors for α-arylglycines, in good yields. Although the reaction with another methine substrate, ethyl 2-cyanopropionate, also affords the expected coupling products, no substitution products are obtained in the case of diethyl methylmalonate, arenes together with an oxidative coupling compound of the ester being formed.

Chelate-Size Effects on the Structures, Chemical Behavior, Properties, and Catalytic Activity of the New Palladium(II)−Allyl Complexes [Pd(η3-1-R1-C3H4){FcCH═N-CH2-(CH2)n-NMe2}][PF6] {Fc = (η5-C5H5)Fe(η5-C5H4), n = 2 or 1, and R1 = H or Ph}

The synthesis, X-ray crystal structures, and the study of the solution behavior of the palladium(II) allyl complexes [Pd(η3-1R1-C3H4){FcCH═N-CH2-(CH2)n-NMe2}][PF6] {with Fc = (η5-C5H5)Fe(η5-C5H4), R1 = H, and n = 2 (4) or 1 (5) or R1 = Ph and n = 2 (6) or 1 (7)} are described. The structural studies of 4, 5, 6, and 7 showed that the allyl ligands were bound to palladium(II) in an η3-fashion and the ferrocenyl-Schiff bases behaved as neutral (N,N′) bidentate ligands. As observed for other Pd complexes of ligands 1 and 2, the imine conformation of the ligand in the complex strongly depends on the length of the hydrocarbon chain between the two nitrogen donors: compounds 4 and 6 exhibited an anti-(E) conformation, whereas the syn-(Z) form is observed in 5 and 7. 57Fe-Mössbauer spectra (in the solid state) and electrochemical studies based on cyclic voltammetry of 4, 5, 6, and 7 are reported. These studies reveal that the proclivity of the iron(II) toward oxidation is affected by the nature of the substituent R1 of the allyl group {H (in 4 and 5) or Ph (in 6 and 7)}. Compounds 4 and 5 have been tested in the palladium(II) allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate using sodium diethyl 2-methylmalonate as the nucleophile. In all cases the formation of the trans-(E) isomer of the linear product (9) was strongly favored versus that of the branched derivative (10). The stoichiometric reactions of the palladium(II) allyl intermediates [Pd(η3-1-Ph-C3H4){FcCH═N-CH2-(CH2)n-NMe2}][PF6] {with n = 2 (6) or 1 (7)} with the nucleophile have been studied. Density functional theory (DFT) calculations of these systems have allowed us to rationalize the structural differences as well as the regioselectivity of the catalytic and stoichiometric reactions.

Iron‐Catalyzed Nucleophilic Substitution of Allylic Acetate

AbstractThe combination of diiron nonacarbonyl and dimethylamine gives an active catalyst for displacement of allylic acetate by diethyl methylmalonate. It was found that among a series of amines, only dimethylamine and morpholine were efficient promoters of the reaction. Solvents such as dimethylformamide (DMF) and N‐methylformamide were much superior to tetrahydrofuran, dichloromethane, and ethanol.

Schiff bases containing ferrocenyl and thienyl units and their utility in the palladium catalyzed allylic alkylation of cinnamyl acetate

The synthesis and characterization of two new ferrocenyl Schiff bases: [Fc-CH N–(CH 2) n –(C 4H 3S)] ( 2) {Fc represents (η 5-C 5H 5)Fe(η 5-C 5H 4)– and n = 1( 2a) or 2( 2b)} containing the thienyl (C 4H 3S) group are reported. NMR studies indicate that 2 have the anti-( E) conformation in solution and the X-ray crystal structure of 2a confirms that it also adopts the anti-( E) form in the solid state. Ligands 2 have been tested in the palladium catalyzed allylic alkylation of ( E)-3-phenyl-2-propen-1-yl ( cinnamyl) acetate using sodium diethyl 2-methylmalonate as nucleophile. The reaction of 2 with [Pd(η 3-1-Ph–C 3H 4)(μ-Cl)] 2 in the presence of a slight excess K[PF 6] produced [Pd(η 3-1-Ph–C 3H 4){Fc-CH N–(CH 2) n -(C 4H 3S)}][PF 6] { n = 1( 5a) or 2( 5b)}, which are the intermediates of this catalytic process. NMR studies of 5 reveal the coexistence of several isomers in solution. The stoichiometric reactions of 5 with the nucleophile are also reported. The comparison of the results obtained for 2, [Fc-CH N–(C 6H 4–2SMe)] ( 1a) and [(2,4,6-Me 3-C 6H 2)–CH N–(C 6H 4–2SMe)] ( 1b) has allowed to establish the importance of the nature of the substituents on the imine group on the regioselectivity of the process.

Palladium(II)–allyl complexes containing chiral N-donor ferrocenyl ligands

A study of the reactivity of enantiopure ferrocenylimine ( S C )-[FcCH N–CH(Me)(Ph)] {Fc = (η 5-C 5H 5)Fe{(η 5-C 5H 4)–} ( 1a) with palladium(II)–allyl complexes [Pd(η 3-1R 1,3R 2-C 3H 3)(μ-Cl)] 2 {R 1 = H and R 2 = H ( 2), Ph ( 3) or R 1 = R 2 = Ph ( 4)} is reported. Treatment of 1a with 2 or 3 {in a molar ratio Pd(II): 1a = 1} in CH 2Cl 2 at 298 K produced [Pd(η 3-3R 2-C 3H 4){FcCH N–CH(Me)(Ph)}Cl] {R 2 = H ( 5a) or Ph ( 6a)}. When the reaction was carried out under identical experimental conditions using complex 4 as starting material no evidence for the formation of [Pd(η 3-1,3-Ph 2-C 3H 3){FcCH N–CH(Me)(Ph)}Cl] ( 7a) was found. Additional studies on the reactivity of ( S C )-[FcCH N–CH(R 3)(CH 2OH)] {R 3 = Me ( 1b) or CHMe 2 ( 1c)} with complex 4 showed the importance of the bulk of the substituents on the palladium(II) allyl–complex ( 2– 4) or on the ferrocenylimines ( 1) in this type of reaction. The crystal structure of 5a showed that: (a) the ferrocenylimine adopts an anti-( E) conformation and behaves as an N-donor ligand, (b) the chloride is in a cis-arrangement to the nitrogen and (c) the allyl group binds to the palladium(II) in a η 3-fashion. Solution NMR studies of 5a and 6a and [Pd(η 3-1,3-Ph 2-C 3H 3){FcCH N–CH(Me)(CH 2OH)}Cl] ( 7b) revealed the coexistence of several isomers in solution. The stoichiometric reaction between 6a and sodium diethyl 2-methylmalonate reveals that the formation of the achiral linear trans-( E) isomer of Ph–CH CH–CH 2Nu ( 8) was preferred over the branched derivative ( 9). A comparative study of the potential utility of ligand 1a, complex 5a and the amine ( S C )-H 2N–CH(Me)(Ph) ( 11) as catalysts in the allylic alkylation of ( E)-3-phenyl-2-propenyl ( cinnamyl) acetate with the nucleophile diethyl 2-methylmalonate (Nu −) is reported.

Modular Synthesis of a New Family of Tripodal Ligands, all-cis-1,2,3-Tris(diphenylphosphinomethyl)cyclopropane and Relatives

Bisbenzyl-protected all-cis-1,2,3-tris(hydroxymethyl)cyclopropane has been obtained in three steps from commercially available cis-2-butene-1,4-diol (75% overall yield) and used to prepare a number of all-cis-1,2,3-trisubstituted cyclopropane derivatives. Among them, the new tripodal ligand all-cis-tris(diphenylphosphinomethyl)cyclopropane (TriCyp-PPP) has been demonstrated to furnish-with pi-allylpalladium chloride dimer-a highly active catalyst for the allylation of diethyl methylmalonate enolate with allyl acetate.

Heterodimetallic Palladium(II) Complexes with Bidentate (N,S) or Terdentate (C,N,S)- Ferrocenyl Ligands. The Effect of the Ligand Donor Atoms on the Regioselectivity of the Allylic Alkylation of Cinnamyl Acetate

The synthesis and characterization of [Pd(η3-1-R1-C3H4){FcCHN−(C6H4−2SMe)}][PF6] {R1 = H (2a) or Ph (3a)} are described. A comparative study of the catalytic activity of (a) the mixtures containing [Pd(η3-C3H5)(μ-Cl)]2 and its parent ligand (1a) or H2N−C6H4−2SMe (4) and (b) the palladacycles [Pd{[(η5-C5H3)−CHN−(C6H4−2SMe)]Fe(η5-C5H5)}Cl] (5a), [Pd{(2-CH2-4,6-Me2C6H2)−CHN−(C6H4−2SMe)}Cl] (5b) in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate is also reported.

NMR Spectroscopy and MALDI‐TOF MS Characterisation of End‐Functionalised PVP Oligomers Prepared with Different Esters as Chain Transfer Agents

Ester-functionalised poly(1-vinylpyrrolidin-2-one) (PVP) oligomers obtained by radical polymerisation in methyl propionate, diethyl malonate and diethyl 2-methylmalonate were characterised by NMR spectroscopy, and MALDI-TOF mass spectrometry. The chain-transfer constants were determined as 5.54 x 10(-4), 1.22 x 10(-3) and 1.70 x 10(-2), respectively, by measuring the variation of the number-average molecular weight on conversion. These values were compared with those of methyl isobutyrate (1.65 x 10(-3)) and ethyl lactate (1.03 x 10(-2)), which had been previously determined. A clear dependence was found on the reactivity of the mobile hydrogen atoms alpha with the ester group. All of the macromolecules carried a single ester function. Therefore, the re-initiation step by the CTA-derived radicals overwhelmingly prevailed over initiation by the primary radicals.

Vapor Pressures of Morpholine, Diethyl Methylmalonate, and Five Glycol Ethers at Temperatures up to 473.15 K

Vapor pressures were measured for seven polar organic compounds including morpholine, diethyl methylmalonate, diethylene glycol diethyl ether, diethylene glycol hexyl ether, diethylene glycol dibutyl ether, ethylene glycol monobutyl ether acetate, and diethylene glycol monoethyl ether acetate at temperatures ranging from 308.15 K to 473.15 K. The measured vapor pressures of morpholine, 2-methoxyphenol, and tert-butyl alcohol agree reasonably well with literature values. The Antoine equation correlates the vapor pressure data to AADs of 0.28 % to 0.50 % for the investigated substances.

Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridinones

A rapid synthetic route towards new tricyclic pyridinones, from 6-halogeno-3-nitroimidazo[1,2-a]pyridines bearing the diethyl methylenemalonate group at the 2-position or directly from 6-halogeno-3-nitroimidazo[1,2-a]pyridines bearing the diethyl methylmalonate group at the 2-position, is described.

Bulky Monodentate Phosphoramidites in Palladium‐Catalyzed Allylic Alkylation Reactions: Aspects of Regioselectivity and Enantioselectivity

A series of bulky monodentate phosphoramidite ligands, based on biphenol, BINOL and TADDOL backbones, have been employed in the Pd-catalysed allylic alkylation reaction. Reaction of disodium diethyl 2-methyl malonate with monosubstituted allylic substrates in the presence of palladium complexes of the phosphoramidite ligands proceeds smoothly at room temperature. The regioselectivities observed depend strongly on the leaving group and the geometry of the allylic starting compounds. Mono-coordination occurs when these ligands are ligated in [Pd(allyl)(X)] complexes (allyl=C3H5, 1-CH3C3H4, 1-C6H5C3H4, 1,3-(C6H5)2C3H3; X=Cl, OAc). The solid-state structure determined by X-ray diffraction of [Pd(C3H5)(1)(Cl)] reveals a non-symmetric coordination of the allyl moiety, caused by the stronger trans influence of the phosphoramidite ligand relative to X-. In all of these complexes, the syn,trans isomer is the major species present in solution. Because of fast isomerisation and high reactivity of the syn,cis complex, the major product formed upon alkylation is the linear product, especially for monosubstituted phenylallyl substrates in the presence of halide counterions. In the case of biphenol- and BINOL-based phosphoramidites, however, a strong memory effect is observed when 1-phenyl-2-propenyl acetate is employed as the substrate. In this case, nucleophilic attack competes effectively with the isomerisation of the transient cinnamylpalladium complexes. The asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate afforded the chiral product in up to 93 % ee. Substrates with smaller substituents gave lower enantioselectivities. The observed stereoselectivity is explained in terms of a preferential rotation mechanism, in which the product is formed by attack on one of the isomers of the intermediate [Pd[1,3-(C6H5)2C3H3](L)(OAc)] complex.

Novel Nucleophilic C—C Bond‐Forming tele‐Reaction of Imidazole Ring.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Rapid Syntheses of Nitroheterocycles that Bear a Diethyl Methylenemalonate Group β to a Nitro Group

Rapid syntheses of nitroheterocycles that bear a diethyl methylenemalonate group ?β to a nitro group starting from easily available nitroheterocyclic sulfones and involving, a one-pot substitution-elimination with either diethyl bromomalonate or an original direct olefination with diethyl ketomalonate, gave moderate yields in nitroimidazole series. An SRN1 reaction followed by a base-mediated nitrous acid elimination gave fairly good yields in nitrothiazole series. Because of the accessibility of the reagents, these syntheses are interesting alternatives to Knoevenagel reaction.