54459-73-3

In each of the five title compounds, namely 5-benzylidene-1,3- dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, C13H12N 2O3, (I), 5-(3-methoxybenzylidene)-l,3-dimethylpyrimidine- 2,4,6(l/f,3H,5H)-trione, C14H14N2O4, (II), 5-(4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, C14H14N2O4, (III), 5-[4-(dimethylamino)benzylidene]-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, C15H17N3O3, (IV), and 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H, 5H)-trione, C21H28N2O4, (V), which crystallizes with Z′ = 2 in P1, there is a very wide C-C-C angle at the methine C atom linking the two rings, ranging from 137.1 (2)° in (I) to 139.14 (14)° in (III). There is evidence for intramolecular charge separation in (IV) and, to a lesser degree, in (III). The molecules of (I)-(III) are linked by pairs of C-H...O hydrogen bonds into chains of edge-fused rings, with alternating R22(14) and R2 2(16) rings in (I), alternating R22(14) and R44(20) rings in (II), with two types of R 22(16) rings alternating in (III). The molecules in (IV) are linked by a single C-H...O hydrogen bond into simple C(8) chains, but there are no direction-specific intermolecular interactions in (V).

A novel, environmentally friendly synthesis of 5,9-dihydro-pyrimido[5,4-e][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-diones has been developed by using a one-pot condensation of 1,3-dimethylbarbituric acid, 3-amino-1H-1,2,4-triazoles, and aromatic aldehydes. The reactions were established based on green chemistry principles under catalyst- and solvent-free conditions.

Some novel 5-aminoalkylbarbituric acids and corresponding chromene derivatives were synthesized via a one-pot, three-component Mannich reaction starting from 1,3-dimethylbarbituric acid, arylaldehydes, and amines.

A catalytic, practical, efficient procedure for the synthesis of 5-benzylidene-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione and pyrano[2,3-d] pyrimidine diones at room temperature was developed using L-Proline nitrate ionic liquid under ultrasonic irradiation. The L-Proline nitrate is homogeneous and green catalyst easy to prepare by mixing L-Proline and nitric acid possess excellent catalytic activity under standard ultrasonic bath at room temperature for the synthesis of pyrimidine core. This adequate procedure offers some advantages like the use of green solvent H2O, environmentally green benign procedure, excellent yields, simple procedure, short reaction times, no need for column chromatographic separation and reusability of catalyst for five subsequent reaction.

"Hot loop" protein segments have variable structure and conformation and contribute crucially to protein-protein interactions. We describe a new hot loop mimicking modality, termed PepNats, in which natural product (NP)-inspired structures are incorporated as conformation-determining and-restricting structural elements into macrocyclic hot loop-derived peptides. Macrocyclic PepNats representing hot loops of inducible nitric oxide synthase (iNOS) and human agouti-related protein (AGRP) were synthesized on solid support employing macrocyclization by imine formation and subsequent stereoselective 1,3-dipolar cycloaddition as key steps. PepNats derived from the iNOS DINNN hot loop and the AGRP RFF hot spot sequence yielded novel and potent ligands of the SPRY domain-containing SOCS box protein 2 (SPSB2) that binds to iNOS, and selective ligands for AGRP-binding melanocortin (MC) receptors. NP-inspired fragment absolute configuration determines the conformation of the peptide part responsible for binding. These results demonstrate that combination of NP-inspired scaffolds with peptidic epitopes enables identification of novel hot loop mimics with conformationally constrained and biologically relevant structure.

Johnson-Corey-Chaykovsky fluorocyclopropanation of double activated alkenes utilizing S-monofluoromethyl-S-phenyl-2,3,4,5-tetramethylphenylsulfonium tetrafluoroborate is an efficient approach to obtain a range of monofluorocyclopropane derivatives. So far, fluoromethylsulfonium salts have displayed the broadest scope for direct fluoromethylene transfer. In contrast to more commonly used fluorohalomethanes or freon derivatives, diarylfluoromethylsulfonium salts are bench stable, easy-to use reagents useful for the direct transfer of a fluoromethylene group to alkenes giving access to the challenging products-fluorocyclopropane derivatives. Interplay between the reactivity of the starting materials and stability of the fluorocyclopropanes formed determines the outcome of the process.

Bioactive compounds featuring an unusual core of spiro[5.5]undecenes and calliviminones were synthesized in very good yield with good regio- and diastereoselectivities through a one-pot Knoevenagel and [4 + 2] cycloaddition from the readily available aldehydes, cyclic-1,3-diones, dienes, and a catalytic amount of (s)-proline.

A palladium/XantPhos-catalyzed [5 + 2] annulation of VECs with electron-deficient alkenes having an isolated carbon-carbon double bond has been developed to afford spirobarbiturate-tetrahydrooxepines. This study provides an expedient assembly of biologically interesting spirobarbiturate-tetrahydrooxepines. The easy scalability and versatile transformability of the reaction products were also exhibited.

The present disclosure provides a redox initiator system for initiating polymerization comprising an oxidizing agent, a photolabile reducing agent derived from a barbiturate, and a transition metal complex that participates in a redox cycle. On exposure to actinic radiation, such as UV, the photolabile compound photolyzes, releasing the reducing agent and initiating the redox-initiated polymerization.

An efficient and practical direct alkenylation of 2-methylquinolines with aldehydes has been achieved through a novel synergistic organocatalysis. The HOAc- activated 2-methylquiolines undergo a Michael addition to 1,3-dimethylbarbituric acid-activated aldehydes, followed by a retro-Michael addition to release 1,3-dimethylbarbituric acid and the target products. The transformation produced various 2-alkenylquinolines with good to excellent yields and featured mild reaction conditions, atom- and step-economy, good functional group tolerance, and operational simplicity. (Figure presented.).

A highly efficient domino aza-MIRC (Michael Induced Ring Closure) reaction between barbiturate-derived alkenes and N-alkoxy α-haloamides has been achieved in moderate to excellent yields. This reaction proceeds smoothly under mild conditions via a domino aza-Michael addition/intramolecular SN2 sequence, providing a practical tool in the synthesis of bioactive molecules spirobarbiturate-3-pyrrolidinones.

Fast and reversible dynamic covalent C=C/C=N exchange takes place without catalyst in nonpolar solvents between barbiturate-derived Knoevenagel (Kn) compounds and imines. A detailed study of the reaction indicates that it proceeds by an associative organo-metathesis mechanism involving the formation of a four-membered ring azetidine intermediate by addition of the imine C=N group to the C=C bond of the Kn compound. This intermediate could be generated cleanly and stabilized at low temperature by condensation of the o,p-dinitrophenyl Kn derivative with the cyclic imine 1-azacyclohexene. It was characterized by extensive NMR and mass spectrometric studies. The process described represents a genuine dynamic covalent organo-metathesis through a four-membered ring adduct as intermediate. It paves the way for the exploration of a wide set of dynamic systems involving (strongly) polarized C=C bonds and various imines, extending also into covalent dynamic polymers and polymolecular assemblies.

A metal- and catalyst-free reductive alkylation protocol for the one-pot synthesis of 5-monoalkylbarbiturates from barbituric acids and aldehydes using the in situ generated chemoselective reducing agent 2-phenyl-2,3-dihydrobenzo[ d ]thiazole from 2-aminothiophenol and benzaldehyde is described. The notable advantages of the protocol are operational simplicity, mild reaction conditions, high yield, short reaction time, and simple workup and purification process which make it highly attractive.

The invention relates to the field of oxidative synthesis, and in particular, relates to a 5-hydroxy-5-alkyl disubstituted barbituric acid derivative greenly synthesized by amine catalysis of air oxidation and a method thereof. The amine-catalyzed oxidation reaction of a 5-substituted 1,3-dimethylbarbituric acid derivative is studied; reaction catalysts and solvents are screened, hydroxylation ofalpha-C-H of 5-aryl or benzyl substituted barbituric acid compounds is found out to be realized through catalytic reaction under different conditions. The method has the following characteristics: (1)air is used as the source of hydroxyl functional groups, so the requirements of green development are met; (2) easily available and cheap alkali R3N rather than expensive metal catalysts is used; and(3) stoichiometric harmful phosphine compounds are prevented from being used as additives and reductants.

Abstract: A simple method is developed to prepare an efficient and low cost acid–base bifunctional catalyst by using poly 2-(dimethyl amino) ethyl methacrylate as a basic part and hierarchical ZSM-5 as an acidic part of the catalyst. Tandem reaction of deacetalization–Knoevenagel condensation was selected to evaluate the prepared catalyst and the outcomes were excellent. Graphical Abstract: [Figure not available: see fulltext.].

Three cyclic zinc(II) bis-porphyrins (CB) with highly flexible linkers are employed as artificial molecular containers that efficiently encapsulate/coordinate various aromatic aldehydes within their cavities. Interestingly, the arrangements of guests and their reactivity inside the molecular clefts are significantly influenced by the cavity size of the cyclic containers. In the presence of polycyclic aromatic aldehydes, such as 3-formylperylene, as a guest, the cyclic bis-porphyrin host with a smaller cavity (CB1) forms a 1:1 sandwich complex. Upon slightly increasing the spacer length and thereby the cavity size, the cyclic host (CB2) encapsulates two molecules of 3-formylperylene that are also stacked together due to strong π–π interactions between them and CH–π interactions with the porphyrin rings. However, in the cyclic host (CB3) with an even larger cavity, two metal centers of the bis-porphyrin axially coordinate two molecules of 3-formylperylene within its cavity. Different arrangements of guest inside the cyclic bis-porphyrin hosts are investigated by using UV/Vis, ESI-MS, and 1H NMR spectroscopy, along with X-ray structure determination of the host–guest complexes. Moreover, strong binding of guests within the cyclic bis-porphyrin hosts support the robust nature of the host–guest assemblies in solution. Such preferential binding of the bis-porphyrinic cavity towards aromatic aldehydes through encapsulation/coordination has been employed successfully to catalyze the Knoevenagel condensation of a series of polycyclic aldehydes with active methylene compounds (such as Meldrum's acid and 1, 3-dimethylbarbituric acid) under ambient conditions. Interestingly, the yields of the condensed products significantly increase upon increasing spacer lengths of the cyclic bis-porphyrins because more substrates can then be encapsulated within the cavity. Such controllable cavity size of the cyclic containers has profound implications for constructing highly functional and modular enzyme mimics.

A green and efficient method have been developed for the synthesis of quaternary centered and spiro-barbiturate-tetrahydrothiophene hybrids via Knoevenagel condensation,1,4-thia-Michael and intramolecular Aldol reactions using “on water” concept under catalyst-free conditions. Systematic studies were carried out to find the role of the water and total reaction concentration (0.086?M) to promote the reaction in two steps (one-pot). The use of water as a reaction medium, catalyst-free conditions, broad substrate scope, one-pot approach for the creation of quaternary centered and spiro molecules are the advantages of this method.

The study is devoted to one-pot reaction of 1,3-dimethylbarbituric acid with aromatic aldehydes and ammonium acetate using Fe3O4 nanoparticles as efficient and magnetically recyclable catalysts. Aromatic aldehydes substituted with electron-withdrawing groups or none, reacted successfully with 1,3-dimethylbarbituric acid and ammonium acetate to give new pyrimido[5′,4′:5,6]pyrido[2,3-d]pyrimidine derivatives (can be also named as pyrido[2,3-d:6,5-d′]dipyrimidines) in high yields over relatively short reaction time. The Knoevenagel condensation products were isolated using aromatic aldehydes bearing electron-donating substituents. The catalyst could be efficiently used for four times without substantial reduction in its activity. The new products were characterized on the basis of FT-IR, 1H NMR and 13C NMR spectral data.

A multifunctional chiral phosphine-catalyzed enantioselective [3+2] annulation of Morita–Baylis–Hillman carbonates with barbiturate-derived alkenes has been achieved under mild conditions, providing a variety of chiral spirobarbiturate-cyclopentenes in moderate to excellent yields with moderate to excellent diastereo- and enantioselectivities. (Figure presented.).

The present invention relates to methods of inhibiting shikimate pathway, comprising administering to a subject a pharmaceutically acceptable composition comprising a compound having a formula: or pharmaceutically acceptable salts thereof. The present invention also provides a synergistic antibacterial composition containing compound

The Knoevenagel condensation between aromatic aldehydes and malononitrile, barbituric acid or 1,3-dimethylbarbituric acid with ethane-1,2-diammonium hydrogen sulfate (EDAHS) in aqueous micellar media, using sodium dodecyl sulfate is described. EDAHS was found to be a highly active and stable Bronsted acidic ionic liquid catalyst under the reaction conditions. Graphical Abstract: [Figure not available: see fulltext.].

A solvent-free approach for the synthesis of a series of pyrimido[5',4':5,61pyrido[2,3-d]pyrimidinetetraone and 4-arylacridinedione derivatives is described herein. These compounds having biological importance were prepared via a condensation reaction of aryl aldehydes, ammonium acetate and active methylene compounds including 1,3-dimethylbarbituric acid or dimedone under solvent-free conditions, using Zr(HPO4)2.H 2O (α-ZrP) as an efficient catalyst. The reusability of catalyst and easier isolation of the products along with high yields of products are the advantages of this eco-friendly and versatile protocol.

Mechanism of hydride transfer reactions to form olefins is still a conundrum. Here, we propose an electron transfer (ET) followed by hydrogen atom transfer (HT) as the most likely mechanism for hydride transfer reactions from the hydride adducts of olefins (G-XH-) to a carbocation (T+) in acetonitrile. This is confirmed by the analysis of the energetics of each mechanistic step, estimated from ΔHH - (the hydride affinity) and redox potentials of the related species, and activation energetics calculated from rate constants of the hydride transfer from G-XH- to T+.

A series of N,N-dimethyl-arylidene barbiturates 1-22 has been re-synthesized and evaluated against a number of Gram-positive, Gram-negative bacteria and some fungal strains. Most of the compounds were found to be active against a number of Gram-positive, Gram-negative and also displayed anti-fungal activities.

Some novel symmetrical bis(pyrrolo[2,3-d]pyrimidinyl)methanes were synthesized via diheteroarylation of sp3 CH bond of acetophenones with molecular iodine and DMSO. Further, an efficient reaction protocol was developed with which both symmetrical and some novel unsymmetrical bis(pyrrolo[2,3-d]pyrimidinyl)methanes were synthesized. For this purpose, we have exploited the highly reactive and good leaving nature of 1,3-dimethylbarbituric acid.

A series of 69 polar olefins with various typical structures (X) were synthesized and the thermodynamic affinities (defined in terms of the molar enthalpy changes or the standard redox potentials in this work) of the polar olefins obtaining hydride anions, hydrogen atoms, and electrons, the thermodynamic affinities of the radical anions of the polar olefins (X ?-) obtaining protons and hydrogen atoms, and the thermodynamic affinities of the hydrogen adducts of the polar olefins (XH?) obtaining electrons in acetonitrile were determined using titration calorimetry and electrochemical methods. The pure Ci - 'C π-bond heterolytic and homolytic dissociation energies of the polar olefins (X) in acetonitrile and the pure Ci - 'C π-bond homolytic dissociation energies of the radical anions of the polar olefins (X?-) in acetonitrile were estimated. The remote substituent effects on the six thermodynamic affinities of the polar olefins and their related reaction intermediates were examined using the Hammett linear free-energy relationships; the results show that the Hammett linear free-energy relationships all hold in the six chemical and electrochemical processes. The information disclosed in this work could not only supply a gap of the chemical thermodynamics of olefins as one class of very important organic unsaturated compounds but also strongly promote the fast development of the chemistry and applications of olefins.

Unique three-component self-assembly of a cis-blocked 90° Pd(ii) acceptor with a mixture of tri- and tetra-imidazole donors led to the self-sorting of a Pd7 molecular boat with an internal nanocavity, which catalyses the Knoevenagel condensation of a series of aromatic aldehydes with 1,3-dimethylbarbituric acid and Meldrum's acid in aqueous media.

N,N'-dimethylbarbituric acid derivatives 1-24 were evaluated for their xanthine oxidase (XO) inhibitory activity. Majority of these compounds showed a good to moderate in vitro xanthine oxidase inhibitory activity (IC50 = 20.97 ± 0.29 - 327.0 ± 3.50 μM), while eight compounds were found to be completely inactive. A structure-activity relationship has been discussed, identifying structural features, responsible for varying degree of activity.

The low-valent iron complex Bu4N[Fe(CO)3(NO)] (TBAFe) catalyzes the allylic C-C-bond activation of electron-poor vinyl cyclopropanes to generate synthetically useful a1,a3,d5-synthons which are prone to undergo multiple consecutive reactions. The versatility of this approach is demonstrated by a traceless allylic substitution and a formal [3 + 2] cycloaddition to give either functionalized acyclic products or densely substituted cyclopentanes and pyrrolidines in high yields and regioselectivities.

Comparison of the 1H and 13 C NMR spectra of a series of substituted 5-benzylidene-N,N′-dimethylbarbituric acids (1) revealed chemical-shift variations of different centers that correlated with the theoretical electrophilicities or with the substituent electrophilic constant σω, in an example of the usefulness of these DFT-based indices. Copyright

A microwave-assisted, one-pot three-component aza-Diels-Alder reaction strategy has been developed for the synthesis of some complex spiroquinoline derivatives from 1-aminonaphthalene, aromatic aldehyde, and 5-benzylidene-1,3- dimethyl pyrimidine-2,4,6-trione under catalyst- and solvent-free conditions.

Reaction of barbituric acid (BA), 1,3-dimethyl barbituric acid (DMBA) and 2-thiobarbituric acid (TBA) with cyanogen bromide and aldehydes in the presence of L-(+)-tartaric acid afforded a new route for the synthesis of stable heterocyclic 5-aryl-1H,1′H-spiro[furo[2,3-d]pyrimidine-6,5′- pyrimidine]2,2′,4,4′,6′(3H,3′H,5H)- pentaones which is a dimeric form of barbiturate (uracil and thiouracil derivative). In the reaction of 1,3-diethyl thiobarbituric acid (DETBA) the Knoevenagel condensation and then Michael adducts were obtained under the same condition. Structure elucidation is carried out by 1H NMR, 13C NMR, FT-IR and Mass analyses. Mechanism of the formation is discussed.

Twenty-four derivatives of N,N-dimethylbarbituric acid 1-24 were screened for their DPPH radical scavenging activity. These compounds showed an excellent antioxidant activity. A structure-activity relationship has been discussed, while all the synthetic compounds were characterized by spectroscopic techniques and elemental analysis.

The one-pot three-component reactions of 1,3-dimethylbarbituric acid, aromatic aldehydes and alkyl or aryl isocyanides proceed smoothly at room temperature to give the corresponding 5-aryl-6-alkyl or arylamino-1,3- dimethylfuro [2,3-d] pyrimidine-2, 4 (1H,3H)-dione derivatives in good to excellent yields within 30 minutes in DMF. This three-component reaction represents a facile and efficient route to the described biologically interesting molecules.

The three-component reactions of in-situ-formed N-benzylbenzimidazolium salts, aromatic aldehydes, and active methylene compounds in the presence of triethylamine showed very interesting molecular diversity. The reactions with Meldrum's acid or barbiturate in acetonitrile gave a series of the novel zwitterionic salts in high yields. Under similar reaction conditions, the reactions with malononitrile or ethyl cyanoacetate produced functionalized pyrrolo[1,2-a]benzimidazoles in good yields with an unprecedented regioselectivity.

An efficient synthetic procedure for the preparation of the unusual charge-separated pyridinium-Meldrum acid and N,N-dimethylbarbiturate acid zwitterionic salts was developed though a unique one-pot fourcomponent reaction involving pyridine, aromatic aldehyde, Meldrum acid or N,N-dimethylbarbituric acid, and p-nitrobenzyl bromide in acetonitrile. By varying combinations of four components involving nitrogencontaining heterocycles, we conveniently established reactiveα-halomethylene compounds, aldehydes and β-dicarbonyl compounds a library of zwitterionic salts.

On-water Knoevenagel condensations of 2-thiobarbituric acid and N,N-dimethylbarbituric acid with aromatic and heteroaromatic aldehydes were carried out without a catalyst and at room temperature. Condensations in aqueous suspensions occurred rapidly, giving excellent yields. Solvent-free hetero-Diels-Alder reactions of 5-arylidene derivatives of barbituric acids with ethyl vinyl ether were investigated at room temperature and pyrano[2,3-d]pyrimidines of potential pharmacological activity were obtained in excellent yields. Three-component one-pot syntheses of annulated uracils were performed in aqueous suspensions. Reactions of barbituric acids, aldehydes, and ethyl vinyl ether were carried out at ambient temperature, whereas the one-pot synthesis with barbituric acids, aldehydes, and styrene or N-vinyl-2- oxazolidinone required the heating of aqueous suspensions at 60°C. On-water cycloadditions were characterized by high diastereoselectivity in contrast to reactions carried out in homogeneous organic media (dichloromethane, toluene). They allowed the cis adducts to be obtained preferentially or exclusively. The presented green methods avoid the use of catalysts, the heating of reaction mixtures for long times at high temperatures, and the use of organic solvents, and make the synthesis of a variety of pyrano[2,3-d]pyrimidines chemically efficient. The results reveal water as the medium of choice for the examined cycloadditions. Georg Thieme Verlag Stuttgart - New York.

5-Isopropenyl-2,3-dihydrothiophene 1,1-dioxide reacted with 5-methylidenepyrimidine-2,4,6-triones and 5-methylidene-2-thioxopyrimidine-4,6- diones in the presence of chiral amines or amino acids with high regio- and stereoselectivity to give optically active derivatives of barbituric and thiobarbituric acids spirofused at the 5-position to 1-benzothiophene 1,1-dioxide fragment. The reaction of 5-isopropenyl-2,3-dihydrothiophene 1,1-dioxide with 5-(2-methoxybenzylidene)-2-thioxopyrimidine-4,6-dione (generated in situ from 2-methoxybenzaldehyde and thiobarbituric acid) in the presence of (-)-ephedrine or L-4-(tert-butyldimethylsiloxy) proline gave the corresponding 2-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′, 6′-dione 1,1-dioxide with an enantiomeric excess of 80%.

The syntheses of a new class of barbiturate-based inhibitors for human and Escherichia Coli methionine aminopeptidase-1 (MetAP-1) are described. Some of the synthesized inhibitors show selective inhibition of the human enzyme with high potency.

A novel and efficient synthesis of 2-aroyl-1,4-diaryl-7,9-dimethyl-7,9- diazaspiro[4.5]deca-1,3-diene-6,8,10-triones is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of triphenylphosphine to diaroylacetylenes, was trapped by a Knoevenagel condensation product prepared in situ by reaction of AyV-dimethylbarbituric acid and aromatic aldehydes, to afford the title compounds in excellent yields under mild reaction conditions.

5-Arylidene-N,N-dimethylbarbituric acids undergo smooth hetero-Diels-Alder reactions with enol ethers to afford cis and trans diastereoisomers of 7-alkoxy-5-aryl-2H-pyrano[2,3-d]pyrimidine-2,4-diones in excellent yields (84-95%). Cycloadducts with cis-configuration were the major products. Three-component one-pot reactions of N,N-dimethylbarbituric acid, aromatic and heteroaromatic aldehydes, and enol ethers in the presence of piperidine gave uracils also in very good yields (87-95%). The structure of the cycloadducts is discussed in terms of configuration and preferred conformation.

Synthesis of some novel 3-alkylated indoles via an uncatalyzed Michael addition of indoles using three components in one-pot solvent-free conditions is reported. The mechanism was established by performing the reaction in two steps. The reaction was also studied in different solvents and an important solvent effect was noticed.

A novel and green approach for the two-carbon homologation of aldehydes using amino acid catalysis has been developed and further extended to the generation of pharmaceutically active cyano-esters via four-component reactions in one-pot.

Knoevenagel condensation of various aromatic and heteroaromatic aldehydes with active methylene compounds like malononitrile, ethyl cyanoacetamide, ethyl cyanoacetate, barbituric acids, Meldrum's acid, dimedone and pyrazolone proceeds smoothly with stirring in an aqueous medium. The reactions occur at room temperature giving excellent yields of the products. The work-up procedure is very simple and the products do not require further purification.

Through systematic exploration of reaction conditions, very efficient preparative procedures for obtaining large quantities of substituted 5-alkyl and 5-benzylbarbituric acids were developed. The procedure involves a two step preparation in which the second step is zinc dust/acid reduction. For preparation of 5-alkylbarbiturates, the first step is the preparation of either 5-acyl or 5-alkylidenebarbiturate. If 5-benzylbarbiturate is the target product, then the first step includes the preparation of 5-benzylidene. Regardless of the nature of the first step, all reactions presented synthetic yields around 90% and isolation and purification involves only crystallization.

Effective synthetic procedures for the preparation of mono- and di-C-alkylated barbituric acid derivatives through palladium and platinum catalytic hydrogenation of solutions of barbituric acids (unsubstituted, N-mono, and N,N′-disubstituted barbituric acids) and carbonyl compounds (aliphatic and aromatic aldehydes and ketones).

Synthetic utility of the novel difluoro ketene aminal 1 was extended to the preparation of a number of potentially biologically-interesting difluoro barbituric acid derivatives via initial hetero-Diels-Alder reactions of 1 with p-substituted-5-benzylidene-1,3-dimethylbarbituric acids 3. These cycloadducts 4 upon hydrolysis, provided the formal Michael addition product amides 5 which were readily converted to the respective carboxylic acids 6. The acids were dehydratively cyclized to form novel bicyclic lactones 8.

Anhydrous zinc chloride has been found to be an efficient catalyst in carbonyl-methylene condensation reactions.The synthesis of arylidene acetonitriles (6a-g, 7a-g) and arylidene heterocycles (8a-e, 9a-e) have been accomplished in high yields and good purity.

Barbiturylbenzylidenes, prepared by Perkin condensation of aromatic aldehydes with 1,3-dimethylbarbituric acid, react with phenylisonitrile to yield four 5-aryl-6-phenylamino-1,3-dimethylfuropyrimidine-2,4(1H,3H)-diones.

Various 5-arylidene 1,3-dimethylbarbituric acid derivatives and closely related compounds were synthesized as models of redox coenzymes and used for oxidation of alcohols.Under mild neutral conditions, 5-arylidene 1,3-dimethylbarbituric acid derivatives, especially those having an electron-withdrawing group on the aromatic ring, effectively oxidized allylic and benzylic alcohols to the corresponding carbonyl compounds.The relationship between the oxidizing ability and the structure of the oxidant (coenzyme model) was investigated and it was found that the electron density on the carbon-carbon double bond is a critical factor for the oxidation.In the case of the deuterium-labeled compound, the observed value of normal and primary isotope effect was 3.3 and so it was concluded that mechanism of this oxidation mainly involves the hydride transfer from the alcohol.An electrochemical investigation was also carried out and the redox potentials of the coenzyme models, 5-arylidene 1,3-dimethylbarbituric acid derivatives and related compounds, were measured.Keywords - 5-arylidene 1,3-dimethylbarbituric acid; coenzyme model; oxidation; allylic alcohol; benzylic alcohol; oxidation mechanism; hydride transfer; primary isotope effect; cyclic voltammetry; redox potential