Trisubstituted Ureas Research Articles

New insight into the use of latent catalysts for the synthesis of urea formaldehyde adhesives and the mechanical properties of medium density fiberboards bonded with them

Recently, there has been a rapid growth in research and innovation in the synthesis of UF resins in the wood-based composites area. Much effort has gone into increasing their mechanical performance to extend the capabilities and application of this group of materials. This paper, for the first time, defines the research on the use of ammonium salts not as hardeners but in the synthesis of UF resins. The objective of this study was to investigated the effects of various types of catalysts (ammonium sulfate, ammonium chloride, sulfuric acid and hydrochloric acid) during UF resins synthesis on formaldehyde emission and characteristics of urea–formaldehyde (UF) adhesives for the manufacture of medium density fiberboard. These were investigated by 13C Nuclear Magnetic Resonance (13C NMR) and differential scanning calorimetry (DSC), and as a result some of the physical and mechanical properties of medium density fiberboard (MDF) panels bonded with different UF resins were evaluated. The resins structure examined by 13C NMR spectroscopy showed that a resin catalyzed by (NH4)2SO4 had a higher proportion of hydroxymethyl groups (mostly HNCH2OH) resulting in a higher level of formaldehyde emission. A resin catalyzed by NH4Cl gave the highest proportion of methylene groups. A resin catalyzed by H2SO4 yielded the highest proportion of methylene groups in di- or tri-substituted ureas but the lowest proportion of mono-substituted urea. It was of interest that (NH4)2SO4 catalyzed UF adhesive yielded the best overall mechanical properties for the medium density fiber board (MDF) bonded with it. Conversely, it also presented the shortest shelf life and gelled in about 15 days, which could be related to its high reactivity and shortest gel time. Medium Density Fiberboard (MDF) panels bonded with UF adhesives without any ammonium salt (thus with either H2SO4 or HCl) had lower IB strength, MOR and MOE. The HCl catalyst was considered to be chemically least active, yielding the lowest cohesive energy, and resulted in panels presenting a poor performance as shown by their lowest IB (internal bond) strength, modulus of elasticity (MOE), and modulus of rupture (MOR) and highest thickness swelling, with the exception of the free formaldehyde content.

Hydroxoiridium‐Catalyzed Hydroalkylation of Terminal Alkenes with Ureas by C(sp3)−H Bond Activation

AbstractDirect alkylation of a methyl group, on di‐ and trisubstituted ureas, with terminal alkenes by C(sp3)−H bond activation proceeded in the presence of a hydroxoiridium/bisphosphine catalyst to give high yields of the corresponding addition products. The hydroxoiridium/bisphosphine complex generates an amidoiridium intermediate by reaction with ureas having an N−H bond.

Hydroxoiridium-Catalyzed Hydroalkylation of Terminal Alkenes with Ureas by C(sp3 )-H Bond Activation.

Direct alkylation of a methyl group, on di- and trisubstituted ureas, with terminal alkenes by C(sp3 )-H bond activation proceeded in the presence of a hydroxoiridium/bisphosphine catalyst to give high yields of the corresponding addition products. The hydroxoiridium/bisphosphine complex generates an amidoiridium intermediate by reaction with ureas having an N-H bond.

ChemInform Abstract: One‐Pot Synthesis of Trisubstituted Ureas from α‐Chloroaldoxime O‐Methanesulfonates and Secondary Amines.

AbstractThe reaction proceeds via intermediary isocyanates generated by Tiemann‐type rearrangement of α‐chloroaldoxime mesylates in the presence of water and a base.

One-pot synthesis of trisubstituted ureas from α-chloroaldoxime O-methanesulfonates and secondary amines

Trisubstituted ureas can be synthesized in a one-pot fashion from bench-stable α-chloroaldoxime O-methanesulfonates and secondary amines under mild reaction conditions.

ChemInform Abstract: One‐Pot Synthesis of Ureas from Boc‐Protected Amines.

AbstractNonsymmetrical and symmetrical disubstituted and trisubstituted ureas are synthesized by using 2‐chloropyridine and TfO2 for the in situ generation of an isocyanate.

Synthesis and folding propensity of aliphatic oligoureas containing repeats of proline-type units.

The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity.

One-pot synthesis of ureas from Boc-protected amines.

A practical one-pot synthesis of ureas is described. Boc-protected amines can be transformed into nonsymmetrical and symmetrical disubstituted and trisubstituted ureas utilizing 2-chloropyridine and trifluoromethanesulfonyl anhydride for the in situ generation of an isocyanate, which reacts with an amine. A variety of amines can be employed successfully, leading to high yields of isolated ureas.

Discovery of 1-oxa-4,9-diazaspiro[5.5]undecane-based trisubstituted urea derivatives as highly potent soluble epoxide hydrolase inhibitors and orally active drug candidates for treating of chronic kidney diseases

We identified 1-oxa-4,9-diazaspiro[5.5]undecane-based trisubstituted ureas as highly potent soluble epoxide hydrolase (sEH) inhibitors and orally active agents for treating chronic kidney diseases. Compound 19 exhibited excellent sEH inhibitory activity and bioavailability. When administered orally at 30mg/kg, 19 lowered serum creatinine in a rat model of anti-glomerular basement membrane glomerulonephritis but 2,8-diazaspiro[4.5]decane-based trisubstituted ureas did not. These results suggest that 19 is an orally active drug candidate for treating chronic kidney diseases.

ChemInform Abstract: Synthesis of Trisubstituted Ureas by a Multistep Sequence Utilizing Recyclable Magnetic Reagents and Scavengers.

Unprecedented magnetic borohydride exchange (mBER), magnetic Wang aldehyde (mWang) and magnetic amine resins were prepared from highly magnetic polymer-coated cobalt or iron nanoparticles. Microwave irradiation was used to obtain excellent degrees of functionalization (>95 %) and loadings (up to 3.0 mmol g−1) in short reaction times of 15 min or less. A small library of ureas and thioureas was synthesized by the exclusive application of these magnetic resins. As a first step, a reductive amination of aromatic and aliphatic aldehydes was carried out with mBER. The excess of primary amine needed to complete the reaction was subsequently scavenged selectively by mWang. Simple magnetic decantation from the resins resulted in secondary amines in good to excellent yields and purities. The used magnetic resins were efficiently regenerated and reused for the next run. In a second step, the secondary amines were converted to trisubstituted (thio)ureas in excellent yields and purities by stirring with an excess of iso(thio)cyanate, which was scavenged by addition of the magnetic amine resin after completion of the reaction. The whole reaction sequence is carried out without any purification apart from magnetic decantation; moreover, conventional magnetic stirring can be used as opposed to the vortexing required for polystyrene resins.

ChemInform Abstract: AlMe3‐Mediated Regio‐ and Chemoselective Reactions of Indole with Carbamoyl Electrophiles.

Herein, we report the regio- and chemoselective reactions of indole with carbamoyl electrophiles in presence of AlMe3. Indole-3-carboxamide was prepared in one-step from a reaction of indole with tertiary carbamoylimidazole in the presence AlMe3. Under conditions for the formation of an aluminium ate complex, the reaction was diverted to the indole nitrogen. Secondary carbamoyl electrophiles in the presence of AlMe3 regiospecifically yielded trisubstituted ureas. The regiospecificity and chemoselectivity of the indole nitrogen towards ester and tertiary carbamoylimidazole functionalities were also studied.

Synthesis of Trisubstituted Ureas by a Multistep Sequence Utilizing Recyclable Magnetic Reagents and Scavengers

Unprecedented magnetic borohydride exchange (mBER), magnetic Wang aldehyde (mWang) and magnetic amine resins were prepared from highly magnetic polymer-coated cobalt or iron nanoparticles. Microwave irradiation was used to obtain excellent degrees of functionalization (>95 %) and loadings (up to 3.0 mmol g(-1)) in short reaction times of 15 min or less. A small library of ureas and thioureas was synthesized by the exclusive application of these magnetic resins. As a first step, a reductive amination of aromatic and aliphatic aldehydes was carried out with mBER. The excess of primary amine needed to complete the reaction was subsequently scavenged selectively by mWang. Simple magnetic decantation from the resins resulted in secondary amines in good to excellent yields and purities. The used magnetic resins were efficiently regenerated and reused for the next run. In a second step, the secondary amines were converted to trisubstituted (thio)ureas in excellent yields and purities by stirring with an excess of iso(thio)cyanate, which was scavenged by addition of the magnetic amine resin after completion of the reaction. The whole reaction sequence is carried out without any purification apart from magnetic decantation; moreover, conventional magnetic stirring can be used as opposed to the vortexing required for polystyrene resins.

Assembly of N,N-disubstituted-N′-arylureas via a copper-catalyzed one-pot three-component reaction of aryl bromides, potassium cyanate, and secondary amines

A three-component reaction of aryl bromides, potassium cyanate, and secondary amines takes place at 110 °C in MeCN under the catalysis of Cu2O and 2-(2,6-dimethylphenylamino)-2-oxoacetic acid potassium salt, giving N,N-disubstituted-N′-arylureas in good to excellent yields. A number of functionalized aryl bromides and secondary amines were compatible with these conditions, and thereby providing a facile method for diverse synthesis of trisubstituted ureas.

AlMe3‐Mediated Regio‐ and Chemoselective Reactions of Indole with Carbamoyl Electrophiles

AbstractHerein, we report the regio‐ and chemoselective reactions of indole with carbamoyl electrophiles in presence of AlMe3. Indole‐3‐carboxamide was prepared in one‐step from a reaction of indole with tertiary carbamoylimidazole in the presence AlMe3. Under conditions for the formation of an aluminium ate complex, the reaction was diverted to the indole nitrogen. Secondary carbamoyl electrophiles in the presence of AlMe3 regiospecifically yielded trisubstituted ureas. The regiospecificity and chemoselectivity of the indole nitrogen towards ester and tertiary carbamoylimidazole functionalities were also studied.

ChemInform Abstract: Substituted Ureas Based on 2,6‐Dimethyl‐3,5‐pyridinedicarboxylic Acid Azides.

AbstractAzides (I) and (VII) are converted into the corresponding isocyanate intermediates by Curtius rearrangement which further react with ammonia, primary, secondary amines to give mono‐, di‐, and trisubstituted ureas.

New potent calcimimetics: II. Discovery of benzothiazole trisubstituted ureas

Following the identification of trisubstituted ureas as a promising new chemical series of allosteric modulators of the calcium sensing receptor (CaSR), we further explored the SAR around the urea substitution, leading to the discovery of benzothiazole urea compound 13. This compound is a potent calcimimetic with an EC50=20nM (luciferase assay). Evaluated in an in vivo model of chronic renal failure (short term and long term in 5/6 nephrectomized rats), benzothiazole urea 13 significantly decreased PTH levels after oral administration while keeping calcemia within the normal range.

New potent calcimimetics: I. Discovery of a series of novel trisubstituted ureas

Starting from Fendiline and R-568, we identified a novel series of urea compounds as positive allosteric modulators of the calcium sensing receptor (CaSR), as part of a program to identify novel therapeutics for secondary hyperparathyroidism. Initially identified disubstituted ureas were converted to trisubstituted urea lead 20e, which was further modified to increase in vivo potency. Replacing a carbomethoxy substituent by various bioisosteres led to compound 46 which exhibited potent in vitro and in vivo activity after oral administration.

Synthesis, spectroscopic, structural and conformational study of some tri-substituted ureas derived from N-methylpiperazine containing phenyl and N-heterocyclic substituents

A series of tri-substituted ureas containing an N-methylpiperazine moiety as well as phenyl and N-heterocyclic substituents were synthesized and studied by 1H, 13C NMR and IR spectroscopies. From 1H and 13C NMR data, in CDCl3 solution at room temperature, a fast inter-conversion of the piperazine ring with the N-CH3 group in equatorial position can be proposed. Amino–imino tautomerism is observed for both thiazole and benzothiazole derivatives. Moreover, with the exception of the imino form of the thiazole derivative, the aryl substituted N-carbamoyl group rotates freely. IR data show that the compounds adopt a planar trans conformation of the CONH moiety.

Substituted ureas based on 2,6-dimethyl-3,5-pyridinedicarboxylic acid azides

Under Curtius rearrangement conditions, 2,6-dimethyl-3,5-pyridinedicarboxylic acid azides form the corresponding isocyanates which react in situ with ammonia, primary and secondary amines to form mono-, di-, and trisubstituted ureas. The reaction of the 5-ethoxycarbonyl-2,6-dimethylnicotinic acid azide with imidazole under these conditions gave symmetrical N,N'-bis[5-(ethoxycarbonyl)-2,6-di-methylpyridin-3-yl]ureas.

ChemInform Abstract: Iron(III) Catalyzed Synthesis of Unsymmetrical Di‐ and Trisubstituted Ureas — A Variation of Classical Ritter Reaction.

AbstractA mild synthesis of the title compounds is presented from cheap and readily available alcohols and with an inexpensive, nontoxic catalyst.