Stoichiometric Reactions of CO2 and Indium‐Silylamides and Catalytic Synthesis of Ureas

The indium compounds In(N(SiMe₃)₂)₂Cl⋅THF ( 2 ) and In(N(SiMe₃)₂)Cl₂⋅(THF)_n ( 3 ) were shown to react with CO₂ to give [(Me₃Si)₂N)InX(μ‐OSiMe₃)]₂ (X=N(SiMe₃)₂ 4 , Cl 5 ). 0.05–2.0 mol % of the species 3 acts as a pre‐catalyst for the conversion of aryl and alkyl silylamines under CO₂ (2–3 atm) to give the corresponding ureas in 70–99 % yields. A proposed mechanism is supported by experimental and computational data.     

Synthesis,Bioactivities and Structure Activity Relationship of N‐4‐Methyl‐1,2,3‐thiadiazole‐5‐carbonyl‐N′‐phenyl Ureas

Twenty nine novel N‐4‐methyl‐1,2,3‐thiadiazole‐5‐carbonyl‐N′‐phenyl ureas were designed and synthesized, and their structures were confirmed by proton nuclear magnetic resonance (¹H NMR), infra red spectroscopy (IR) and high‐resolution mass spectroscopy (HRMS). Compounds V‐9 , V‐11 , V‐12 , V‐15 , V‐19 , V‐21 , V‐22 and V‐24 exhibit excellent activity against Culex pipiens pallens. Compounds V‐12 and V‐22 present good insecticidal activity against Plutella xylostella L. Their median lethal concentrations (LC₅₀) are 164.15 and 89.69 mg·L^?1, respectively. Compound V‐11 also has potential wide spectrum of fungicide activity. Its median effective concentrations (EC₅₀) detected from 3.82 µg·mL^?1 against Physalospora piricola to 31.60 µg·mL^?1 against Cercospora arachidicola. Compounds V‐15 and V‐24 show outstanding induction activities as same as positive controls TDL and ningnanmycin, furthermore V‐24 has the highest induction activity of 41.85%±4.43%. To elucidate the structure activity relationship in these compounds, a 3D‐QSAR model has been built. The established model showed a reliable predicting ability with q² values of 0.643 and r² values of 0.982.     

‘All‐supramolecular’ Nanocapsules from Low‐Molecular Weight Ureas Through Interfacial Addition Reaction in Miniemulsion

This contribution presents a new strategy for preparing nanocapsules with a shell made of a supramolecular polymer which repeating units are held together by reversible interactions rather than covalent bonds. These nanocapsules were prepared in classical miniemulsion through interfacial addition reaction of a diisocyanate (IPDI) and a monoamine (iBA), forming low‐molecular weight bis‐ureas moieties which are strong self‐complementary interacting molecules through hydrogen‐bonding. The nanocapsules present a diameter around 100 nm, and MALDI‐TOF MS and ¹H NMR analyses confirm the expected molecular characteristics for the shell. This strategy opens the scope of a new type of nanomaterials exhibiting stimuli‐responsiveness due to the reversible interaction linking the repeating units.

     

Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2

A robust, click‐chemistry‐inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable for all carbon isotopes (¹¹C, ¹³C, ¹⁴C), is based on the direct functionalization of carbon dioxide: the universal building block for carbon radiolabeling. The strategy is operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity as compared to previously reported systems. With this procedure, a variety of pharmaceuticals and an unprotected peptide were labeled with high radiochemical efficiency.     

Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2‐Hydroxypyrimidine/Pyrimidin‐2(1H)‐one Tautomers

A facile access to optically active cyclic ureas was developed through palladium‐catalyzed asymmetric hydrogenation of pyrimidines containing tautomeric hydroxy group with up to 99 % ee. Mechanistic studies indicated that reaction pathway proceed through hydrogenation of C=N of the oxo tautomer pyrimidin‐2(1H)‐one, acid‐catalyzed isomerization of enamine–imine, and hydrogenation of imine pathway. In addition, the chiral cyclic ureas are readily converted into useful chiral 1,3‐diamine and thiourea derivatives without loss of optical purity.     

Reactivity of Hydroxy and Amino Derivatives of 2‐Phenyl‐1H‐imidazoline and 2‐Phenyl‐1H‐imidazole toward Isocyanates: Synthesis of Appropriate Carbamates and Ureas

Reactivity of 2‐(4‐hydroxyphenyl)‐1H‐imidazoline and 2‐(4‐hydroxyphenyl)‐1H‐imidazole toward substituted phenyl isocyanates was studied. When mentioned imidazoline was treated with 2.5 equiv of substituted phenyl isocyanate, three N,O‐dicarboxamides were prepared (substituents are H, 4‐NO₂, and 4‐CH₃). Subsequently, N,O‐diacetylated 2‐(4‐hydroxyphenyl)‐1H‐imidazoline was prepared and selective deprotection method was developed for preparation of 1‐acetyl‐2‐(4‐hydroxyphenyl)‐1H‐imidazoline using diethylamine in acetone. Six carbamates derived from this imidazoline were then prepared using 1.1 equiv of substituted phenyl isocyanates (substituents are H, 4‐CH₃, 4‐OCH₃, 4‐NO₂, 4‐CN, and 3‐CF₃). Finally, two carbamates were prepared from 2‐(4‐hydroxyphenyl)‐1H‐imidazole (substituents are 4‐NO₂ and 4‐CN). No reactivity to imidazole ring was observed in this case. Eight derivatives were subjected to antimycobacterial screening. Concurrently, reactivity of 2‐(2‐aminophenyl)‐ and 2‐(2‐hydroxyphenyl)‐1H‐imidazole toward aliphatic and aromatic isocyanates was studied. Eight ureas were prepared using equivalent mixture of 2‐(2‐aminophenyl)‐1H‐imidazole and isocyanate (Et, Pr, isoPr, terc‐Bu, Cy, Ph, 4‐CH₃C₆H₄, 4‐CNC₆H₄). Similar attempts to obtain related carbamates from 2‐(2‐hydroxyphenyl)‐1H‐imidazole lead only to three substituted phenyl carbamates (substituents are 4‐CH₃, 4‐NO₂, and 4‐CN). In both cases, no reactivity to imidazole ring was observed again.     

Palladium-catalyzed Arylation of Ureas

Urea arylation with aryl halides in the presence of catalyst precursor Pd₂dba₃-CHCl₃/Xantphos and Cs₂CO₃ in dioxane at 100°C affords symmetrical N,N'-diarylureas in 64-92% yield. With the same catalytic system the reaction between N-phenylurea and aryl bromides containing electron-withdrawing substituents in the para-position provided N-aryl-N'-phenylureas in 64-91% yields.     

N‐Heterocyclic Carbene–Palladium Complexes as Efficient Catalysts for the Oxidative Carbonylation of Amines to Ureas

A highly efficient oxidative carbonylation reaction of amines to ureas was developed making use of carbene–palladium complexes in the absence of any promoter. Both aliphatic amines and aromatic amines were transformed in good to excellent yields to the expected ureas.     

Synthesis of Unsymmetrical Ureas and S‐Thiocarbamates under Catalyst‐free Conditions in a [BMIM]BF4 Ionic Liquid

Unsymmetrical ureas and S‐thiocarbamates were prepared in good to excellent yields by direct condensation of phenylurea with amines and thiols in 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIM]BF₄) without the addition of any additives. The [BMIM]BF₄ ionic liquid is a mild medium and can be recycled and reused several times.     

Unusual Stability despite a P‐bonded Proton: Phospha and Diphospha Ureas with the TrtP(H)‐Moiety

As the first diphospha‐urea with P‐bonded protons, [TrtP(H)]₂C=O ( 3 ) was found to be of amazing stability, which is thought to be due to the presence of the triphenylmethyl groups. Unlike known cyclic or non‐cyclic analogues, 3 showed next to no tendency to eliminate carbon monoxide. 3 was obtained by reaction of the dimeric phospha‐isocyanate (TrtPCO)₂ ( 1 ) with LiAlH₄, in which the intermediary phosphaalkene 2 was observed. Caused by its two asymmetric phosphorus atoms, 3 appeared as a mixture of two isomers, meso‐3 and rac‐3 (ratio: 20 : 1). Theoretical considerations, and the analysis of the proton‐coupled ³¹P NMR spectrum (spin system: AA′XX′), allowed the assignment of the signals to the two isomers. The action of anhydrous hydrogen chloride on 3 led to the cleavage of one P–C(:O)‐bond, and formation of an equimolar mixture of TrtPH₂ ( 5 ) and TrtP(H)C(:O)Cl ( 6 ). Cleavage of a P–C(:O)‐bond in 3 was also observed in its reaction with tetramethylguanidine (TMG) or ammonia. As proved by ³¹P NMR spectroscopy in the case of TMG, the reaction proceeded via the phosphaalkene intermediate 8 . Acting as nucleophiles, TMG and ammonia substituted TrtP(H) in 3 , and the P,N‐ureas 9 and 10 , with TrtPH₂ ( 5 ) as a side product, were obtained.     

Investigation of Steric Influences on Hydrogen‐Bonding Motifs in Cyclic Ureas by Using X‐Ray,Neutron, and Computational Methods

A series of urea‐derived heterocycles, 5N‐substituted hexahydro‐1,3,5‐triazin‐2‐ones, has been prepared and their structures have been determined for the first time. This family of compounds only differ in their substituent at the 5‐position (which is derived from the corresponding primary amine), that is, methyl ( 1 ), ethyl ( 2 ), isopropyl ( 3 ), tert‐butyl ( 4 ), benzyl ( 5 ), N,N‐(diethyl)ethylamine ( 6 ), and 2‐hydroxyethyl ( 7 ). The common heterocyclic core of these molecules is a cyclic urea, which has the potential to form a hydrogen‐bonding tape motif that consists of self‐associative (8) dimers. The results from X‐ray crystallography and, where possible, Laue neutron crystallography show that the hydrogen‐bonding motifs that are observed and the planarity of the hydrogen bonds appear to depend on the steric hindrance at the α‐carbon atom of the N substituent. With the less‐hindered substituents, methyl and ethyl, the anticipated tape motif is observed. When additional methyl groups are added onto the α‐carbon atom, as in the isopropyl and tert‐butyl derivatives, a different 2D hydrogen‐bonding motif is observed. Despite the bulkiness of the substituents, the benzyl and N,N‐(diethyl)ethylamine derivatives have methylene units at the α‐carbon atom and, therefore, display the tape motif. The introduction of a competing hydrogen‐bond donor/acceptor in the 2‐hydroxyethyl derivative disrupts the tape motif, with a hydroxy group interrupting the N? H???O?C interactions. The geometry around the hydrogen‐bearing nitrogen atoms, whether planar or non‐planar, has been confirmed for compounds 2 and 5 by using Laue neutron diffraction and rationalized by using computational methods, thus demonstrating that distortion of O‐C‐N‐H torsion angles occurs to maintain almost‐linear hydrogen‐bonding interactions.     

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.     

NIS/PhI(OAc)2‐Mediated Diamination/Oxidation of N‐Alkenyl Formamidines: Facile Synthesis of Fused Tricyclic Ureas

Facile synthesis of bicyclic ureas by NIS/PhI(OAc)₂‐mediated diamination/oxidation of N‐alkenyl formamidines is reported. Bulky aromatic groups such as 2,6‐diisopropylphenyl and mesityl and alkyl groups were tolerated towards the process. Several control experiments have been performed, and the reaction outcomes indicate that the oxidation process is probably concerted with the diamination cyclization, and succinimide generated from NIS‐mediated aminoamidiniumation step promoted the PhI(OAc)₂‐mediated oxidation step. The new methodology provides an efficient method for the synthesis of fused tricyclic ureas.     

催化选择氧化还原羰基化合成脲*

本文概述了胺硝基物选择氧化还原羰基化生成脲的新工艺路线。对催化剂体系、羰基化反应机理和反应的选择性作了比较全面的评述,着重介绍了金属钯和非金属硒催化的选择氧化还原羰基化反应合成对称脲、非对称脲和环脲,讨论了该方法的应用前景。     

Ureas as a New Nucleophilic Reagents for SNAr Amination and Carbamoyl Amination Reactions in 1,3,7‐Triazapyrene Series

The ability of urea anions to react as nucleophiles with alkoxy derivatives of 1,3,7‐triazapyrenes has been investigated. It was found that against all expectations, the products of the substitution of an alkoxy groups (S_N^ipso ) by amino group were isolated in good yields. The reactions proceed in anhydrous dimethyl sulfoxide solution at room temperature. But when anions of the mono‐substituted ureas containing bulky substituents were used, the first products of the earlier unknown S_NAr reactions of alkyl carbamoyl amination were obtained.