Sequential Addition Reactions Research Articles

Concise Chemistry of Urea Formaldehyde Resins and Formaldehyde Emission

Urea formaldehyde (UF) resins have found a lot of industrial applications mostly as binder in woodworks and coating. The resin is a low-cost product synthesized from urea and formaldehyde in a sequential addition (methylolation) and condensation (polymerization) reactions. The addition reaction generates methylol and urea derivatives that proceed into condensation reactions. The condensation reactions takes the resin from its initial fluid state through to the formation of a thermosetting film, however, this is companied by release of formaldehyde which may be hazardous to health. As briefly highlighted in this review, having a concise knowledge of the chemistry of these processes will be an easy guide towards a successful synthesis of UF resins with improved performance and environmental attributes.

Rapid access to 3-indolyl-1-trifluoromethyl-isobenzofurans by hybrid use of Lewis/Brønsted acid catalysts.

We report herein a rapid access to 3-indolyl-1-trifluoromethyl-isobenzofurans via a [1,4]-hydride shift/cyclizatin/intermolecular nucleophilic addition reaction sequence. In this process, a Lewis acid promoted internal redox reaction ([1,4]-hydride shift/cyclization) followed by a Brønsted acid promoted intermolecular reaction (generation of cyclic oxonium cation/intermolecular Friedel-Crafts reaction) occurred to give various 3-indolyl-1-trifluoromethyl-isobenzofurans in good chemical yields.

Highly Functionalized Cyclohexenes Derived from Benzene: Sequential Tandem Addition Reactions Promoted by Tungsten.

The dihapto-coordination of benzene to the π-basic fragment {TpW(NO)(PMe3)} (Tp = hydridotris(pyrazolyl)-borate) enhances the basicity of the arene ligand to the point that it can be protonated with a mild Brønsted acid (diphenylammonium triflate; p Ka ∼ 1). The resulting η2-benzenium complex reacts with a wide range of nucleophiles including protected enolates, cyanide, amines, methoxide, and aromatic nucleophiles to form 5-substituted 3,4-η2-1,3-cyclohexadiene complexes in good yield (42-70%). These coordinated dienes were successfully taken through a second protonation and nucleophilic addition with a similar scope of nucleophiles (54-80%). The resulting cis-3,4- and cis-3,6-disubstituted η2-cyclohexene complexes were prepared with high regio- and stereocontrol, as governed by the asymmetric nature of π-allyl intermediates. In some cases, a diene linkage isomerization from 3,4-η2 to 1,2-η2 could be effected with a redox catalyst, and reactions of the latter species led to cis-3,5-disubstituted cyclohexene products exclusively. Oxidative decomplexation afforded the free cyclohexene products in moderate yield (37-68%). Additionally, when a single enantiomer of the chiral dearomatization agent was used, the elaborated cyclohexenes were able to be synthesized in enantioenriched forms (86-90% enantiomeric excess). Full characterization of 40 new compounds is provided that includes two-dimensional NMR, IR, electrochemical and in some cases crystallographic data.

A new synthetic pathway based on one-pot sequential aza-Michael addition and photoCuAAC click reactions.

A solvent-free process is described for the synthesis of tailor-made molecules from a one-pot, two-step approach combining aza-Michael addition and photoinduced copper(i) catalysed azide–alkyne (photo-CuAAC) reactions. After the first reaction between an amine and an acrylate, cycloaddition between an azide and an alkyne is activated by light irradiation in the presence of a copper complex. The kinetics of the aza-Michael addition and photo-CuAAC reaction were investigated by liquid state 1H NMR spectroscopy and real-time Fourier transform infrared spectroscopy. This new process represents a well-defined spatio-temporal pathway to the synthesis of bespoke intermediate molecules for various applications.

Diastereoselective Synthesis of Tetrahydroquinolines via [4 + 2] Annulation between in Situ Generated p-Quinone Methides and Nitroalkenes.

A formal [4 + 2] annulation reaction between in situ generated p-quinone methides and nitroalkenes via an aza-Michael/1,6-conjugate addition reaction sequence has been developed in which manganese dioxide is used as the oxidant to promote in situ formation of o-tosylaminophenyl-substituted p-QMs. Under mild conditions, this unprecedented cascade reaction readily occurs in good yield, providing straightforward access to a series of 4-aryl-substituted tetrahydroquinolines.

Sequential Pd2(dba)3 participated C–C bond cleavage of O-bromophenyl cyclobutanones/Michael addition en route to benzospirones

A tandem Pd2(dba)3 participated C–C bond cleavage of O-bromophenyl cyclobutanone derivatives/Michael addition reaction sequence was realized. We disclosed the first intramolecular C–Br bond triggered ring opening reaction of arylcyclobutanones, distinct from related reports in which the reactions were initiated by arylboron, silane or unsaturated chemical motifs, among others. The in situ generated palladium species underwent ring expansion process leading to methyleneindanones, which further reacted with dba to provide benzospirones in one step.

Sulfonyl as a Traceless Activation Group for Enantioselective Mannich Reaction Catalyzed by Thiourea to Access Chiral β-Aminophosphonates

An efficient enantioselective Mannich reaction of N-protected α-sulfones with β-benzenesulfonyl phosphonates was developed by using a chiral cinchona alkaloid-derived thiourea as a catalyst. This method was used to obtain a series of chiral α-sulfonyl-β-aminophosphonates in yields of up to 96% with 89:11 dr and 88% ee. These compounds were further transformed into β-aminophosphonates or chiral azetidines with various functional groups by a Horner–Wadsworth–Emmons/aza-Michael addition reaction sequence.

Synthesis and characterization of poly(N-isopropyl methacrylamide) core/shell nanogels for controlled release of chemotherapeutics

A method is presented for synthesizing and characterizing core/shell nanogels based around poly(N-isopropyl methacrylamide) (PNIPMAAm). The effectiveness of the sequential addition reaction scheme was determined for its impact on temperature response, glass transition temperature, and details of polymer structure as revealed by 1H NMR spectra. PNIPMAAm cores coated with poly(tert-butyl methacrylate) (PTBMA), poly(ethylene glycol phenyl acrylate) (PEGPhA), and poly(phenyl methacrylate) (PPhMA) were characterized for structure and effectiveness as carriers for the model chemotherapeutic Doxorubicin (DOX). Swelling studies showed that the core/shell polymerization significantly decreases the collapse, though had limited impact on the lower critical solution temperature (LCST) of PNIPMAAm. Coating with PEGPhA did impart large variability in the particle size. Proton NMR and DSC confirmed the core/shell structure for all samples; however it proved that PPhMA was less effective at coating the PNIPMAAm nanogel. The core/shell nanogels were then characterized for their application as drug delivery vehicles using DSC, partition coefficient, and drug release studies with DOX. These studies showed that coating PNIPMAAm with PTBMA developed a more effective drug delivery vehicle for hydrophobic drugs like DOX.

Chemical kinetic insights into the ignition dynamics of n-hexane

Normal alkanes constitute a significant fraction of transportation fuels, and are the primary drivers of ignition processes in gasoline and diesel fuels. Low temperature ignition of n-alkanes is driven by a complex sequence of oxidation reactions, for which detailed mechanisms are still being developed. The current study explores the dynamics of low-temperature ignition of n-hexane/air mixtures, and identifies chemical pathways that characterize the combustion process. Two chemical kinetic mechanisms were selected as a comparative study in order to better understand the role of specific reaction sequences in ignition dynamics: one mechanism including a new third sequential O2 addition reaction pathways (recently proposed by Wang et al. 2017), while the other without (Zhang et al. 2015). The analysis is conducted by applying tools generated from the computational singular perturbation (CSP) approach to two distinct ignition phenomena: constant volume and compression ignition. In both cases, the role of the third sequential O2 addition reactions proves to be significant, although it is found to be much more pronounced in the constant volume cases compared to the HCCI. In particular, in the constant volume ignition case, reactions present in the third sequential O2 addition reaction pathways (e.g., KDHP → products + OH) contribute significantly to the explosivity of the mixture; when accounted for along with reactions P(OOH)2 + O2 → OOP(OOH)2 and OOP(OOH)2 → KDHP + OH, they decrease ignition delay time of the mixture by up to 40%. Under HCCI conditions, in the first-stage ignition, the third-O2 addition reactions contribute to the process, although their role decays with time and becomes negligible at the end of the first stage. The second ignition stage is dominated almost exclusively by hydrogen-related chemistry.

One-Pot Synthesis of Charged Amphiphilic Diblock and Triblock Copolymers Via High-Throughput Cu(0)-Mediated Polymerization.

Block copolymers containing functionalized monomers, for example those containing charged groups, can be used for many purposes, one of which is the design of polymeric supramolecular materials based on electrostatic interactions. In this paper the synthesis of diblock copolymers and ABA-triblock copolymers containing poly(n-butyl acrylate) as a first or middle block and poly(2-(dimethylamino)ethyl acrylate), poly(1-ethoxyethyl acrylate) and poly(1-ethoxyethyl-2-carboxyethyl acrylate) as second or outer blocks, resulting in block copolymers that can contain positive or negative charges, is reported. The polymerizations were performed and optimized via one-pot sequential monomer addition reactions via Cu(0)-mediated polymerization using an automated parallel synthesizer. Different initiators, monomer concentrations and polymerization times were tested. While a bromide-containing initiator led to the best results for most monomers, when polymerizing 2-(dimethylamino)ethyl acrylate the use of a chloride-containing initiator was necessary. Due to the slower polymerization using this initiator, a longer polymerization time was needed before addition of the second monomer. Using the optimized conditions, the diblock and triblock copolymers could be synthesized with good control over molecular weight and dispersities around 1.1 were obtained.

Expedited Synthesis of Matrine Analogues through an Oxidative Cascade Addition/Double‐Cyclization Radical Process

The addition of a nicotinate–xanthate derivative to N‐allylindoles and N‐allylpyrroles resulted in polycyclic heterocycle‐fused pyridonaphthyridines through a tandem radical intermolecular/intramolecular oxidative addition reaction sequence that created three new C–C bonds and two new rings in a single event. Such polyheterocycles showcase the matrine alkaloid framework and are similar to indole–monoterpenoid natural products.

Rhenium‐Catalyzed Construction of Polycyclic Hydrocarbon Frameworks by a Unique Cyclization of 1,n‐Diynes Initiated by 1,1‐Difunctionalization with Carbon Nucleophiles

AbstractA regioselective cyclization of 1,n‐diynes under rhenium catalysis was developed on the basis of a rare type of 1,1‐difunctionalization of terminal alkynes with carbon nucleophiles, followed by sequential addition reactions of the resulting alkenylrhenium species. The reaction provides an efficient approach to the synthesis of complex cyclopentane‐fused bi‐ and tricycles and spirocycles, which are useful building blocks for the construction of essential frameworks of biologically active compounds as well as functional materials, from simple starting materials by the formation of up to six new carbon–carbon bonds in a single step. The reaction proceeds under neutral conditions and does not require external ligands or additives. The key to this reactivity is the unique activation mode of the rhenium carbonyl complex, which prefers to interact with heteroatoms in polar carbon–heteroatom bonds as well as nonpolar carbon–carbon unsaturated π bonds.

Rhenium‐Catalyzed Construction of Polycyclic Hydrocarbon Frameworks by a Unique Cyclization of 1,n‐Diynes Initiated by 1,1‐Difunctionalization with Carbon Nucleophiles

A regioselective cyclization of 1,n-diynes under rhenium catalysis was developed on the basis of a rare type of 1,1-difunctionalization of terminal alkynes with carbon nucleophiles, followed by sequential addition reactions of the resulting alkenylrhenium species. The reaction provides an efficient approach to the synthesis of complex cyclopentane-fused bi- and tricycles and spirocycles, which are useful building blocks for the construction of essential frameworks of biologically active compounds as well as functional materials, from simple starting materials by the formation of up to six new carbon-carbon bonds in a single step. The reaction proceeds under neutral conditions and does not require external ligands or additives. The key to this reactivity is the unique activation mode of the rhenium carbonyl complex, which prefers to interact with heteroatoms in polar carbon-heteroatom bonds as well as nonpolar carbon-carbon unsaturated π bonds.

ChemInform Abstract: A Single‐Flask Synthesis of Morita—Baylis—Hillman Adducts from Ethoxyacetylene and Carbonyl Compounds: Synthesis of Subamolides D and E.

AbstractLithiation of ethoxyacetylene and sequential addition reaction with aldehydes and/or ketones and BF3·OEt2 leads to 2‐hydroxymethyl enoates in good to excellent overall yields.

Sequential Addition Reaction of Sulfanylmethyllithiums and Grignard Reagents to Thioformamides Leading to the Formation of 2-Phenyl-2-sulfanylethyl Tertiary Amines.

The reaction of sulfanylmethyllithiums generated from benzylsulfanes and n-BuLi with N,N-dimethylthioformamide followed by the addition of Grignard reagents gave 2-phenyl-2-sulfanyl tertiary amines in moderate to good yields. A range of Grignard reagents involving primary alkyl, aryl, vinyl, and alkynyl Grignard reagents were used. Two carbon-carbon bond-forming reactions were achieved through a one-pot reaction. The reaction showed good to high diastereoselectivity, particularly with alkynyl Grignard reagents.

H-atom addition and abstraction reactions in mixed CO, H2CO and CH3OH ices – an extended view on complex organic molecule formation

Complex organic molecules (COMs) have been observed not only in the hot cores surrounding low- and high- mass protostars, but also in cold dark clouds. Therefore, it is interesting to understand how such species can be formed without the presence of embedded energy sources. We present new laboratory experiments on the low-temperature solid state formation of three complex molecules: methyl formate (HC(O)OCH3), glycolaldehyde (HC(O)CH2OH) and ethylene glycol (H2C(OH)CH2OH), through recombination of free radicals formed via H-atom addition and abstraction reactions at different stages in the CO-H2CO-CH3OH hydrogenation network at 15 K. The experiments extend previous CO hydrogenation studies and aim at resembling the physical&chemical conditions typical of the CO freeze-out stage in dark molecular clouds, when H2CO and CH3OH form by recombination of accreting CO molecules and H-atoms on ice grains. We confirm that H2CO, once formed through CO hydrogenation, not only yields CH3OH through ongoing H-atom addition reactions, but is also subject to H-atom-induced abstraction reactions, yielding CO again. In a similar way, H2CO is also formed in abstraction reactions involving CH3OH. The dominant methanol H-atom abstraction product is expected to be CH2OH, while H-atom additions to H2CO should at least partially proceed through CH3O intermediate radicals. The occurrence of H-atom abstraction reactions in ice mantles leads to more reactive intermediates (HCO, CH3O and CH2OH) than previously thought, when assuming sequential H-atom addition reactions only. This enhances the probability to form COMs through radical-radical recombination without the need of UV photolysis or cosmic rays as external triggers.

Vicinal Functionalization of N‐Alkoxyenamines: Tandem Umpolung Phenylation–Nucleophilic Addition Reaction Sequence

AbstractThe vicinal functionalization of N‐alkoxyenamines, derived in situ from aldehydes and isoxazolidines, has been achieved with the formation of two new carbon–carbon bonds by utilizing an organo‐aluminum reagent and subsequent allylmagnesium bromide or tributyltin cyanide as external carbon‐centered nucleophiles. By changing the second carbon nucleophile, various amine derivatives were obtained in good yields.

Group-assisted purification (GAP) chemistry for dihydrofurans: water as a medium for catalyst free synthesis in a one pot four component reaction

A simple, catalyst free, water mediated, one pot four component, green protocol was developed for title compounds 7 starting from aromatic aldehydes (1), malononitrile (2), 1,3-diones (3) and N-chlorosuccinimide (NCS) in a sequential addition reaction at ambient temperature. The approach presented herein, for the first time, is through an unusual rearrangement where NCS was reacted with 2-amino-7,7-dimethyl-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4), which was formed by the Knoevenagel condensation of aldehyde and malononitrile followed by the Michael addition of 3. In addition, this novel protocol is compatible with various aldehydes and active C–H functional derivatives, accomplishes high yields and follows the GAP chemistry principle. Interestingly, compound 4 when reacted with NCS in alcohol medium gave 2-cyano-6,6-dimethyl-4-oxo-3-aryl-2,3,4,5,6,7-hexahydrobenzofuran-2-carboxylate (5).

ChemInform Abstract: Palladium‐Catalyzed Reaction of Arylboronic Acids with Aliphatic Nitriles: Synthesis of Alkyl Aryl Ketones and 2‐Arylbenzofurans.

An efficient palladium-catalyzed addition of arylboronic acids to aliphatic nitriles has been developed, providing a wide range of alkyl aryl ketones in moderate to excellent yields. It is noteworthy that sequential addition and intramolecular annulation reaction of 2-(2-hydroxyphenyl)acetonitriles with arylboronic acids are also conducted smoothly to afford 2-arylbenzofurans in good yields under the standard conditions.

ChemInform Abstract: Highly Efficient Synthesis of 2,3,4‐Trisubstituted Furans via Silver‐Catalyzed Sequential Nucleophilic Addition and Cyclization Reactions of Haloalkynes.

Abstract A regioselective synthesis of 2,3,4-trisubstituted furans using AgNO 3 catalyst from haloalkynes in a one-pot procedure has been reported. The transformation consists of a sequential silver-catalyzed nucleophilic addition and cyclization reaction of haloalkynes. A wide variety of haloalkynes can be used in this chemical process.