Substituent-controlled domino-Knoevenagel-hetero Diels-Alder reaction—a one-pot synthesis of polycyclic heterocycles

The reaction of 2-(N-alkenyl-N-aryl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde with dimedone/Meldrum’s acid/4-hydroxycoumarin by heating in ethanol in the presence of pyridine produces polycyclic heterocycles bearing pyridine and pyran rings in a one-pot reaction. The effect of substituents on N-atom of the amino function controls the mode of reaction. Terminal alkenes prefer intramolecular Michael type reaction, but non-terminal alkenes favour Diels-Alder reaction, whereas, under similar condition, 2-(N-alkyl-N-allyl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde undergoes domino-Knoevenagel-hetero Diels-Alder reaction.     

Kinetic parameters of radical reactions of 2-mercaptobenzothiazole with quinone imines

The chain reaction of N,N′-diphenyl-1,4-benzoquinone diimine with 2-mercaptobenzothiazole was studied by two methods developed earlier for the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole. In the methods used, the kinetic scheme of the reaction is simplified by creating conditions under which the rates of all stages except radical generation and decay can be neglected. One of the methods was updated. For the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole, both methods gave close results; for the chain reaction of N,N′-diphenyl-1,4-phenylenediamine with 2-mercaptobenzothiazole, the results differed by approximately one order of magnitude.     

Solid state reaction between p-benzoquinone and dihydroxybenzene

Reaction kinetics of p-benzoquinone-p-dihydroxybenzene; p-benzoquinone-m-dihydroxybenzene and p-benzoquinone-o-dihydroxybenzene systems have been studied in the solid state using capillary, gravimetric, and dilatometric techniques. It is found that p-benzoquinone is the diffusing species. The diffusion occurs through surface migration and depends very much on the symmetry of the dihydroxybenzene molecules. Gravimetric studies indicate that cracks are formed in the product during reaction and that the reaction reaches completion. Dilatometric studies indicate that the reaction products are more compact and contraction in volume takes place during the course of reaction.     

Chiral base-catalyzed aldol reaction of trimethoxysilyl enol ethers: effect of water as an additive on stereoselectivities

An aldol reaction of trimethoxysilyl enol ether catalyzed by lithium binaphtholate is described. The aldol reaction of trimethoxysilyl enol ether derived from cyclohexanone under anhydrous conditions predominantly afforded the anti-aldol adduct with moderate enantioselectivity, whereas the reaction under aqueous conditions predominantly resulted in the syn-adduct and the enantioselectivity of the syn-adduct was considerably improved. The best enantioselectivity was obtained in the reaction of trimethoxysilyl enol ether derived from 1-indanone with cyclohexanecarboxaldehyde (97% ee (syn)). This is the first example of an aldol reaction of trimethoxysilyl enol ether catalyzed by a chiral base.     

Investigation of m-nitroaniline formation during the Zimmermann reaction

The Zimmermann reaction for the determination of 17-ketosteroids was tested under both room-temperature and steam-distillation reaction conditions. meta-Nitroaniline was isolated from the residue of the steam distillation by ether extraction and thin-layer chromatography. Conclusive identification was by infrared spectroscopy. In contrast, m-nitroaniline was not formed under room-temperature reaction conditions, even when allowed to react for 24 hr. Similar results were also obtained for the reaction between acetone and m-dinitrobenzene under alkaline conditions. In conclusion, the results indicate that m-nitroaniline formation cannot account for the conversion of structure I to structure II under room-temperature reaction conditions as investigated herein.     

Rheological study on the cure kinetics of two-component addition cured silicone rubber

The cure kinetics for two-component silicone rubber formed by addition reaction was studied by the rheological method. The influence of reaction temperature (T) on the cure kinetics was explored in detail. It was observed that the data of gel time (t _gel, i.e. the time when the reaction reaches the gel point) or a specific reaction time (t _nc) (defined as the reaction time before which time the influence of confinement of network on the diffusion of reaction components can be neglected) versus T obey certain functional relationship, which was well explained by the cure kinetics model of thermoset network. The cure kinetics for the two-component silicone rubber can be well fitted by the Kamal-Sourour(autocatalyst) reaction model rather than Kissinger model. When the reaction time was before or equal to t _nc, the reaction order obtained by the Kamal-Sourour reaction model was 2, which was consistent with the reaction order inferred from the two components chemical reaction when the diffusion of reaction components was not influenced by the formed cross-linked polymer network. When the reaction time was larger than t _nc, such as to the end of reaction (t _e), the influence of confinement of network on the diffusion of reaction components cannot be neglected, and the reaction order obtained by the Kamal-Sourour reaction model was larger than 2. It was concluded that the confinement effect of network had a greater influence on the cure kinetics of the silicone rubber. The reaction rate constants (k _r) under different temperatures were also determined by Kamal-Sourour reaction model. The activation energy (E) for the two-component silicone rubber was also calculated from the results of lnt _gel, lnt _nc, and lnk _r versus 1/T, respectively. The three values of E were close, which indicated that above analyses were self-consistent.     

Asymmetric synthesis of α,β-substituted γ-amino acids via conjugate addition

The first conjugate addition reaction of organocuprates to N-enoyl oxazolidinone where a N-protected γ-nitrogen atom and an α-methyl group are present into α, β-unsaturated system is described. This reaction gave anti-products in moderate yields and high diastereomeric ratios. The anti-products have two contiguous stereogenic centers, one formed by the conjugate addition reaction and the other by a diastereoselective protonation reaction. The removal of chiral oxazolidinone moiety and N-deprotection of amino group furnished chiral α, β-disubstituted γ-amino acids.     

Isocyanide based multicomponent reactions of oxazolidines and related systems

N-Alkyloxazolidines react in a multicomponent reaction with carboxylic acids and isocyanides to give N-acyloxyethylamino acid amides. The previously reported reaction conditions were improved using a design of experiments approach (DoE). Under the optimised conditions, good yields of the N-acyloxyethylamino acid amide products are obtained both via a three- or four-component approach from N-alkylethanolamines, aldehydes/ketones, isocyanides and carboxylic acids. The reaction of oxazolidines without a nitrogen substituent was found to give either the expected Ugi products or the N-acyloxyethylamino acid amides depending on the choice of reaction conditions. Optimised reaction conditions were also developed for the ring-expansion of oxazolidines to morpholin-2-ones via reaction with an isocyanide followed by hydrolysis. The mechanistic pathway of the multicomponent reaction was briefly investigated using an ¹⁸O labelling experiment. The carboxylic acid component can be replaced by a range of other acidic nucleophiles including thiobenzoic acid, thiophenol or 5-phenyltetrazole, which are incorporated via an alternative pathway. These latter reactions can also be applied to 2-aminotetrahydrofurans, 2-aminotetrahydropyrans or 4-hydroxybut-2-one, further extending the structural diversity of the multicomponent reaction products.     

Stereoselective total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (−)-(6S,2′S)-epi cryptocaryalactone via asymmetric acetate aldol reaction

The total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (?)-(6S,2′S)-epi cryptocaryalactone is reported based on asymmetric acetate aldol reaction. Still–Gennari reaction, Evans acetal intramolecular oxa-Michael reaction and lactonisation are the key steps in the target synthesis.     

Reactions of N,N-dimethylamino(diphenylphosphoryl)chloromethane with alkan-2-ones

The direction of the reaction of N,N-dimethylamino(diphenylphosphoryl)chloromethane with alkan-2-ones depends on the ketone structure. N,N-Dimethylamino(diphenylphosphoryl)-chloromethane reacts with linear alkan-2-ones following the Abramov-type reaction to give α-phosphorylated alcohols, while the reaction with branched alkan-2-ones and acetophenone proceeds as the Mannich-type reaction affording the phosphorylated Mannich bases.     

A mild and efficient synthesis of a chiral pyridazinone derivative

We found a mild and efficient reaction condition for construction of a chiral 5-methyl-4,5-dihydropyridazin-3(2H)-one from a chiral β-methyl γ-ketocarboxylic acid via the corresponding acid hydrazide without racemization. Furthermore, we demonstrated that this two-step reaction can be attained by one-pot reaction. This method could be applied to various kinds of substrates because of the mild reaction conditions.     

Application of ortho-chloro-β-aroylthioamides in synthesis(II): an efficient one-pot, three-component synthesis of tricyclic thiochromeno[2,3-b]pyridine derivatives

Tricyclic thiochromeno[2,3-b]pyridine derivatives have been successfully synthesized in an unusual one-pot multicomponent cascade reaction from ortho-halo-β-aroylthioamides, Meldrum's acid, and aromatic aldehydes. The reaction presumably proceeds via Knoevenagel condensation-Michael addition-cyclocondensation-decarboxylation-rearrangement-intramolecular S_NAr reaction sequence. High bond forming efficiency of this reaction makes it attractive for the synthesis of thiochromeno[2,3-b]pyridine derivatives in a single step operation.     

Synthesis of fluorinated imines and carbodiimides from azides via aza-Wittig reaction

The Staudinger reaction of fluoroalkylazides were studied. A series of N-fluoroalkylimines were synthesized via aza-Wittig reaction of N-fluoroalkyliminophosphoranes. The N,N′-difluoroalkylated carbodiimide was also synthesized via the reaction of N-fluoroalkyliminophosphoranes with carbon dioxide or carbon disulfide.     

Isothermal cure kinetics of uncatalyzed and catalyzed diglycidyl ether of bisphenol-A/carboxylated polyester hybrid powder coating

The thermal cure behavior of diglycidyl ether bisphenol-A/carboxylated polyester hybrid powder coating system in the absence and presence of catalyst was monitored using differential scanning calorimetry. Curing temperatures were between 160 and 200?°C. The experimental results showed an autocatalytic behavior of the reaction, which could be described by the model proposed by Kamal. This model includes two rate constants k ₁ and k ₂ and two reaction orders m and n. The activation energies E _a1 and E _a2 of these rate constants were 51.7 and 42.3?kJ/mol for uncatalyzed cure reaction and 40.6 and 35.0?kJ/mol for externally catalyzed reaction. The average order of the overall reaction was found to be 2.45 and 2.72 for uncatalyzed and catalyzed system, respectively. Except for the late stage of cure reaction, the model agreed well with the experimental data, especially at high temperatures and in externally catalyzed cure reaction. A diffusion factor was introduced into the model to account for the effect of diffusion on the cure rate. The modified model greatly improved the predicated data at the late stage of cure reaction.     

Convenient synthesis and unusual reactivity of 2-oxo-2H,5H-pyrano[3,2-c]chromenes

The reaction of 4-oxo-4H-chromen-3-carbaldehydes with coumarin-4-acetic acids under the Perkin conditions follows an interesting pathway that involves aldol reaction and subsequent intramolecular lactonization to afford 2-oxo-2H,5H-pyrano[3,2-c]chromene skeleton. In contrast to chromone-3-carbaldehydes, the same reaction with chromone-2-carbaldehydes yielded only the aldol condensation product. The reaction was performed under thermal and microwave conditions. The reactivity of 2-oxo-2H,5H-pyrano[3,2-c]chromenes in water, alcohol and acetic acid was described.     

N-Allyl-1,3-oxazines via a facile keto-ene/cyclization tandem reaction

The intramolecular keto-ene/cyclization tandem reaction of γ-N-allylamino ketones is an effective means of producing 1,3-oxazines. The reaction usually requires high temperatures and/or pressures. We discovered that N,N-diallyl amines undergo the reaction at lower temperatures than their monoallyl analogs. An extreme example, 1-N,N-diallylamino-9,10-anthraquinone, undergoes the keto-ene reaction near ambient temperature. In the case of 1-N,N′-dialkylaminoanthraquinones, electron deficient ene components can even be used, allowing the preparation of a broad spectrum of oxazines. Furthermore, the N-allyl-1,3-oxazine can be easily deallylated to produce a 1,3-oxazine that contains a secondary amine.     

Temperature vs. time sequences to palliate deactivation in parallel and in series-parallel with the main reaction: parametric study

The calculation of temperature vs. time sequences to palliate catalyst deactivation in an integral reactor has been studied either by maintaining constant the conversion at the reactor outlet in a simple reaction or by maintaining constant the concentration of a given component at the outlet in a complex reaction system. The experimental systems studied, which are a simple one (dehydration of 2-ethylhexanol) and a complex one (isomerization of cis-butene), have kinetic models of the Langmuir-Hinshelwood-Hougen-Watson type for the main reaction and deactivation, with deactivation by coke dependent on the concentration of the reaction components. In the reaction of dehydration of 2-ethylhexanol deactivation occurs in parallel with the main reaction and in the isomerization of cis-butene deactivation occurs in series-parallel with the main reaction. A parametric study has been carried out for both reaction systems. The sequences calculated have been experimentally proven in an automated reaction apparatus.     

Regioselective synthesis of 2-carbonyl furans in a one pot three component reaction

Regioselective synthesis of 2-benzoyl-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-ones have been accomplished through a novel protocol involving β-amino enone, N-chlorosuccinimide and dimedone in a one pot catalyst-free reaction at an ambient temperature. On the other hand, the same reaction when conducted with two equivalents of N-chlorosuccinimide under similar reaction conditions, exclusive formation of 2-benzoyl-3-(dimethylamino)-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-ones were observed. Simple and metal-free reaction conditions, selective product formation and excellent yields are the advantages of this protocol.     

Verbanone in the synthesis of amidoketones from o-menthane series

A verbanone reaction with acetonitrile under Ritter reaction conditions led to a selective formation of o-menthane derivatives, a mixture of stereoisomeric cis-and trans-8-acetamido-o-menthones. The streoisomers ratio depends on the reaction conditions and the character of acid catalyst used.     

Synthesis of important β-functionalized 5-methyl-1H-pyrazol-3-ol derivatives in the presence of γ-alumina catalyst in aqueous medium

The γ-alumina catalyzed synthesis of a new series of β-functionalized 5-methyl-1H-pyrazol-3-ol derivatives by the multi-component reaction of an aldehyde, ethylcyano acetate, and in situ generated 3-methyl-1H-pyrazol-5(4H)-one obtained from hydrazine monohyrade and ethyl acetoacetate in aqueous medium is described. The present reaction forms an important variant of the Yonemitsu-type multi-component reaction. The salient features of this present environmentally benign method are: recyclability of the catalysts, mild reaction condition, excellent yields of product, and the use of aqueous medium in the reaction.