A high temperature investigation using microwave synthesis for electronically and sterically disfavoured substrates of the Newman-Kwart rearrangement

Electronically deactivated and/or sterically hindered substrates undergo the Newman-Kwart rearrangement (NKR) at around 300 °C, beyond the range of most convenient and safe, small-scale laboratory equipment. We report here the convenient conversions of several difficult substrates using modern microwave technology, which has proven ideal for investigating this high temperature reaction in all but the most refractory of cases. In addition, several previously reported difficult examples were re-investigated, and found not to require high temperatures under these conditions, for various reasons which are elaborated upon.     

2,4-Bis(fluorocarbon)-substituted phenols for high yield Newman-Kwart rearrangement reactions

The Newman-Kwart thermal rearrangement of two 2,4-disubstituted O-arylthiocarbamates, prepared from the corresponding phenols, is reported. Clean conversion to the S-arylthiocarbamates in high yields was observed. The rearrangement appears to be facilitated by the presence of electron-withdrawing substituents in the 2- and 4-positions of the aromatic ring.     

The Newman-Kwart rearrangement: a microwave kinetic study

The kinetic profile of the Newman-Kwart rearrangement has been evaluated using microwave heating. After first demonstrating equivalence between conventional convective heating and microwave heating, data was gathered and analyzed to determine the effects of substituent, solvent, and concentration on the reaction order. Reaction rate constants, Arrhenius constants, and activation energies have been determined. The reaction rate shows strong sensitivity to the substituent and modest sensitivity to the solvent. At high concentrations, the reaction order increases from the previously reported first-order to a mixed first/second-order reaction. Overall, this re-evaluation of the Newman-Kwart rearrangement has shown the reaction rate order to be more complex than previously thought. In addition, microwave heating has proven ideal for the rapid collection of data to facilitate this type of kinetic study.     

Convenient Synthesis of 1-Thiohydroxypyrene by Newman-Kwart Rearrangement

1-Thiohydroxypyrene(1) and its two intermediates, 1-pyrenyl-O-thiocarbamate(2) and 1-pyrenyl-S-thio- carbamate(3), were synthesized using 1-hydroxypyrene as the starting material. The key synthetic step is Newman-Kwart rearrangement. The results indicate that the Newman-Kwart rearrangement is more effective in suitable solvent than conventional method based on pure organic compound. The structures of compounds 1―3 were characterized by FTIR, NMR, GC-MS and elementary analysis. The crystal structures of two new compounds(2 and 3) were determined by single crystal X-ray diffraction analysis. The whole synthetic process is simple, mild and with high yield.     

Efficient synthesis of functionalized pyrimidones via microwave-accelerated rearrangement reaction

An efficient synthesis of functionalized pyrimidones via microwave-accelerated rearrangement reaction of amidoxime DMAD adducts is described. In most cases, the pyrimidone formation was furnished in reasonable yield after 2 min of microwave irradiation.     

Novel synthesis and rearrangement of 3,1,5-benzoxadiazepines

N,N-Diacyl-o-phenylenediamines react with dibromotriphenylphosphorane in the presence of triethylamine as HBr captor to give 3,1,5-benzoxadiazepines in good yields. If the reaction is carried out without acid acceptor the initially formed 3,1,5-benzoxadiazepine finally rearranges into 1-acylbenzimidazole. It has also been found that the isolated 2,4-dimethyl-3,1,5-benzoxadiazepine rearranges under the influence of hydrogen bromide into 1-acetyl-2-methylbenzimidazole.

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Neue Synthese und Umlagerung des 3,1,5-Benzoxadiazepins

Zusammenfassung Die Umsetzung von N,N-Diacyl-o-phenylendiaminen mit Triphenyldibromphosphoran in Gegenwart von Triethylamin als HBr-bindendes Mittel führt mit guten Ausbeuten zu den 3,1,5-Benzoxadiazepinen. Wird die Reaktion ohne säurebindendes Mittel durchgeführt, dann erleidet das anfänglich entstandene 3,1,5-Benzoxadiazepin eine Umlagerung in 1-Acylbenzimidazol. Es wurde auch gefunden, daß das isolierte 2,4-Dimethyl-3,1,5-benzoxadiazepin unter dem Einfluß des Bromwasserstoffs in 1-Acetyl-2-methylbenzimidazol umgelagert wird.

     

Microwave-assisted aza-Cope rearrangement of N-allylanilines

The aza-Cope rearrangement of N-allylanilines is described. The use of BF₃·OEt₂ and microwave irradiation allows to run the transformation under mild conditions and in reaction times of minutes.     

Ireland-Claisen rearrangement of ynamides: stereocontrolled synthesis of 2-amidodienes

The Ireland-Claisen rearrangement of propargyl ynamido ester substrates is reported. The expected allenamide carboxylic acid products from [3,3]-sigmatropic rearrangement are not isolated, with 2-amidodienes alternatively formed in good yield with high levels of stereocontrol after decarboxylation.     

A homologous enolate Truce-Smiles rearrangement

During preparation of a series of diphenyl ethers it was observed that displacement of an activated aryl fluoride with ortho-hydroxyacetophenone afforded a product that was C-arylated adjacent to the ketone. Evidence suggested this product was formed by Smiles rearrangement of an O-arylated intermediate.     

Traceless synthesis of hydantoin by focused microwave irradiation

An efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 1,3-disubstituted hydantoin has been developed. Chloroacetyl chloride was directly anchored to HO-PEG-OH and subsequently reacted with various primary amines in a microwave cavity. The PEG bound secondary amine coupled with isocyanates and concomitant cyclization-cleavage step occurred in mild basic conditions by microwave flash heating. The desired products were then liberated from the soluble matrix in modest yield and high purity.     

The mercury-mediated decarboxylation (Pesci reaction) of naphthoic anhydrides investigated by microwave synthesis

The mercury-mediated decarboxylation (Pesci reaction) of several substituted naphthoic anhydrides has been investigated by microwave synthesis. A laboratory microwave reactor was found to be ideal for small-scale preparations of this slow reaction, reducing reaction times from typically four days to less than 1 h for the three-step process. The ionic reaction medium rapidly heated to high temperatures under microwave heating and could be efficiently maintained by low microwave power settings. Generation of stoichiometric CO₂ was safely contained within the reaction tubes. A simplified reaction procedure has been developed. For substituted naphthoic anhydrides, ¹H NMR analysis of the naphthoate ester derivatives indicated no change in the regioisomer ratio compared to previously reported thermal values.     

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.     

Microwave promoted oxazole synthesis: cyclocondensation cascade of oximes and acyl chlorides

Microwave irradiation promotes the rapid O,N-acylation-cyclodehydration cascade reaction of oximes and acid chlorides to give oxazoles.     

Fast synthesis of temperature-sensitive PNIPAAm hydrogels by microwave irradiation

A novel method, microwave irradiation synthesis, is proposed for the preparation of thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The PNIPAAm hydrogels were separately synthesized by using microwave irradiation method and water-bath heating method. Chemical groups, lower critical solution temperature (LCST) and surface morphology of these PNIPAAm hydrogels were characterized by FT-IR, DSC and SEM. Swelling ratios of the gels were measured gravimetrically in the temperature range from 10.0 to 60.0 °C. Results showed that (1) the use of microwave irradiation can greatly shorten the reaction time required for PNIPAAm hydrogel synthesis from several hours to several minutes in comparison with water-bath heating method, and obviously improve the yields of the PNIPAAm gels, which were up to 99% after a short reaction time; (2) SEM micrographs and textural measurement revealed that the gels synthesized using microwave irradiation had more porous structure, and their average pore sizes and specific surface areas were larger than those of the gels synthesized using water-bath heating method; and (3) the PNIPAAm hydrogels synthesized using microwave irradiation had much higher swelling ratios at 10.0 °C below the LCST, and had lower swelling ratio at 60.0 °C above the LCST compared to the hydrogels synthesized by water-bath method.     

Novel synthesis of oligosaccharides linked with carbamate and urea bonds utilizing modified Curtius rearrangement

We describe a novel synthesis of various carbamate- and urea-linked disaccharides stereospecifically using sugar carboxylic acids and sugar alcohols or sugar amines by the modified Curtius rearrangement. In this reaction, the reactivity of each hydroxyl group in glucose as an acceptor has been disclosed. Furthermore, we applied this method to the synthesis of carbamate-linked oligosaccharides including a dendritic molecule.     

Facile synthesis of new 1,2,3-benzotriazolo-2-oxo-azetidine analogues by microwave irradiation

A series of new N¹-[3-{(4-subtitutedaryl-3-chloro-2-oxo-azetidine)-carbamyl}-propyl]-1,2,3-benzotriazoles 4(a–s) have been synthesized from 1,2,3-benzotriazole as a starting material by microwave method. The structures of all the synthesized compounds were confirmed by chemical and spectral analyses such as IR, ¹H NMR, ¹³C NMR and FAB-Mass.     

水溶液中微波辅助下5-碘嘧啶类化合物的合成

5-碘嘧啶类衍生物具有显著的化学治疗活性和有机合成用途。碘苷(又名疱疹净)于1962年被美国FDA批准用于治疗疱疹病毒角膜炎,这是第一个抗单纯疱疹病毒药物[1]。以碘苷为中间体可以合成其它高效低毒的抗病毒药物[2]。另外,通过Suzuki、Sonogashira等金属催化偶联反应可以在5位引     

The first approach to a new family of macrocycles: synthesis and characterization of thiacalix[2]thianthrenes

New thianthrene based macrocycles with basket shaped structures were prepared by thermal treatment of tetrakis-(N,N′-dimethylthiocarbamoyl)-tetra-tert-butyl-thiacalix[4]arene. Their structural characterization as well as the study of the formation mechanisms are presented in this article. The influence of the conformation of the starting thiacalixarene on the reaction is also discussed.     

Cold microwave chemistry: synthesis using pre-cooled reagents

A novel experimental procedure for chemical reactions has been devised that involves mixing and then freezing the reagents (organic solvent-free) to a sub-zero temperature such as −30 °C. This frozen mixture is exposed to microwave irradiation for a brief period of time. The use of pre-cooled reagents may give a single product not obtained by traditional microwave irradiation at room temperature. Interestingly, such a product may provide information about mechanisms by identifying the first step of a multiple step reaction.