PTSA-catalyzed Mannich-type-cyclization-oxidation tandem reactions: one-pot synthesis of 1,3,5-substituted pyrazoles from aldehydes, hydrazines and alkynes

A convenient one-pot Mannich-type-cyclization-oxidation tandem process has been developed for the synthesis of 1,3,5-trisubstituted pyrazoles derivatives from aldehydes, hydrazines and alkynes using p-toluenesulfonic acid monohydrate (PTSA) as a multifunctional catalyst. This method provides a flexible and rapid route to 1,3,5-trisubstituted pyrazoles.     

Divergent reactivity of α-oximino carbenoids: facile access to 2-isoxazolines and 2H-azirines

Mild catalytic reaction conditions for the synthesis of 2-isoxazolines and 2H-azirines have been developed via carbenoids derived from α-oximino diazo compounds. This has been utilized in the one-pot synthesis of pyrroles in the presence of 1,3-dicarbonyl compounds.     

Chemistry of Phosphorus Ylides. Part 40. Synthesis of Pyrazoles by the [3 + 2] Cycloaddition of Diazo Compounds with Wittig Reagents as Antimicrobial Compounds

A comparative study between the reactions of active phosphacumulenes and stabilized phosphonium ylides on some diazo compounds have been performed. A number of substituted phosphanylidene spiro pyrazoles have been synthesized from the reaction of the active phosphacumulenes and the diazo derivatives. On the other hand, treatment of the diazo substrates with the stabilized phosphonium ylides led to the formation of the corresponding ylidenes and diazenyl phosphanylidenes. The antimicrobial activities for the new compounds are also reported.     

Iodine-Mediated One-Pot Synthesis of 1,4,5-Substituted Pyrazoles from MBH Acetates via Allyl Hydrazone Intermediate

Herein, we report the regioselective one-pot synthesis of 1,4,5-trisubstituted pyrazoles by reacting Morita-Baylis-Hillman (MBH) acetates derived from aryl aldehydes with alkyl or aryl hydrazines in the presence of iodine under aerobic conditions. The reaction proceeds through sequential S_N2′ nucleophilic substitution of substituted hydrazine onto the MBH acetate, I₂-catalyzed oxidation of the allylic hydrazine to allylic hydrazone, heating-induced intramolecular aza-Michael reaction and cyclization, and oxidative aromatization. The key intermediate, the s-trans allyl hydrazones were isolated in good yields by performing the reactions at room temperature. However, the allyl hydrazones prepared from the MBH acetates of aliphatic aldehydes did not furnish the pyrazole owing to the absence of an activated methylene group in the substrate. The synthetic applications of the pyrazoles in Ugi reactions, decarboxylative halogenation, Pd-catalyzed benzoylation of the N-aryl ring, and metal-free tetrazole synthesis has been demonstrated.     

The rhodium catalyzed three-component reaction of diazoacetates, titanium(IV) alkoxides and aldehydes

The rhodium(II)-catalyzed three-component reaction of diazoacetates, titanium alkoxides and aldehydes is shown to give alpha-alkoxyl-beta-hydroxyl acid derivatives; the novel C-C bond formation reaction is proposed to occur through oxonium ylides derived from diazo compounds and titanium alkoxides, and followed by intermolecular trapping by aldehydes.     

Diazocarbonyl and Related Compounds in the Synthesis of Azoles

Diazocarbonyl compounds have found numerous applications in many areas of chemistry. Among the most developed fields of diazo chemistry is the preparation of azoles from diazo compounds. This approach represents a useful alternative to more conventional methods of the synthesis of azoles. A comprehensive review on the preparation of various azoles (oxazoles, thiazoles, imidazoles, pyrazoles, triazoles, and tetrazoles) from diazocarbonyl and related compounds is presented for the first time along with discussion of advantages and disadvantages of «diazo» approaches to azoles.     

Gold(I)‐Catalyzed Diazo Cross‐Coupling: A Selective and Ligand‐Controlled Denitrogenation/Cyclization Cascade

An unprecedented gold‐catalyzed ligand‐controlled cross‐coupling of diazo compounds by sequential selective denitrogenation and cyclization affords N‐substituted pyrazoles in a position‐switchable mode. This novel transformation features selective decomposition of one diazo moiety and simultaneous preservation of the other one from two substrates. Notably, the choice of the ancillary ligand to the gold complex plays a pivotal role on the chemo‐ and regioselectivity of the reactions.     

Safe and Facile Access to Nonstabilized Diazoalkanes Using Continuous Flow Technology

Despite the high synthetic potential of nonstabilized diazo compounds, their utilization has always been hampered by stability, toxicity, and safety issues. The present method opens up access to the most reactive nonstabilized diazoalkanes. Among diazo compounds, nonstabilized alkyl diazo compounds are the least represented because of their propensity to degrade during preparation. The continuous flow oxidation process of hydrazones on a silver oxide column afforded an output stream of base‐ and metal‐free pure diazo solution in dichloromethane. Starting from innocuous ketones and aldehydes, this methodology allows the production of a broad range of unprecedented diazoalkanes compounds in excellent yields, while highlighting their synthetic potential and the possibility of safe large‐scale diazo production.     

Coupling reaction of alkyl chlorides with silyl enolates catalyzed by indium trihalide

Indium(III) halide catalyzed not only the coupling of alkyl chlorides with silyl enolates derived from esters, ketones, and aldehydes to give a variety of alpha-alkylated carbonyl compounds but also one-pot, three-component reactions of aldehyde enolate, alkyl chloride, and allylsilane or alkynylsilane.     

A Convenient Preparation of Diazo Carbonyl Compounds Under Tri-Phase Phase-Transfer Catalysis Conditions

A simple and convenient one-pot preparation method for pure diazo carbonyl compounds under tri-phase phasetransfer catalysis conditions is described.     

One-Pot Synthesis of New,Biologically Active 3,5-Disubstituted-1,2,4-oxadiazoles

New chiral 3,5-disubstituted-1,2,4-oxadiazoles have been prepared via an efficient one-pot procedure by the condensation of new chiral amidoximes derived from amino acids with aldehydes. This method is applicable to both aliphatic and aromatic aldehydes, leading easily to the corresponding pure oxadiazoles in excellent yields. These new compounds were tested for their antibacterial and antifungal activities using microdilution tests against some strains of bacteria and fungi, and they showed excellent antibacterial activity.     

Synthesis of pyrazoles and indazoles from aliphatic diazo compounds (review)

The literature data on the synthesis of indazoles and pyrazoles from aliphatic diazo compounds and compounds containing a carbon-carbon triple bond are reviewed. The dependence of the direction of the reaction and the yields of the final products on the structures of the reagents is discussed. The rearrangements that accompany cycloaddition are examined. Modern views of the mechanisms of the reactions discussed in the review are presented.Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 5, pp. 579–597, May, 1978.     

Morpholine triflate promoted one-pot,four-component synthesis of dihydropyrano[2,3-c] pyrazoles

A one-pot,four-component reaction of ethyl acetoacetate,hydrazine hydrate,aldehydes,and malononitrile was discussed using Lewis acid catalyst morpholine triflate (MorT) to afford a series of dihydropyrano[2,3-c] pyrazoles,which were generally catalyzed by organic alkalis.Moderate to excellent yields,no chromatographic purification,and evasion of environmentally hazardous solvents in the reaction process make this protocol very useful for academia and industry.     

Generation of phosphoranes derived from phosphites. A new class of phosphorus ylides leading to high E selectivity with semi-stabilizing groups in Wittig olefinations

Tosylhydrazones derived from aryl aldehydes react with t-BuOK, ClFeTPP, (MeO)3P, and aldehydes to furnish olefins with high E selectivity. These reactions occur through a Wittig-type pathway via the corresponding diazo compounds, metal carbenes and phosphorous ylides, with the water-soluble trimethyl phosphate as the byproduct. Similar reactions can also be performed using ethyl diazoacetate; however, high E selectivity was only observed in the presence of LiBr. In this case, the reaction is believed to occur via the phosphonate anion, formed through an Arbuzov reaction. Thus this olefination reaction occurs through a Horner-Wadsworth-Emmons (HWE) reaction but the phosphonate anion is generated under completely base-free conditions.     

An efficient, inexpensive, and shelf-stable diazotransfer reagent: imidazole-1-sulfonyl azide hydrochloride

The design and synthesis of a new diazotransfer reagent, imidazole-1-sulfonyl azide hydrochloride, are reported. This reagent has proven to equal triflyl azide in its ability to act as a "diazo donor" in the conversion of both primary amines into azides and activated methylene substrates into diazo compounds. Crucially, this reagent can be prepared in a one-pot reaction on a large scale from inexpensive materials, is shelf-stable, and is conveniently crystalline.     

One-pot, two-step conversion of aldehydes to phosphonyl- and sulfonylpyrazoles using bestmann-ohira reagent

A one-pot, two-step, three-component method for the conversion of commercially available aldehydes to phosphonylpyrazoles has been developed, demonstrating, for the first time, the dual reactivity of the Bestmann-Ohira reagent (BOR) in a single-pot transformation. This method, extended to the synthesis of sulfonylpyrazoles by employing BOR in the first step and a diazomethyl sulfone in the second step, is complementary, with regard to regioselectivity, to the previous methods for the synthesis of such functionalized pyrazoles.     

N-Phenacylpyridinium bromides in the one-pot synthesis of 2,3-dihydrofurans

A one-pot three-component process for the synthesis of highly functionalized 2,3-dihydrofurans from 1,3-dicarbonyl compounds, aromatic aldehydes, and N-phenacylpyridinium bromides has been developed. Benzylidene 1,3-dicarbonyl compounds could be generated in situ from aromatic aldehydes and 1,3-dicarbonyl compounds and then reacted smoothly with N-phenacylpyridinium bromides to produce 2,3-dihydrofurans in moderate to good yields. Piperidine/acetonitrile is the optimal condition for this process. To increase the efficiency of this reaction, this one-pot process was also conducted solvent-free under classical heating conditions and grinding conditions.     

磷酸氢二钾催化多组分一锅法反应合成1,4-二氢吡喃并[2,3-c]吡唑衍生物

绿色、简便、高效的催化四组分反应合成吡喃并[2,3-c]吡唑类杂环化合物是当今有机化学领域的研究热点。 本文发展了在水与聚乙二醇(PEG-200)的混合液中,廉价易得的磷酸氢二钾(K₂HPO₄·3H₂O)催化乙酰乙酸乙酯、水合肼、芳香醛和丙二腈的多组分“一锅法”反应,合成一系列1,4-二氢吡喃并[2,3-c]吡唑-5-腈衍生物,产率为88%~98%。 该方法避免了使用复杂昂贵的催化剂和繁琐的纯化过程。     

Fluorogenic Strain‐Promoted Alkyne–Diazo Cycloadditions

Fluorogenic reactions, in which non‐ or weakly fluorescent reagents produce highly fluorescent products, are attractive for detecting a broad range of compounds in the fields of bioconjugation and material sciences. Herein, we report that a dibenzocyclooctyne derivative modified with a cyclopropenone moiety (Fl‐DIBO) can undergo fast strain‐promoted cycloaddition reactions under catalyst‐free conditions with azides, nitrones, nitrile oxides, as well as mono‐ and disubstituted diazo‐derivatives. Although the reaction with nitrile oxides, nitrones, and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H‐pyrazole derivatives that exhibited an approximately 160‐fold fluorescence enhancement over Fl‐DIBO combined with a greater than 10 000‐fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H‐pyrazoles, which are formed by reaction with disubstituted diazo‐derivatives, is likely due to the presence of energetically low‐lying (n,π*) states. The fluorogenic probe Fl‐DIBO was successfully employed for the labeling of diazo‐tagged proteins without detectable background signal. Diazo‐derivatives are emerging as attractive reporters for the labeling of biomolecules, and the studies presented herein demonstrate that Fl‐DIBO can be employed for visualizing such biomolecules without the need for probe washout.     

In(OTf)3 catalysed simple one-pot synthesis of α-amino phosphonates

A new efficient one-pot synthesis of α-amino phosphonates derived from nitro substituted anilines, aldehydes and diethyl phosphite has been carried out by employing 5 mol% of In(OTf)₃. The method is equally effective for the generation of α-amino phosphonates from various carbonyl compounds and other amines.