A borrowing hydrogen methodology: palladium-catalyzed dehydrative N-benzylation of 2-aminopyridines in water

organic chemistry, spectroscopy, SYNTHESIS Comments Off

Jul 042018

Graphical abstract: A borrowing hydrogen methodology: palladium-catalyzed dehydrative N-benzylation of 2-aminopyridines in water

A borrowing hydrogen methodology: palladium-catalyzed dehydrative N-benzylation of 2-aminopyridines in water

Hidemasa Hikawa,*^a Hirokazu Imamura,^a Shoko Kikkawa^a and Isao Azumaya*^a

Author affiliations

*Corresponding authors

^aFaculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Japan
E-mail: hidemasa.hikawa@phar.toho-u.ac.jp, isao.azumaya@phar.toho-u.ac.jp

Image result for Hidemasa Hikawa Toho University

Isao Azumaya

Abstract

We demonstrate a greener borrowing hydrogen methodology using the π-benzylpalladium system, which offers an efficient and environmentally friendly dehydrative N-monobenzylation of 2-aminopyridines with benzylic alcohols in the absence of base. The crossover experiment using benzyl-α,α-d₂ alcohol and 3-methylbenzyl alcohol afforded H/D scrambled products, suggesting that the dehydrative N-benzylation in our catalytic system involves a borrowing hydrogen pathway. KIE experiments show that C–H bond cleavage at the benzylic position of benzyl alcohol is involved in the rate-determining step (KIE = 2.9). This simple base-free protocol can be achieved under mild conditions in an atom-economic process, affording the desired products in moderate to excellent yields.

N-Benzylpyridin-2-amine 3a 1 Yield 165 mg (90%) as a white solid; mp 90-91 C; IR (KBr) (cm-1) 3226, 3029, 1600, 1575; 1H NMR (400 MHz, CDCl3):  4.50 (d, J=5.7 Hz, 2H), 4.95 (brs, 1H), 6.36 (dt, J=8.5, 0.9 Hz, 1H), 6.58 (ddd, J=7.1, 5.0, 0.9 Hz, 1H), 7.23-7.36 (m, 4H), 7.39 (dd, J=8.7, 7.1, 1.8 Hz, 1H), 8.09 (ddd, J=5.0, 1.8, 0.9 Hz, 2H); 13C-NMR (100 MHz, CDCl3): 46.3, 106.8, 113.1, 127.2, 127.4, 128.6, 137.5, 139.2, 148.2, 158.6; MS (FAB): m/z 185 [M+H]+ .

/////////////borrowing hydrogen methodology, palladium-catalyzed, dehydrative N-benzylation, 2-aminopyridines,

Catalysts for assymetric alkylation and isomerisation reactions

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Jun 042018

+91- 999-997-2051

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+91- 999-997-2051

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Axay Parmar

Founder at Synthesis with Catalysts Pvt. Ltd, axayrp@gmail.com

Basu Agarwal and Dr Razi Abdi

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Synthesis with Catalysts Pvt Ltd was founded with an aim to help aromatic chemical, essential oil, pharmaceutical, API manufacturers to develop new products, increase productivity and improve production methodologies.

We have an advanced research and development centre where we innovate new chemical processes and improve the existing ones and help our customers implement the same. We support our research with pilot production of the products.

We are also developing precious metal complexes, Catalysts, Legends etc.

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Synthesis with Catalysts Pvt Ltd.’s strength lies in its state-of- the-art infrastructure and R&D capabilities. Innovative process development is the foundation of SWC’s success. Our team of highly qualified R&D experts in process of research and technology development work 24 hours for inventing new processes and Optimizing product development capabilities. Our main focus is developing innovative processes, which could help our partners in reducing their costs and production time. Our Scientists constantly work for cost-effective ways of developing products, ensuring better service for our clients.

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Asymmetric Organocatalysis in Drug Development—Highlights of Recent Patent Literature

green chemistry, SYNTHESIS Comments Off

May 242018

Enantioselective organocatalytic reactions published in the recent patent literature are highlighted in this review and include inter- and intramolecular phase-transfer conjugate additions catalyzed by quaternized cinchona alkaloids, a Diels–Alder reaction catalyzed by oxazaborolidine complexes, asymmetric Betti reactions, the Lonza synthesis of l-carnitine, and several Corey–Bakshi–Shibata reductions.

Asymmetric Organocatalysis in Drug Development—Highlights of Recent Patent Literature

David L. Hughes*

Cidara Therapeutics, Inc., 6310 Nancy Ridge Drive, Suite 101, San Diego, California 92121, United States

Org. Process Res. Dev., 2018, 22 (5), pp 574–584

DOI: 10.1021/acs.oprd.8b00096

Publication Date (Web): April 19, 2018

*E-mail: dhughes@cidara.com.

https://pubs.acs.org/doi/10.1021/acs.oprd.8b00096

///////////////Asymmetric Organocatalysis

1,2 Diaminocyclohexane from Synthesis with Catalysts Pvt Ltd

ANTHONY CRASTO, MANUFACTURING, Presentations, PROCESS, SYNTHESIS, Uncategorized Comments Off

Apr 302018

+91- 999-997-2051

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Website

http://www.synthesiswithcatalysts.com/

bpk@synthesiswithcatalysts.com

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Founder at Synthesis with Catalysts Pvt. Ltd, axayrp@gmail.com

Basu Agarwal and Dr Razi Abdi

shr@synthesiswithcatalysts.com, ba@synthesiswithcatalysts.com

We are also developing precious metal complexes, Catalysts, Legends etc.

We are continuously working to reset standards of purity with our products.

We have a world class lab with all advance analytical testing machines.

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tert-butyl (N-[3-[(3S,4R)-3-amino-4-fluoro-4-(hydroxymethyl)tetrahydrofuran-3-yl]-4-fluorophenyl]acetamide)

ANTHONY CRASTO, spectroscopy, SYNTHESIS Comments Off

Apr 272018

tert-butyl (N-[3-[(3S,4R)-3-amino-4-fluoro-4-(hydroxymethyl)tetrahydrofuran-3-yl]-4-fluorophenyl]acetamide)

1H-NMR (500 MHz, DMSO-d6): 1.31 (s, 9H), 2.02 (s, 3H), 3.21 (m, 1H), 3.88 (m, 1H), 3.94 (m, 1H), 4.03 (m, 1H), 4.13 (m, 1H), 4.74 (m, 1H), 5.07 (m, 1H), 7.08 (m, 1H), 7.43 (bs, 1H), 7.63 (m, 1H), 7.67 (m, 1H), 10.03 (s, 1H) .

13C-NMR (125 MHz, DMSO-d6): 24.3, 28.5, 60.8, 65.1, 72.6, 78.1, 78.9, 105.8, 116.4, 119.7, 120.8, 127.2, 136.2, 155.2, 156.4, 168.7.

19F-NMR (470.6 MHz, DMSO-d6): -164.77, -117.26.

/////////////

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00069

Catalyst-free and solvent-free hydroboration of aldehydes

ANTHONY CRASTO, spectroscopy, SYNTHESIS Comments Off

Mar 302018

Green Chem., 2018, Advance Article
DOI: 10.1039/C8GC00042E, Communication

Hanna Stachowiak, Joanna Kazmierczak, Krzysztof Kucinski, Grzegorz Hreczycho
For the first time, a general method for catalyst-free and solvent-free hydroboration of various aldehydes has been developed

Catalyst-free and solvent-free hydroboration of aldehydes

Hanna Stachowiak,^a Joanna Kaźmierczak,^a Krzysztof Kuciński^a and Grzegorz Hreczycho*^a

Author affiliations

*Corresponding authors

^aFaculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61-614 Poznań, Poland
E-mail: g.h@amu.edu.pl

Abstract

A simple catalyst-free and solvent-free method for the hydroboration of various aldehydes bearing a wide array of electron-withdrawing and electron-donating groups was developed. Unlike aldehydes, the addition of boranes to ketones is less efficient and is thus advantageous for the chemoselective reduction of the former ones. It is suggested that the described transformation proceeds with the formation of Lewis acid–base adducts, which facilitates further hydroboration.

4,4,5,5-tetramethyl-2-((4-methylbenzyl)oxy)-1,3,2-dioxaborolane (3b) [1] 4,4,5,5-tetramethyl-2-((4-methylbenzyl)oxy)-1,3,2-dioxaborolane was obtained as colorless oil in 97% yield.

1H NMR (400 MHz, CDCl3) δ (ppm) = 1.29 (s, 12H), 2.36 (s, 3H), 4.91 (s, 2H), 7.17 (d, J = 7.9 Hz, 2H), 7.27-7.30 (m, 2H).

13C NMR (101 MHz, CDCl3) δ (ppm) = 21.3, 24.7, 66.7, 83.0, 127.0, 127.2, 129.1, 129.3, 136.4, 137.1.

11B NMR (128 MHz, CDCl3) δ (ppm) = 22.5.

EA: C14H21BO3 (248.16): calcd.C 67.77; H 8.53; found C 67.66; H 8.47.

11B NMR (128 MHz, CDCl3) δ (ppm) = 22.5.

////////////hydroboration

http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C8GC00042E?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Concise synthesis of ketoallyl sulfones through an iron-catalyzed sequential four-component assembly

green chemistry, spectroscopy, SYNTHESIS, Uncategorized Comments Off

Mar 092018

Concise synthesis of ketoallyl sulfones through an iron-catalyzed sequential four-component assembly

Green Chem., 2018, 20,973-977
DOI: 10.1039/C7GC03719H, Communication

Fuhong Xiao, Chao Liu, Dahan Wang, Huawen Huang, Guo-Jun Deng
A three starting material four component reaction (3SM-4CR) strategy is described to prepare [small beta]-acyl allylic sulfones from methyl ketones, sodium sulfinates and dimethylacetamide (DMA) in an iron-catalyzed oxidative system.

Concise synthesis of ketoallyl sulfones through an iron-catalyzed sequential four-component assembly

Fuhong Xiao,*^a Chao Liu,^a Dahan Wang,^a Huawen Huang^a and Guo-Jun Deng*^a

Author affiliations

* Corresponding authors

^a Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan 411105, China
E-mail: fhxiao@xtu.edu.cn, gjdeng@xtu.edu.cn

Abstract

A three starting material four component reaction (3SM-4CR) strategy is described to prepare β-acyl allylic sulfones from methyl ketones, sodium sulfinates and dimethylacetamide (DMA) in an iron-catalyzed oxidative system. In this process, DMA was used as a dual synthon to provide two carbons. A broad range of functional groups were tolerated in this reaction system.

1-phenyl-2-(tosylmethyl)prop-2-en-1-one (3ab)

43.2 mg, 72% yield).

1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2H), 7.68-7.65 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 6.25 (s, 1H), 6.02 (s, 1H), 4.35 (s, 2H), 2.39 (s, 3H).

13C NMR (100 MHz, CDCl3) δ 194.7, 144.9, 136.1, 135.8, 135.7, 133.9, 132.6, 129.8, 129.6, 128.3, 128.2, 57.7, 21.6.

HRMS calcd. for: C17H17O3S+ [M+H]+ 301.08929, found 301.08908

1H NMR PREDICT

13C NMR PREDICT ABOVE

////////

Cc1ccc(cc1)S(=O)(=O)CC(=C)C(=O)c2ccccc2

Fluoroalkylation reactions in aqueous media: a review

green chemistry, PROCESS, SYNTHESIS, Uncategorized Comments Off

Mar 062018

Fluoroalkylation reactions in aqueous media: a review

Green Chem., 2018, Advance Article
DOI: 10.1039/C8GC00078F, Tutorial Review

Hai-Xia Song, Qiu-Yan Han, Cheng-Long Zhao, Cheng-Pan Zhang
Recent advances in aqueous fluoroalkylation using various fluoroalkylation reagents are summarized in this review.

Fluoroalkylation reactions in aqueous media: a review

Hai-Xia Song,^a Qiu-Yan Han,^a Cheng-Long Zhao^a and Cheng-Pan Zhang*^a

Author affiliations

* Corresponding authors

^a School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, 430070, Wuhan, China
E-mail: zhangchengpan1982@hotmail.com, cpzhang@whut.edu.cn

Abstract

This review highlights the progress of aqueous fluoroalkylation over the past few decades. Fluorine-containing functionalities are important design elements in new pharmaceuticals, agrochemicals, and functional materials, due to their unique effects on the physical, chemical, and/or biological properties of a molecule. Because the environmental concerns are receiving increasing attention in organic synthesis, the development of methods for the mild, environment-friendly, and efficient incorporation of fluorinated or fluoroalkylated groups into the target molecules is of broad interest. At the early stage, most of the fluoroalkylation reactions and their variants were thought in principle to be hydrophobic. Recently, the environment-benign fluoroalkylation reactions by taming nucleophilic, radical, or electrophilic fluoroalkylation reagents in water or in the presence of water have been explored, building a new prospect for green chemistry. The use of significant catalytic systems and/or the newly developed reagents is the key to the success of these reactions. Water is used as a (co)solvent and/or a reactant in aqueous fluoroalkylation, including trifluoromethylation, difluoromethylation, monofluoromethylation, trifluoroethylation, perfluoroalkylation, trifluoromethylthiolation, and other conversions, under environment-friendly conditions. Although great accomplishments have been achieved, they are just the tip of the iceberg with a wide scope for improvement. This review will draw great attention and inspire more contributions in the development of new aqueous fluoroalkylation reactions

Conclusion

In conclusion, aqueous fluoroalkylation including trifluoromethylation, difluoromethylation, monofluoromethylation, trifluoroethylation, perfluoroalkylation, trifluoromethylthiolation, and difluoromethylthiolation are summarized in this review.

The successful assembly of nucleophilic, radical, and/or electrophilic fluoroalkylation reagents and water in fluoroalkylation reactions opens a new prospect for green chemistry. The valid catalytic systems and the newly developed reagents contribute greatly for the success of the aqueous fluoroalkylation. As a provisional conclusion, the shelf-stable electrophic and radical fluoroalkylation reagents such as “+CF3”, “+CF2H”, “ +CH2CF3”, RfnSO2M (M = Na, 1/2Zn, Cl), RfnX (X = I, Br), and “+ SCF3” reagents are basically compatible with water or aqueous media, which enable a variety of aqueous fluoroalkylation reactions under mild conditions. In the case of nucleophilic fluoroalkylation reagents that are moisture-sensitive (e.g., “−CF3” and “− SCF3” sources), the choice of an appreciate transition-metal partner to stabilize the fluorinated anions is crucial to promote the reaction.

By coupling with the right transition metals, these sensitive fluoroalkylation reagents or intermediates would have sufficient lifetimes to finish the target conversions. Water is abundant and environmentally benign, and it has advantages such as high dielectric constant, large cohesive energy density, and strong hydrogen bonding interaction, which desirably influence the efficiency and selectivity of chemical reactions. In this reviw, water works as a (co)solvent and/or a reactant to facilitate the fluoroalkylation by increasing the dissolving of the reaction participants, providing a proton donor, or behaving as a O-nucleophile.

The fluoroalkylation reactions performed in aqueous media are mild, easily controlled, and environmental friendly, which fit well the principles of green chemistry. Although breakthroughs have been made, siginificant improvement is still neccessary for a wide range of fluoroalkylation reactions. A tough question is whether the direct trifluoromethoxylation can be performed in aqueous conditions, despite the reaction of excess AgOCF3 with α-diazo esters surviving in CH3CN in the presence of residue moisture or a trace amount of D2O (Scheme 120).155 The ionic [Me4N][SCF3] and [Me4N][SeCF3] salts, and their variants containing free − SCF3 or − SeCF3 anions, also encounter similar problems, even through trace of water proved to be essential for the functionalization of α-diazo carbonyls.156,157 The sensitive −XCF3 (X = O, S, Se) anions tend to undergo α-fluorine elimination to generate fluoride ( − F) and carbonic difluoride (CXF2), and the presence of water is generally believed to accelerate this transformation, leading to rapid decomposition of these reagents.

We hope that this review will attract more interests and contributions in the development of aqueous fluoroalkylation with these extraordinary reagents. Aqueous fluoroalkylation methods have changed the way to synthesize fluorinated molecules in terms of the biological and physicochemical properties. Since the aspects of green chemistry have drawn much attention from society, the pursuit of more efficient and milder reaction conditions for greener fluoroalkylation in aqueous media will never be terminated. We hope that this review will serve as a guide to understand and as an appeal to engage in the field of green fluorine chemistry.

To meet the principles of green chemistry, the development of new fluoroalkylation reagents and efficient catalytic systems will be continuously vital for the mild and environment-benign fluoroalkylation. It is anticipated that a growing number of green fluoroalkylation methodologies in aqueous media will arise in the near future.

Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents

drugs, spectroscopy, SYNTHESIS Comments Off

Feb 082018

Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents

Med. Chem. Commun., 2018, Advance Article
DOI: 10.1039/C7MD00551B, Research Article

Yi-Bin Li, Wen Hou, Hui Lin, Ping-Hua Sun, Jing Lin, Wei-Min Chen
Two series of 5-hydroxy-2-methyl-4H-pyran-4-one derivatives were synthesized and their antiglioma activities were evaluated.

Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents

Yi-Bin Li,^a Wen Hou,^a Hui Lin,^a Ping-Hua Sun,^a Jing Lin*^a and Wei-Min Chen*^a

Author affiliations

* Corresponding authors

^a College of Pharmacy, Jinan University, Guangzhou 510632, P. R. China
E-mail: linjing_jnu@163.com, twmchen@jnu.edu.cn
Fax: +86 20 8522 4766
Tel: +86 20 8522 1367

Abstract

D-2-Hydroxyglutarate (D-2HG) is frequently found in human brain cancers. Approximately 50–80% of grade II glioma patients have a high level of D-2HG production, which can lead to cancer initiation. In this study, a series of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives were designed and synthesized as antiglioma agents, and their related structure–activity relationships are discussed. Among these novel compounds, 4a exhibited promising anti-proliferative activity against glioma HT1080 cells and U87 cells with an IC₅₀ of 1.43 μM and 4.6 μM, respectively. Further studies found that the most active compound (4a) shows an 86.3% inhibitory rate against the intracellular production of D-2HG at 1 μM, and dramatic inhibitory effects, even at 1 μM on the colony formation and migration of U87 and HT1080 cells.

6,6′-((4-(Benzyloxy)phenyl)methylene)bis(5-hydroxy-2-methyl-4H-pyran-4- one) (4a) The reaction was performed according to the general procedure C, using 1 (1.00 g, 7.90 mmol) and 4-(benzyloxy)benzaldehyde (0.84 g, 3.95 mmol).2 The crude product was recrystallized from isopropanol affording a white powder 4a (1.53 g, 87%): mp 261.4-262.1oC; 1HNMR (300 MHz, DMSO-d6)  2.22 (s, 6H, CH3), 5.08 (s, 3H, OCH2- Ph), 5.96 (s, 1H, CH-Ar), 6.25 (s, 2H, C=CH), , 7.01 (d, J = 9.0 Hz, 2H, Ar-H3’/H5’), 7.22 (d, J = 9.0 Hz, 2H, Ar-H2’/H6’), 7.31-7.45 (m, 5H, Ph-H); 13CNMR (75 MHz, DMSO-d6)  173.95, 165.08, 158.12, 151.20, 147.68, 142.19, 140.77, 137.42, 129.87, 128.91, 128.16, 127.69, 115.46, 114.97, 111.74, 69.69, 19.63; ESI-MS m/z: 447.1 [M+H]+ ; ESI-HRMS m/z: 447.1438 [M+H]+ , calcd for C26H23O7 447.1438.

///////////http://pubs.rsc.org/en/Content/ArticleLanding/2018/MD/C7MD00551B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FMD+%28RSC+-+Med.+Chem.+Commun.+latest+articles%29#!divAbstract

Unconventional Method for the Synthesis of 3-Carboxyethyl-4-formyl(hydroxy)-5-arylpyrazoles

spectroscopy, SYNTHESIS, Uncategorized Comments Off

Feb 082018

Unconventional Method for Synthesis of 3-Carboxyethyl-4-formyl(hydroxy)-5-aryl-N-arylpyrazoles

Michael J. V. da Silva^†, Julia Poletto^†, Andrey P. Jacomini^†, Karlos E. Pianoski^†, Davana S. Gonçalves^†, Gessica M. Ribeiro^†, Samara M. de S. Melo^†, Davi F. Back^‡, Sidnei Moura^§, and Fernanda A. Rosa^*^†

^† Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil

^‡ Departamento de Química, Universidade Federal de Santa Maria (UFSM), 97110-970 Santa Maria, RS, Brazil

^§ Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), 295070-560 Caxias do Sul, RS, Brazil

J. Org. Chem., 2017, 82 (23), pp 12590–12602

DOI: 10.1021/acs.joc.7b02361

Publication Date (Web): November 2, 2017

*E-mail: farosa@uem.br

Cite this:J. Org. Chem. 82, 23, 12590-12602

Abstract

An alternative highly regioselective synthetic method for the preparation of 3,5-disubstituted 4-formyl-N-arylpyrazoles in a one-pot procedure is reported. The methodology developed was based on the regiochemical control of the cyclocondensation reaction of β-enamino diketones with arylhydrazines.

Structural modifications in the β-enamino diketone system allied to the Lewis acid carbonyl activator BF₃ were strategically employed for this control. Also a one-pot method for the preparation of 3,5-disubstituted 4-hydroxymethyl-N-arylpyrazole derivatives from the β-enamino diketone and arylhydrazine substrates is described.

J. Org. Chem. 2017, 82, 12590

4-Formyl-N-arylpyrazole substrates occupy a prominent position in the field of organic synthesis since they are key intermediates in obtaining a wide range of biologically active compounds. Because of the synthetic versatility of the 4-formyl-N-arylpyrazole skeleton, their synthesis has been extensively explored. In an extension of their previously published research,

Rosa and co-workers at Universidade Estadual de Maringá described a one-pot synthetic method that regioselectively produced 3,5-disubstituted-4-formyl-N-arylpyrazoles . The β-enamino diketone starting materials were readily synthesized via published procedures. High regioselectivity was secured via the use of BF₃·OEt₂ as the carbonyl activator and a bulky amine as the enamine component. Acetonitrile proved to be the most suitable solvent for the reaction.

After an aqueous workup, the desired pyrazoles were obtained in excellent yields. A variety of functional groups were tolerated on the two aryl substituents. This operationally simple procedure afforded the 4-formyl-N-arylpyrazoles in high yields, regioselectively. Furthermore, the formyl group could be reduced in situ with sodium borohydride to generate the corresponding 4-hydroxymethyl-N-arylpyrazoles.

3-(Ethoxycarbonyl)-4-formyl-5-(4-nitrophenyl)-1-phenyl-1H-pyrazole (3a)

Light yellow solid; yield: 0.150 g (82%); mp 147.0–149.2 °C;

¹H NMR (300.06 MHz, CDCl₃) δ (ppm) 1.47 (t, 3H, J = 7.1 Hz, O–CH₂–CH₃), 4.54 (q, 2H, J = 7.1 Hz, O–CH₂-CH₃), 7.19–7.25 (m, 2H, Ph), 7.32–7.43 (m, 3H, Ph), 7.48 (d, 2H, J = 8.9 Hz, 4-NO₂C₆H₄), 8.19 (d, 2H, J = 8.9 Hz, 4-NO₂C₆H₄), 10.57 (s, 1H, CHO);

¹³C NMR (75.46 MHz, CDCl₃) δ (ppm) 14.4 (O–CH₂–CH₃), 62.3 (O-CH₂–CH₃), 122.0 (C4), 123.5 (4-NO₂C₆H₄), 125.9 (Ph), 129.5 (Ph), 129.6 (Ph), 131.8 (4-NO₂C₆H₄), 134.1 (4-NO₂C₆H₄), 137.8 (Ph), 143.5 (C5), 145.0 (C3), 148.4 (4-NO₂C₆H₄), 161.5 (COOEt), 186.6 (CHO);

HRMS (ESI+): calcd for C₁₉H₁₆N₃O₅⁺, [M+H]⁺: 366.1084, found 366.1101.

//////////////https://pubs.acs.org/doi/abs/10.1021/acs.joc.7b02361