1-(4-Cyanophenyl)piperazine

1-(4-Cyanophenyl)piperazine

1-(4-Cyanophenyl)piperazine (1a).1 Isolated as a mixture of mono (1a) and di (3) arylated products ~9:1. Conversion: quantitative. Peaks attributed to 1a: 1H NMR (400 MHz, CD3Cl) δH 7.47 (m, 2H, arH), 6.83 (m, 2H, ar-H), 3.26 (m, 4H, pip-H), 2.99 (m, 4H, pip-H), 1.69 (br s, 1H, NH). Peaks attributed to 3: 7.52 (d, J = 9.0 Hz, 4H, ar-H), 6.88 (d, J = 9.0 Hz, 4H, ar-H), 3.29 (s, 8H, pip-H).

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00090

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https://pubs.acs.org/doi/suppl/10.1021/acs.oprd.8b00090/suppl_file/op8b00090_si_001.pdf

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

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.

 

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Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00069

BRUSH UP YOUR NMR, 4-(3,5-Dichloropyridin-4-yl)morpholine

3,5-Dichloro-4-morpholinopyridine

Preparation of 4-(3,5-Dichloropyridin-4-yl)morpholine (5).(Pichowicz, M.; Crumpler, S.; McDonald, E.; Blagg, J. Tetrahedron 2010, 66, 2398, DOI: 10.1016/j.tet.2010.01.101)

 

 5 as a light-orange solid.

 

1H NMR (CDCl3, 400 MHz): δ = 8.35 (2H, s), 3.84 (4H, m), 3.37 (4H, m);

 

13C NMR (CDCl3, 101 MHz): δ = 150.8, 149.3, 128.4, 67.4, 50.4;

 

HRMS–ESI+: m/z [M + H]+ calcd for C9H11Cl2N2O+: 233.02429; found: 233.02446.

 

 

 

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00009

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Clc2cncc(Cl)c2N1CCOCC1

This paper demonstrates an efficient, mild, and chemoselective synthesis of various thioesters via a HOTf-catalyzed S-acetylation of aromatic and aliphatic thiols using isopropenyl acetate as a cheap and convenient acetylating agent. During our tests, we also investigated the differences between the activities of metal triflates and triflic acid as catalysts in the acetylation of thiols. Finally, the potential of our concept has been increased by the implementation of Nafion as a heterogeneous catalyst for S-acetylation of thiols.

S-Acetylation of Thiols Mediated by Triflic Acid: A Novel Route to Thioesters

Krzysztof Kuciński*  and Grzegorz Hreczycho* 

Faculty of Chemistry, Adam Mickiewicz University in Poznań, ul. Umultowska 89b, 61-614 Poznań, Poland

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00378

Publication Date (Web): March 12, 2018

Copyright © 2018 American Chemical Society

*E-mail: kucinski.k@amu.edu.pl., *E-mail: g.h@amu.edu.pl. Web: http://ghgroup.home.amu.edu.pl.

 

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

 

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

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

p-Aminophenol

 

p-Aminophenol [123-30-8].

M.p. 182 °C; 1H NMR (300 MHz, d6-DMSO): 4.37 (br s, 2H, NH2), 6.37-6.44 (m, 2HAr), 6.44-6.50 (m, 2HAr), 8.33 (br s, 1H, OH);

13C NMR (75 MHz, d6-DMSO): δ 115.2 (2 CHAr), 115.5 (2 CHAr), 140.7 (Cq Ar), 148.2 (Cq Ar);

IR (ATR) max: 3338, 3279, 1471; MS (ESI+ ): 110.1 ([M+H]+ , 100).

1D 1H ABOVE

2D [1H,1H]-TOCSY ABOVE

1D 13C ABOVE

1D DEPT90 ABOVE

1D DEPT135 ABOVE

2D [1H,13C]-HSQC ABOVE

2D [1H,13C]-HMBC ABOVE

A sustainable procedure toward alkyl arylacetates: palladium-catalysed direct carbonylation of benzyl alcohols in organic carbonates

A sustainable procedure toward alkyl arylacetates: palladium-catalysed direct carbonylation of benzyl alcohols in organic carbonates

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC03619A, Communication

Yahui Li, Zechao Wang, Xiao-Feng Wu
A sustainable procedure for the synthesis of various alkyl arylacetates from benzyl alcohols has been developed

 

A sustainable procedure toward alkyl arylacetates: palladium-catalysed direct carbonylation of benzyl alcohols in organic carbonates

 

Yahui Li,^a  Zechao Wang^a  and  Xiao-Feng Wu*^ab 

Author affiliations

* Corresponding authors

^a Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany

^b Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People's Republic of China
E-mail: Xiao-Feng.Wu@catalysis.de

Abstract

A sustainable procedure for the synthesis of various alkyl arylacetates from benzyl alcohols has been developed. With palladium as the catalyst and organic carbonates as the green solvent and in situ activator, benzyl alcohols were carbonylated in an efficient manner without any halogen additives.

Ethyl 2-phenylacetate
1H NMR (300 MHz, Chloroform-d) δ 7.32 – 7.08 (m, 5H), 4.08 (q, J = 7.1 Hz, 2H), 3.54 (s, 2H), 1.18 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 171.61, 134.17, 129.24, 128.54, 127.03, 60.85, 41.45, 14.18.

//////http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C7GC03619A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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

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

(2R,4R)-Methyl-2-tert-butyl-1,3-thiazolidine-3-formyl-4-carboxylate

(2R,4R)-Methyl-2-tert-butyl-1,3-thiazolidine-3-formyl-4-carboxylate (18)

the resulting crude was purified by flash chromatography on silica gel (eluted by 30–50% ethyl acetate in hexane). The collected fractions were evaporated and recrystallized from diethyl ether–hexanes (1:1, v/v) to afford N-formyl thazolidine 18 (300 g, 90% yield, 97% HPLC purity) as colorless crystals.

 

1H NMR (400 MHz, CDCl3, mixture of conformers (7:1), major): δ 8.35 (s, 1H), 4.89 (t, J = 8.0 Hz, 1H), 4.74 (s, 1H), 3.77 (s, 3H), 3.34–3.24 (m, 2H), 1.03 (s, 9H) ppm.

 

13C NMR (100 MHz, CDCl3, mixture of conformers (7:1), major): δ 170.1, 162.8, 75.3, 61.6, 52.8, 38.7, 33.0, 26.5 ppm. HRMS (ESI) m/z calcd for C10H17NO3S (M+H)+ 232.1002, found 232.1001.

 

Process Development and Scale-up Total Synthesis of Largazole, a Potent Class I Histone Deacetylase Inhibitor

Qi-Yin Chen†‡§, Pravin R. Chaturvedi§, and Hendrik Luesch*†‡§ 

†Department of Medicinal Chemistry and ‡Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States

§ Oceanyx Pharmaceuticals, Inc., Sid Martin Biotechnology Incubator, 12085 Research Drive, Alachua, Florida 32615, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00352

 

*E-Mail: luesch@cop.ufl.edu; Tel.: +1-352-273-7738; Fax: +1-352-273-7741.

http://pubs.acs.org/doi/10.1021/acs.oprd.7b00352

Abstract

Herein we describe the research and development of the process for the scale-up total synthesis of largazole, a potent class I selective histone deacetylase (HDAC) inhibitor, a potential anticancer agent and also useful for the treatment of other disorders where transcriptional reprogramming might be beneficial. The synthetic route and conditions for each fragment and final product were modified and optimized to make them suitable for larger-scale synthesis. With the process we developed, hundreds of grams of each fragment and decagrams of final product largazole were synthesized in good to excellent yields. The final target largazole was obtained in 21% overall yield over eight steps based on the longest sequence with over 95% HPLC purity.

 

 

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