Novel Drug Approvals for 2017, A Review/Compilation « New Drug Approvals

Novel Drug Approvals for 2017, A Review/Compilation « New Drug Approvals

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.

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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.

 

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(Z and E)-4-(Methylamino)-3-(4-nitrobenzoyl)-2-oxobut-3-enoic Acid Ethyl Ester

  

(Z and E)-4-(Methylamino)-3-(4-nitrobenzoyl)-2-oxobut-3-enoic Acid Ethyl Ester (2a)

Light yellow solid; yield: 0.276 g (90%); Z/E ratio in CDCl₃: 80/20; mp 143.8–145.3 °C;

 

 ¹H NMR (300.06 MHz, CDCl₃) δ (ppm) (Z) 1.29 (t, 3H, J = 7.2 Hz, O–CH₂–CH₃), 3.24 (dd, 3H, J = 5.2, 0.7 Hz, NH-CH₃), 4.17 (q, 2H, J = 7.2 Hz, O–CH₂-CH₃), 7.64 (dd, 1H, J = 14.1, 0.7 Hz, H4), 7.75 (d, 2H, J = 8.8 Hz, 4-NO₂C₆H₄), 8.28 (d, 2H, J = 8.9 Hz, 4-NO₂C₆H₄), 10.67 (bs, 1H, NH); (E) 1.14 (t, 3H, J = 7.2 Hz, O–CH₂–CH₃), 3.34 (dd, 3H, J = 5.2, 0.8 Hz, NH-CH₃), 3.81 (q, 2H, J = 7.2 Hz, O–CH₂-CH₃), 7.62 (d, 2H, J = 8.8 Hz, 4-NO₂C₆H₄), 8.20 (dd, 1H, J = 14.3, 0.8 Hz, H4), 8.23 (d, 2H, J= 8.8 Hz, 4-NO₂C₆H₄), 10.79 (bs, 1H, NH);

 

 ¹³C NMR (75.46 MHz, CDCl₃) δ (ppm) (Z) 13.9 (O–CH₂–CH₃), 37.2 (NH-CH₃), 61.8 (O-CH₂–CH₃), 107.0 (C3), 123.7, 129.5, 144.5, 149.2 (4-NO₂C₆H₄), 163.1 (C4), 164.9 (COOEt), 186.9 (C2), 190.8 (C3′); (E) 13.7 (O–CH₂–CH₃), 37.1 (NH-CH₃), 62.0 (O-CH₂–CH₃), 106.7 (C3), 123.4, 128.6, 146.4, 148.8 (4-NO₂C₆H₄), 163.3 (C4), 164.4 (COOEt), 183.3 (C2), 193.7 (C3′);

 

HRMS (ESI+): calcd for C₁₄H₁₅N₂O₆⁺, [M+H]⁺: 307.0925, found 307.0938.

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

DOI: 10.1021/acs.joc.7b02361

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