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Friday, 9 March 2018

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

 
Author affiliations

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
 
STR1 STR2

1H NMR PREDICT




13C NMR PREDICT ABOVE

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

Thursday, 15 February 2018

p-Aminophenol

STR1 STR2
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, 7.4 spectrum for 4-Aminophenol

1D 1H ABOVE


2D [1H,1H]-TOCSY, 7.4 spectrum for 4-Aminophenol

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

1D 13C, 7.4 spectrum for 4-Aminophenol

1D 13C ABOVE


1D DEPT90, 7.4 spectrum for 4-Aminophenol

1D DEPT90 ABOVE

1D DEPT135, 7.4 spectrum for 4-Aminophenol

1D DEPT135 ABOVE

2D [1H,13C]-HSQC, 7.4 spectrum for 4-Aminophenol

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

2D [1H,13C]-HMBC, 7.4 spectrum for 4-Aminophenol

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

Thursday, 8 February 2018

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

 
Author affiliations

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.

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

Abstract Image

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

 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.201782 (23), pp 12590–12602
DOI: 10.1021/acs.joc.7b02361
Publication Date (Web): November 2, 2017
 
*E-mail: farosa@uem.br

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.

 

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.
 
STR1 STR2
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–CH2CH3), 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.
 

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

STR1 STR2 str3
(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–CH2CH3), 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–CH2CH3), 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.201782 (23), pp 12590–12602
DOI: 10.1021/acs.joc.7b02361

Wednesday, 31 January 2018

(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

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.

Abstract

Abstract Image
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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