Metal-free synthesis of polysubstituted pyrroles using surfactants in aqueous medium

Metal-free synthesis of polysubstituted pyrroles using surfactants in aqueous medium

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01874F, Communication

Amrendra Kumar, Ramanand, Narender Tadigoppula
An efficient and metal-free method has been developed for the synthesis of polysubstituted pyrrole derivatives with combination of sodium dodecyl sulphate (SDS) and Triton X-100 surfactants using water as a solvent at room temperature in 2-6 h and under microwave conditions (10 min) with good to excellent yields.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC01874F?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Metal-free synthesis of polysubstituted pyrroles using surfactants in aqueous medium

 

Amrendra Kumar,^a  Ramanand^a  and  Narender Tadigoppula*^a 

*Corresponding authors

^aMedicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow-226 031, India
E-mail: t_narendra@cdri.res.in
Tel: +91-522-2772450 Ext: 4737

Dr. Narender Tadigoppula

Principal Scientist
Medicinal & Process Chemistry
Central Drug Research Institute
India

Dr. Narender Tadigoppula is currently principal scientist in the department of medicine chemistry central drug research institute. He published more than 30 research articles. His major major research activities are identification of biologically active lead molecules through activity guided fraction and isolation work on the medicinal plants, marine organisms and microorganisms for metabolic diseases (hyperglycemia, dyslipidemia), parasitic diseases (leishmania and malaria), cancer etc., and chemical transformation of natural products of biological importance to improve their potency. We synthesize these biologically active lead molecules and their analogues in our laboratory. We have identified several lead molecules from the Indian medicinal plants for various disease areas as described below and further work is in progress to develop natural products based drugs.

Abstract

An efficient and metal-free method has been developed for the synthesis of polysubstituted pyrrole derivatives via intermolecular cycloaddition of substituted 1-phenyl-2-(phenylamino)-ethan-1-one/1-phenyl-2-(phenylamino)-propan-1-ones/2-((4-methoxyphenyl)amino)-1-(thiophen-2-yl)ethan-1-one/1-(furan-2-yl)-2-((4-methoxyphenyl)amino)ethan-1-one/1-(benzofuran-3-yl)-2-((4-methoxyphenyl)amino)ethan-1-one and dialkyl acetylene dicarboxylate/ethylbutynoate in the presence of a combination of sodium dodecyl sulphate (SDS) and Triton X-100 surfactants using water as a solvent at room temperature in 2–6 h under microwave conditions (10 min) with good to excellent yields.

Diethyl-1-(4-methoxyphenyl)-4-(p-tolyl)-1H-pyrrole 2,3dicarboxylate

white solid, yield 77%, mp 128-130 ;
1H NMR (400 MHz, CDCl3) δ 7.38(d, J = 8.2,2H), 7.31 (d, J = 7.9, 2H), 7.21 (d, J = 7.12, 2H), 6.99-6.96 (m, 3H), 4.31 (q, J = 7.2 Hz, 2H), 4.12 (q, J = 7.6Hz, 2H), 3.88 (s, 3H), 2.38 (s, 3H), 1.31 (t, J = 7.9Hz, 3H), 1.19 (t, J = 7.5Hz, 3H) ;
13C NMR (100 MHz, CDCl3) δ 166.3, 159.9, 149.0, 148.8, 136.7, 132.6, 130.3, 129.2, 127.6, 125.8, 124.5, 123.4, 121.5, 118.3, 110.5, 110.2, 61.2, 60.7, 56.0, 21.1, 14.0, 13.9.
IR (KBr) ṽ (cm-1): 2981.9, 1717.9, 1514.1, 1419.2, 1381.3, 1245.0, 1175.9, 1226.7, 1043.6, 835.7, 755.3, 663.
HRESIMS: m/zcalcd for [M+H]+ C24H26NO5 408.1805 found 408.1845.
 

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O=C(OCC)c2c(c(cn2c1ccc(OC)cc1)c3ccc(C)cc3)C(=O)OCC

tert-Butyl 4-(2,3-diaminophenyl)piperazine-1- carboxylate

tert-Butyl 4-(2,3-diaminophenyl)piperazine-1- carboxylate (4)

1H NMR (400 MHz, CDCl3), δ in ppm = 6.68 (t, 1H), 6.59 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 7.6 Hz, 1H), 3.56 (br s, 8H), 2.83 (s, 4H), 1.49 (s, 9H). This is consistent with literature data.1

Small molecule piperazinyl-benzimidazole antagonists of the gonadotropin-releasing hormone (GnRH) receptor

 

Richard Fjellaksel,*abc  Marc Boomgaren,c  Rune Sundset,ad  Ira H. Haraldsen,e  Jørn H. Hansenc  and Patrick J. Rissefg 

 Author affiliations

*Corresponding authors

aMedical Imaging Group, Department of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
E-mail: richard.fjellaksel@uit.no

bDrug Transport and Delivery Group, Department of Pharmacy, UiT The Arctic University of Norway, 9037 Tromsø, Norway

cOrganic Chemistry Group, Department of Chemistry, UiT The Arctic University of Norway, 9037 Tromsø, Norway

dPET imaging center, division of diagnostics, UNN – University Hospital of North-Norway, 9038 Tromsø, Norway

eDepartment of neuropsychiatry and psychosomatic medicine, Oslo University Hospital, Oslo, Norway

fRealomics SFI, Department of Chemistry, University of Oslo, PO BOX 1033, Oslo 0371, Norway

gNorsk Medisinsk Syklotronsenter AS, Postboks 4950 Nydalen, 0424 Oslo, Norway

Abstract

In this communication, we report the synthesis and characterization of a library of small molecule antagonists of the human gonadotropin releasing hormone receptor based upon the 2-(4-tert-butylphenyl)-4-piperazinyl-benzimidazole scaffold via Cu-catalysed azide alkyne cycloaddition. Our main purpose was to find a more soluble compound based on the WAY207024 lead with nanomolar potency to inhibit the GnRH receptor. A late stage diversification by the use of click chemistry was, furthermore developed to allow for expansion of the library in future optimisations. All compounds were tested in a functional assay to determine the individual potency of inhibiting stimulation of the receptor by the endogenous agonist GnRH. In conclusion, we found that compound 8ashowed improved solubility compared to WAY207024 and nanomolar affinity to GnRH receptor.

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References 1. Pelletier, J. C.; Chengalvala, M.; Cottom, J.; Feingold, I.; Garrick, L.; Green, D.; Hauze, D.; Huselton, C.; Jetter, J.; Kao, W.; Kopf, G. S.; Lundquist, J. T. t.; Mann, C.; Mehlmann, J.; Rogers, J.; Shanno, L.; Wrobel, J., 2-phenyl-4-piperazinylbenzimidazoles: orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor. Bioorganic & medicinal chemistry 2008, 16 (13), 6617-40.

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Org. Chem. Front., 2018, Advance Article
DOI: 10.1039/C7QO00749C, Research Article

Qiangqiang Jiang, Xinghui Qi, Chenyang Zhang, Xuan Ji, Jin Li, Renhua Liu

An efficient method for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles has been developed through palladium(0) catalyzed dehydrogenative cyclization of N-arylidenearoylhydrazides without oxidants and hydrogen acceptors.

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Qiangqiang Jiang,a  Xinghui Qi,a  Chenyang Zhang,a  Xuan Ji,a  Jin Li*b  and  Renhua Liu*a 

*Corresponding authors

aSchool of Pharmacy, East China University of Science and Technology, Meilong Road 130, Shanghai 200237, China
E-mail: liurh@ecust.edu.cn

bChina Catalyst Holding Co., Ltd, Jingjiu Road 3, Chemical Park, Songmu Island, Puwan New District, Dalian 116699, China
E-mail: lijin@china-catalyst.com

Abstract

An efficient method for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles has been developed through palladium(0) catalyzed dehydrogenative cyclization of N-arylidenearoylhydrazides. By using this method, a wide range of functionalized and potentially biologically relevant 1,3,4-oxadiazole-containing compounds have been accessed in moderate to high isolated yields. The dehydrogenative cyclization process is characterized by the nonuse of any sacrificing hydrogen acceptors or oxidants and hydrogen gas as the only by-product, and therefore circumvents the recurring problems of over-oxidation and the compatibility with easily oxidizable functionalities in oxidation protocols.

109.6 mg, 87 % yield; White solid,

1H NMR (400 MHz, CDCl3) δ 8.13 – 8.08 (m, 2H), 8.06 (d, J = 8.7 Hz, 2H), 7.52 (m, 3H), 7.01 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H);

13C NMR (100 MHz, CDCl3) δ 164.51, 164.10, 162.33, 131.54, 129.03, 128.67, 126.80, 124.05, 116.38, 114.50, 55.46; M.p. 145-146 oC.

2-(4-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole12

1H NMR CDCL3

http://pubs.rsc.org/en/Content/ArticleLanding/2018/QO/C7QO00749C#!divAbstract

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Learn spectroscopy, Valeric acid or pentanoic acid. PROBLEM 1

.



HE IS EXCITED TOO



Product Name: Valeric acid


CAS:109-52-4




valeric acid

pentansäure

acide pentanoic

ペンタン酸

109-52-4 CAS

C5H10O2














Valeric acid, or pentanoic acid.


This 13C spectrum exhibits resonances at the following chemical shifts, and with the multiplicities indicated:


Shift (ppm)

Mult.

180.8

S

33.8

T

26.8

T

22.4

T

3.58

Q

(C5H10O2)



A= 13.4

B=22.4

C=26.8

D=33.8

E=180.6














1H NMR BELOW


t=0.78

m=1.22

m=1.46

t=2.2

s=11.8

















NMR IS EASY

EVEN MOM CAN TEACH YOU







2D [1H,1H]-TOCSY

Concentration: 100 mM

temperature: 298 K

pH: 7.4









1D DEPT90

Concentration: 100 mM

temperature: 298 K

pH: 7.4















1D DEPT135

Concentration: 100 mM

temperature: 298 K

pH: 7.4







2D [1H,13C]-HSQC

Concentration: 100 mM

temperature: 298 K

pH: 7.4










2D [1H,13C]-HMBC

Concentration: 100 mM

temperature: 298 K

pH: 7.4

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An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite

1-benzyl-2, 4, 5-triphenyl-1H-imidazole

  

. 1-Benzyl-2,4,5-triphenyl-1H-imidazole (5a, n = 1).

Off-white solid; m.p.: 160–162 °C;

anal. calcd. for C28H22N2: C, 87.01, H, 5.74, N, 7.25%. Found: C, 87.13, H, 5.70, N, 7.19%;

UV (λmax, ethanol) = 280 nm;

FT-IR (KBr, cm−1 ): 3060 (C–H stretch), 3031, 1600 (CN), 1497, 1483, 1447 (CC), 1352 (C–N stretch), 769, 697 (C–H band);

1 H NMR (400 MHz, DMSO): 5.16 (s, 2H, CH2), 6.74–7.67 (m, 20H, Ar–H) ppm;

13C NMR (100 MHz, DMSO): 47.6 (CH2, C8), 125.1 (CHarom, C28), 126.0 (CHarom, C26), 126.2 (CHarom, C30), 126.4 (CHarom, C11), 127.0 (CHarom, C15), 127.1 (CHarom, C16), 127.7 (CHarom, C20), 128.0 (CHarom, C21), 128.1 (CHarom, C25), 128.4 (CHarom, C13), 128.5 (CHarom, C18), 128.6 (CHarom, C27), 128.8 (C1), 128.8 (CHarom, C12), 128.9 (CHarom, C14), 130.1 (CHarom, C17), 130.3 (CHarom, C19), 130.5 (CHarom, C22), 130.7 (CHarom, C24), 131.0 (CHarom, C29), 134.4 (CHarom, C9), 135.1 (CHarom, C23), 136.8 (CHarom, C7), 137.0 (CHarom, C10), 137.2 (CHarom, C6), 145.4 (C2), 147.0 (C4) ppm;

MS: m/z = 387.5 (M + H)+

An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite

Jenifer J. Gabla,^a  Sunil R. Mistry^b  and  Kalpana C. Maheria*^a 

Jenifer J Gabla

S V National Institute of Technology, India
Jenifer J Gabla has obtained her MSc degree in Organic Chemistry, in the year 2013 from Uka Tarsadia University, Bardoli, Gujarat. She is currently pursuing her PhD in the area of solid acid catalyzed multicomponent reactions for the synthesis of biologically active drug molecules, at Applied Chemistry Department (ACD), S. V. National Institute of Technology (SVNIT) under the guidance of Kalpana Maheria, Assistant Professor & Head, ACD, SVNIT, Surat, Gujarat, India. Her research focuses on development of novel zeolite based catalytic materials and exploring their utility in the green process development for the synthesis of medicinal compounds. She has presented her research in several national and international conferences.

Kalpana C. Maheria

*Corresponding authors

^aApplied Chemistry Department, S. V. National Institute of Technology, Ichchhanath, Surat – 395007, India
E-mail:kcmaheria@gmail.com

^bMandvi Science College, Mandvi – 394160, Surat, India

Abstract

In the present study, the catalytic activity of various medium (H-ZSM-5) and large pore (H-BEA, H-Y, H-MOR) zeolites were studied as solid acid catalysts. The zeolite H-BEA is found to be an efficient catalyst for the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles through one-pot, 4-component reaction (4-CR) between benzil, NH₄OAc, substituted aromatic aldehydes and benzyl amine. The hydrophobicity, Si/Al ratio and acidic properties of zeolite BEA were well improved by controlled dealumination. The synthesized materials were characterized by various characterization techniques such as XRD, ICP-OES, BET, NH₃-TPD, FT-IR, pyridine FT-IR, ²⁷Al and ¹H MAS NMR. It has been observed that the dealumination of the parent zeolite H-BEA (12) results in the enhanced strength of Brønsted acidity up to a certain Si/Al ratio which is attributed to the inductive effect of Lewis acidic EFAl species, leading to the higher activity of the zeolite BEA (15) catalyst towards the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles under thermal solvent-free conditions with good to excellent yields. Using the present catalytic synthetic protocol, diverse tetra-substituted imidazoles, which are among the significant biologically active scaffolds, were synthesized in high yield within a shorter reaction time. The effect of polarity, surface acidity and extra framework Al species of the catalysts has been well demonstrated by means of pyridine FT-IR, and ²⁷Al and ¹H MAS NMR. The solvent-free synthetic protocol makes the process environmentally benign and economically viable.

S. V. National Institute of Technology, Ichchhanath, Surat

Mandvi Science College, Mandvi – 394160, Surat, India

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DISCLAIMER

“ORGANIC SPECTROSCOPY INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione—Synthesis and Crystallographic Studies

Synthesis of the (S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione (4)

(S)-piperazine-2-carboxylic acid dihydrochloride (5, 700 mg, 3.45 mmol, 1 equiv.) was dispersed in 50 mL of 1:1 water:dioxane mixture and treated with sodium hydroxide (276 mg, 6.89 mmol, 2 equiv.). After dissolution of the starting material, 4-chlorobenzoyl chloride (6, 0.49 mL, 3.79 mmol, 1.1 equiv.) was added and reaction mixture was stirred in room temperature for 18 h. The next day, the disappearance of starting material and formation of (S)-4-(4-chlorobenzoyl)piperazine-2-carboxylic acid (7) was confirmed by LRMS-ESI spectra. Then, isatoic anhydride (8, 1.69 g, 10.34 mmol, 3 equiv.) was added, followed by addition of sodium carbonate (1.10 g, 10.34 mmol, 3 equiv.); the reaction mixture was heated in 60 °C for 18 h. The following day, formation of the (S)-1-(2-aminobenzoyl)-4-(4-chlorobenzoyl)piperazine-2-carboxylic acid 9 was confirmed by LRMS-ESI spectra. The volatiles were evaporated under reduced pressure, then the residue was co-evaporated with toluene (3 × 50 mL) and dissolved in dry DMF. For cyclization of 9, HATU (3.93 g, 10.34 mmol, 3 equiv.) and DIPEA (1.80 mL, 10.34 mmol, 3 equiv.) were added, and reaction mixture was stirred in room temperature for 18 h. The day after, the volatiles were evaporated under reduced pressure and residue was dissolved in water:ethyl acetate biphasic system. The organic phase was washed with water (2 × 50 mL), 0.5 M HCl (3 × 50 mL), saturated sodium bicarbonate (1 × 50 mL), and dried over magnesium sulphate. The crude product dissolved in ethyl acetate was evaporated with silica gel (2 g) and purified by column chromatography using hexane:ethyl acetate 2:8 v/v mixture, followed by pure ethyl acetate. Yield: 711 mg (56%). 1H-NMR (500 MHz, DMSO-d6): 10.55, 10.45 (2 × s, 2 × NH); 7.80–7.70 (m, 1H, HAr); 7.70–7.40 (m, 5H, HAr); 7.30–7.20 (m, 1H, HAr); 7.20–7.00 (m, 1H, HAr); 4.45–3.30 (m, 7H, 3 × CH2, 1 × CH); 13C-NMR (125 MHz, DMSO-d6): 170.5, 169.5, 166.6, 136.6, 135.0, 134.2, 132.3, 130.9, 129.3, 129.0, 128.5, 128.3, 125.6, 124.0, 120.9, 51.7, 42.7, 42.2, 38.2; HRMS (ESI): m/z [M + H]+ calcd. for C19H17ClN3O3: 370.09530, 372.09235, found: 370.09517, 372.09206; m.p. 248–250 °C. [α]20D$$ = +290 (c 1.0, DMSO). IR (KBr): cm−1 3465, 3369, 3229, 3160, 3109, 3068, 2909, 2866, 1694, 1657, 1620, 1521, 1477, 1431, 1407, 1339, 1303, 1262, 1219, 1181, 1162, 1092, 1035, 1010.

Molbank 2017, 2017(4), M964; doi: 10.3390/M964

Communication

(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione—Synthesis and Crystallographic Studies

Adam Mieczkowski 1,*, Damian Trzybiński 2, Marcin Wilczek 3, Mateusz Psurski 4, Maciej Bagiński 1,3, Bartosz Bieszczad 1,3, Magdalena Mroczkowska 1,3 and Krzysztof Woźniak 2

1

Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland

2

Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland

3

Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland

4

Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigl, 53-114 Wroclaw, Poland

*

Correspondence: Tel.: +48-22-592-35-06; Fax: +48-22-592-21-90

Received: 12 October 2017 / Accepted: 25 October 2017 / Published: 27 October 2017

Abstract

: 

(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione was obtained in a three-step, one-pot synthesis, starting from optically pure (S)-2-piperazine carboxylic acid dihydrochloride. Selective acylation of the β-nitrogen atom followed by condensation with isatoic anhydride and cyclization with HATU/DIPEA to a seven-member benzodiazepine ring, led to the tricyclic benzodiazepine derivative. Crystallographic studies and initial biological screening were performed for the title compound.

Keywords:

 (S)-2-piperazinecarboxylic acid; tricyclic benzodiazepines; isatoic anhydride; cytotoxicity

http://www.mdpi.com/1422-8599/2017/4/M964/htm
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