Saturday 30 January 2016

Synthesis and Diels–Alder Reactivity of Substituted [4]Dendralenes





Figure
Scheme 1. Diene-Transmissive Diels–Alder Cycloaddition Sequences of [3]- and [4]Dendralene with the Prototypical Olefinic Dienophile


Abstract Image



The first synthesis of all five possible monomethylated [4]dendralenes has been achieved via two distinct synthetic strategies. The Diels–Alder chemistry of these new dendralenes (as multidienes) with an electron poor dienophile, N-methylmaleimide (NMM), has been studied. Thus, simply upon mixing the dendralene and an excess of dienophile at ambient temperature in a common solvent, sequences of cycloadditions result in the rapid generation of complex multicyclic products. Distinct product distributions are obtained with differently substituted dendralenes, demonstrating that dendralene substitution influences the pathway followed, when a matrix of mechanistic possibilities exists. Dendralene site selectivities are traced to electronic, steric and conformational effects, thereby allowing predictive tools for applications of substituted dendralenes in future synthetic endeavors.

Figure

Scheme 2. Diene-Transmissive Diels–Alder Cycloaddition Sequences of [4]Dendralene (1) with the Dienophile N-Methylmaleimide (NMM)




Figure

Scheme 3. Syntheses of the Five Mono-Methyl-Substituted-[4]Dendralenes


3 Diels-Alder reactions in 1 go

 DIELS ALDER CASCADE 01.29.2016.gif
FROM https://naturalproductman.wordpress.com/2016/01/29/11137/









Tris-adduct 36
An analytic sample of 36 was obtained by recrystallization from EtOAc/hexane to give colorless needles, mp 255–257 °C; Rf 0.20 (EtOAc, 100%);  
 
1H NMR (300 MHz, CDCl3) δ 3.22 (dd, J = 8.6, 5.9 Hz, 1H), 3.19–3.07 (m, 3H), 3.04–2.91 (m, 5H), 2.90 (s, 6H), 2.86 (s, 3H), 2.65 (ddd, J = 14.1, 13.4, 5.4 Hz, 1H), 2.35 (ddd, J = 14.3, 5.0, 2.5 Hz, 1H), 2.16–2.05 (m, 2H), 2.03–1.91 (m, 1H), 1.85–1.74 (m, 1H), 1.54 (d, J = 6.8 Hz, 3H) ppm;  
 
13C NMR (75 MHz, CDCl3) δ 179.7 (C), 178.5 (C), 178.4 (C), 178.3 (C), 177.0 (C), 176.6 (C), 130.8 (C), 130.8 (C), 44.4 (CH), 43.4 (CH), 40.8 (CH), 40.6 (CH), 40.3 (CH), 39.2 (CH), 38.8 (CH), 33.7 (CH), 29.0 (CH), 25.0 (CH3), 24.9 (CH3), 24.8 (CH3), 24.7 (CH2), 24.4 (CH2), 23.1 (CH2), 16.5 (CH3) ppm; 
 
 
IR (KBr disc) νmax = 2961, 2948, 2842, 1770, 1695, 1435, 1383, 1286 cm–1
 
 
LRMS (70 eV, EI) m/z (%) 453 ([M]+•, 100%), 438 (7), 342 (33), 256 (14), 112 (39); 
 
 
HRMS calc for C24H27N3O6 [M]+• 453.1900, found 453.1905.

Synthesis and Diels–Alder Reactivity of Substituted [4]Dendralenes

Research School of Chemistry, The Australian National University, Canberra, ACT 2601, Australia
School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
J. Org. Chem., Article ASAP
DOI: 10.1021/acs.joc.5b02583
Publication Date (Web): January 12, 2016
Copyright © 2016 American Chemical Society
ACS Editors' Choice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
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Tuesday 26 January 2016

Reductive amination of furfural to furfurylamine using aqueous ammonia solution and molecular hydrogen: an environmentally friendly approach

Green Chem., 2016, 18,487-496
DOI: 10.1039/C5GC01352F, Paper
Maya Chatterjee, Takayuki Ishizaka, Hajime Kawanami
An efficient process was developed to obtain furfurylamine with very high yield ([similar]92%) through the reductive amination of furfural under a mild reaction condition.

 http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C5GC01352F?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract




A simple and highly efficient method was developed for the transformation of furfural (a biomass derived aldehyde) to furfurylamine by reductive amination using an aqueous solution of ammonia and molecular hydrogen as an amine source and a reducing agent, respectively. By choosing a suitable catalyst, such as Rh/Al2O3, and reaction conditions, a very high selectivity of furfurylamine (∼92%) can be achieved within the reaction time of 2 h at 80 °C. A detailed analysis of the reaction system sheds some light on the reaction pathway and provides an understanding about each elementary step. The reaction was believed to proceed via an imine pathway although no such intermediate was detected because of the highly reactive nature. Optimization of different reaction parameters such as hydrogen pressure, temperature and substrate/ammonia mole ratio is shown to be critical to achieve high selectivity of furfurylamine. Time-dependent reaction profiles suggested that a Schiff base type intermediate was in the detectable range, which offers indirect evidence of the formation of imine. Competitive hydrogenation and amination of an aldehyde group were strongly dictated by the nature of the metal used. The studied protocol represents an environmentally benign process for amine synthesis, which can be effectively extended to the other aldehydes also. The studied catalyst could be recycled successfully without any significant loss of catalytic activity.


Graphical abstract: Reductive amination of furfural to furfurylamine using aqueous ammonia solution and molecular hydrogen: an environmentally friendly approach





Reductive amination of furfural to furfurylamine using aqueous ammonia solution and molecular hydrogen: an environmentally friendly approach

*
Corresponding authors
a
Microflow Chemistry Group, Research Institute for Chemical Process Technology, AIST Tohoku, 4-2-1, Nigatake, Miyagino-ku, Japan 
E-mail: c-maya@aist.go.jp, h-kawanami@aist.go.jp
Fax: +81 22 237 5388 
Tel: +81 22 237 5213
b
CREST, Japan Science and Technology (JST), 4-1-8, Honcho, Kawaguchi, Japan
Green Chem., 2016,18, 487-496

DOI: 10.1039/C5GC01352F     /////////////


Hydrogenative cyclization of levulinic acid into [gamma]-valerolactone by photocatalytic intermolecular hydrogen transfer

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Hydrogenative cyclization of levulinic acid into [gamma]-valerolactone by photocatalytic intermolecular hydrogen transfer



Green Chem., 2016, Advance Article
DOI: 10.1039/C5GC02971F, Communication
Hongxia Zhang, Min Zhao, Tianjian Zhao, Li Li, Zhenping Zhu
A hydrogenation-dehydrogenation coupling process efficiently realized an intermolecular hydrogen transfer from isopropanol to LA under photocatalytic conditions over gold-loaded TiO2 catalysts.

 click
 http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C5GC02971F?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract





 The hydrogenative cyclization of levulinic acid (LA) into γ-valerolactone (GVL) is an attractive route toward the use of renewable bio-sources but it normally suffers from the consumption of H2. In this study, we report that an intermolecular hydrogen transfer from isopropanol to LA can be realized efficiently under photocatalytic conditions over gold-loaded TiO2 catalysts. In this manner, isopropanol is dehydrogenated as acetone and pinacol with the total selectivity of >99%, whereas LA is hydrogenated and cyclized as GVL with the selectivity of up to 85%. In this reaction process, the production of GVL is mediated with hydrogenated dehydration of LA into an acetyl propionyl radical, which is further hydrogenated and cyclized as GVL. This hydrogenation–dehydrogenation coupling process provides an atom-economical green way for the conversion of LA into GVL.

Hydrogenative cyclization of levulinic acid into γ-valerolactone by photocatalytic intermolecular hydrogen transfer

Hongxia Zhang,*ab   Min Zhao,ab   Tianjian Zhao,ab   Li Lib and  Zhenping Zhu*b  
*
Corresponding authors
a
Institute of Application Chemistry, Shanxi University, Taiyuan 030006, China 
E-mail: hxzhang@sxu.edu.cn
b
State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001, China 
E-mail: zpzhu@sxicc.ac.cn
Green Chem., 2016, Advance Article

DOI: 10.1039/C5GC02971F



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Oxidative conversion of glucose to gluconic acid by iron(III) chloride in water under mild conditions

Green Chem., 2016, Advance Article
DOI: 10.1039/C5GC02614H, Communication
Hongdan Zhang, Ning Li, Xuejun Pan, Shubin Wu, Jun Xie
A simple method to oxidize glucose into gluconic acid in a concentrated FeCl3 solution under mild conditions was developed

 click

.

Oxidative conversion of glucose to gluconic acid by iron(III) chloride in water under mild conditions

 

 

A simple method was demonstrated to oxidize glucose into gluconic acid in a concentrated FeCl3 solution. 
The maximum gluconic acid yield (52.3%) was achieved in the 40% FeCl3solution at 110 °C in 4 hours. 
Formic and acetic acids were the main coproducts with an yield of 10–20%.



Oxidative conversion of glucose to gluconic acid by iron(III) chloride in water under mild conditions

Hongdan Zhang,abc   Ning Li,b   Xuejun Pan,*b   Shubin Wu*c and   Jun Xiea  
*
Corresponding authors
a
Institute of New Energy and New Material, Key Laboratory of Energy Plants Resource and Utilization, Ministry of Agriculture, Key Laboratory of Biomass Energy of Guangdong Regular Higher Education Institutions, South China Agricultural University, Guangzhou 510642, P.R. China
b
Department of Biological Systems Engineering, University of Wisconsin-Madison, 460 Henry Mall, Madison, USA
E-mail: xpan@wisc.edu
Tel: +1 (608) 262-4951
c
State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510640, P.R. China
E-mail: shubinwu@scut.edu.cn
Tel: +86 (020)22236808
Green Chem., 2016, Advance Article

DOI: 10.1039/C5GC02614H






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Monday 18 January 2016

An efficient epoxidation of terminal aliphatic alkenes over heterogeneous catalysts: when solvent matters





An efficient epoxidation of terminal aliphatic alkenes over heterogeneous catalysts: when solvent matters


Catal. Sci. Technol., 2016, Advance Article
DOI: 10.1039/C5CY01639H, Paper
C. Palumbo, C. Tiozzo, N. Ravasio, R. Psaro, F. Carniato, C. Bisio, M. Guidotti
With a peculiar combination of catalyst/oxidant/solvent, it is possible to obtain good yields and excellent selectivities in the epoxidation of 1-octene.

see..............http://pubs.rsc.org/en/Content/ArticleLanding/2016/CY/C5CY01639H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2Fcy+%28RSC+-+Catalysis+Science+%26+Technology+latest+articles%29#!divAbstract


The epoxidation of unfunctionalized terminal aliphatic alkenes over heterogeneous catalysts is still a challenging task. Due to the tuning of a peculiar catalyst/oxidant/solvent combination, it was possible to attain good alkene conversions (73%) and excellent selectivity values (>98%) in the desired terminal 1,2-epoxide. Over the titanium–silica catalyst and in the presence of tert-butylhydroperoxide, the use of α,α,α-trifluorotoluene as an uncommon non-toxic solvent was the key factor for a marked enhancement of selectivity. The titanium–silica catalyst was efficiently recycled and reused after a gentle rinsing with fresh solvent.









An efficient epoxidation of terminal aliphatic alkenes over heterogeneous catalysts: when solvent matters

C. Palumbo,a   C. Tiozzo,a   N. Ravasio,a   R. Psaro,a   F. Carniato,b  C. Bisioab and   M. Guidotti*a  

*
Corresponding authors
a
CNR-Istituto di Scienze e Tecnologie Molecolari, Via C. Golgi 19, 20133 Milano, Italy
E-mail: m.guidotti@istm.cnr.it
b
Dipartimento di Scienze e Innovazione Tecnologica and Nano-SISTEMI Interdisciplinary Centre, Università del Piemonte Orientale “A. Avogadro”, Viale Teresa Michel 11, 15121 Alessandria, Italy
Catal. Sci. Technol., 2016, Advance Article

DOI: 10.1039/C5CY01639H
























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Friday 15 January 2016

TSRI Chemists Devise Powerful New Method for Modifying Drug Molecules

http://www.scripps.edu/news/press/images/baran_phil/150111group.jpg
Chemists from The Scripps Research Institute illustrate their powerful new technique to make and modify medicines, published recently in the journal Science. Professor Phil Baran (center) holds a flask representing amines to cleave strained C–C bonds, which are depicted by a tug-of-war between co-first authors Ryan Gianatassio (left center) and Justin Lopchuk (right center) with co-authors Chung-Mao Pan (left) and Jie Wang.

 
Bicyclo[1.1.1]pentan-1-amine
177287-49-9 [RN]
22287-35-0 [RN]
Bicyclo[1.1.1]pentan-1-amine hydrochloride

 http://www.scripps.edu/news/press/2016/20160114baran.html

TSRI Chemists Devise Powerful New Method for Modifying Drug Molecules

‘Strain-release amination’ technique emerged from efforts to help Pfizer synthesize promising cancer drug candidate
LA JOLLA, CA—January 14, 2016—Chemists at The Scripps Research Institute (TSRI) have developed a versatile new technique for making modifications—especially one type of extremely difficult, but much-sought-after modification—to complex drug molecules.
The feat, reported in the January 15 issue of the journal Science, has already enabled pharma giant Pfizer to proceed with the evaluation of a promising cancer drug candidate that otherwise could not have been made in sufficient quantities.
“People from other pharma companies who have seen early drafts of this paper can’t get their hands on the supporting information fast enough,” said senior investigator Phil S. Baran, the Darlene Shiley Professor of Chemistry at TSRI. “I expect that every company in the business of making drugs will be using this chemistry soon.”
The technique, known as “strain-release amination,” also should enable the easier construction of a variety of molecules besides pharmaceuticals, including molecular probes for basic biology studies, plastics, and other materials made from organic compounds.
Pfizer’s Bottleneck
The project began with Pfizer’s request for help in synthesizing a molecule known as bicyclo[1.1.1]pentan-1-amine, which it needed to make the cancer drug candidate. The Baran laboratory frequently collaborates with Pfizer and other pharma companies to solve tough problems in medicinal and process chemistry.
Traditional methods of synthesizing bicyclo[1.1.1]pentan-1-amine left much to be desired. “Most of the previously published synthetic routes require three to five steps with toxic reagents and yield only tens of milligrams,” said Ryan Gianatassio, a PhD student at TSRI who was co-first author of the study.
Pfizer needed kilograms of bicyclo[1.1.1]pentan-1-amine for preclinical studies of its cancer drug candidate, and the company had had to shelve the drug’s development until it could make that much of it.
“We built a team of expert synthetic chemists to solve this challenging problem, including chemists from Phil Baran’s lab and Pfizer’s synthetic and process chemistry groups,” said Michael R. Collins, a senior principal scientist at the drug company’s La Jolla Laboratories.
Baran and his team, including Gianatassio and co-first author TSRI Research Associate Justin M. Lopchuk, were able to solve the supply problem for this building block, enabling a relatively quick and easy synthesis from a readily available starting compound. “Using our procedure, Pfizer easily produced over 100 grams, and they are now in a position to scale that up further and re-start that delayed drug development program,” said Gianatassio.
Adding Strained-Ring Structures
Baran realized that the new method could have much broader applications.
Bicyclo[1.1.1]pentan-1-amine is a “spring-loaded” or “strained ring” molecule, in which carbon atoms are arranged in rings at odd angles, with relatively large bond energies. Pharmaceutical chemists know that adding such a structure to a drug molecule sometimes greatly improves the drug’s properties: making it more absorbable by the gut, for example, or enabling it to resist breakdown by enzymes in the body so that it works therapeutically for longer periods.
The problem has been that, using traditional methods, the insertion of these small structures into larger drug molecules is tricky—so much so that chemists often have had to redesign the entire synthesis around the small added structure.
“The way they’ve been doing it is like decorating a Christmas tree by putting the ornaments in place first and then growing the tree around it,” said Baran. “In many cases they just won’t pursue that because of the time and labor it would take.”
Baran and his team showed that they could use their new method to directly append a strained-ring molecule favored by pharmaceutical chemists—propellane, so-called because its structure resembles a propeller—to existing larger drug molecules. “We can make that five-carbon ring structure of propellane click onto a wide range of drug molecules of a type known as secondary amines—we call that a propellerization reaction,” said Lopchuck.
“In fact, starting with a stock solution of the propellane, we can use high-throughput techniques to quickly elaborate a matrix of amine-containing compounds with the bicyclopentyl moiety, instead of painstakingly synthesizing the compounds one at a time,” Collins said.
The team went on to demonstrate similar direct modifications using two other strained-ring structures, azetidine and cyclobutane.
The TSRI researchers also found that they could use the new method to attach molecules very precisely and selectively to specific amino acids on proteins, thus in principle enabling the creation of new biologic drugs as well as new reagents that would be useful in basic biology research. “This technique opens up a world of chemistry that academic and commercial laboratories have really wanted to look into but couldn’t, due to the technical obstacles,” said Baran.
The supporting, publicly available information on strain-release amination is meant to enable chemists to start using the technique right away. A behind-the-scenes account and high-definition photos of the new reaction setup can be found on the Baran Lab Blog, Open Flask.
“This can be considered rapid bench-to-bedside chemistry because it is fundamental science that will have a positive impact on human medicine in a short period of time,” Baran said.
Other co-authors of the paper, “Strain Release Amination,” were Jie Wang, Chung-Mao Pan, Lara R. Malins and Liher Prieto of TSRI; and Thomas A. Brandt, Gary M. Gallego, Neal W. Sach, Jillian E. Spangler, Huichun Zhu and Jinjiang Zhu, of Pfizer.
The research was funded in part by Pfizer and the National Institutes of Health’s National Institute of General Medical Sciences.
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
# # #
For information:
Office of Communications
Tel: 858-784-2666
Fax: 858-784-8136
press@scripps.edu

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Org Lett. 2014 Apr 4;16(7):1884-7. doi: 10.1021/ol500635p. Epub 2014 Mar 14.

A new route to bicyclo[1.1.1]pentan-1-amine from 1-azido-3-iodobicyclo[1.1.1]pentane.

 http://pubs.acs.org/doi/abs/10.1021/ol500635p

Abstract

From a medicinal chemistry perspective, bicyclo[1.1.1]pentan-1-amine (1) has served as a unique and important moiety. Synthetically, however, this compound has received little attention, and only one scalable route to this amine has been demonstrated. Reduction of an easily available and potentially versatile intermediate, 1-azido-3-iodobicyclo[1.1.1]pentane (2), can offer both a flexible and scalable alternative to this target. Herein, we describe our scrutiny of this reportedly elusive transformation and report our ensuing success with this endeavor.







Abstract Image







Scalable Synthesis of 1-Bicyclo[1.1.1]pentylamine via a Hydrohydrazination Reaction

Pfizer Worldwide Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, California 92121, United States
Org. Lett., 2011, 13 (17), pp 4746–4748
DOI: 10.1021/ol201883z
Publication Date (Web): August 11, 2011
Copyright © 2011 American Chemical Society

 http://pubs.acs.org/doi/abs/10.1021/ol201883z

Abstract

Abstract Image
The reaction of [1.1.1]propellane with di-tert-butyl azodicarboxylate and phenylsilane in the presence of Mn(dpm)3 to give di-tert-butyl 1-(bicyclo[1.1.1]pentan-1-yl)hydrazine-1,2-dicarboxylate is described. Subsequent deprotection gives 1-bicyclo[1.1.1]pentylhydrazine followed by reduction to give 1-bicyclo[1.1.1]pentylamine. The reported route marks a significant improvement over the previous syntheses of 1-bicyclo[1.1.1]pentylamine in terms of scalability, yield, safety, and cost.










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Thursday 14 January 2016

Design, Synthesis, Antimicrobial and Anti-inflammatory Activity of N-Pyrazolyl Benzamide Derivatives

derivatives.








Synthesis of 5-amino-3-t-butyl-1-(2', 4'-dinitro)phenyl-1Hpyrazole (3)
A mixture of 4, 4-dimethyl-3-oxo-pentanenitrile (1, 34 mM), 2, 4-dinitrophenyl hydrazine hydrochloride (2, 35 mM) and 50 mL absolute ethanol along with few drops of AcOH were heated at the reflux temperature for overnight and cooled to room temperature. The mixture was evaporated under vacuum and the residue thus obtained was washed with ether, suspended in EtOAc, and treated with 1 M NaOH solution. The organic layer then separated, washed with brine, dried over anhydrous magnesium sulphate and concentrated. The solid which separated was collected, then washed with a mixture of ether and hexane to give 5-amino-3-t-butyl-1-(2', 4'-dinitro)phenyl-1H-pyrazole (3) [22].



General procedure for N-[3'-t-butyl-1'-(2", 4"-dinitro) phenylpyrazol-5'-yl] benzamide (5a-l)
To a solution of 5-amino-3-t-butyl-1-(2', 4'-dinitro)phenyl-1Hpyrazole (3, 9.3 mM) in dichloromethane (5 mL), triethyl amine (23 mM) was added drop wise. The appropriate benzoylchlorides (4a-k, 12 mM) in dichloromethane were added to the above reaction mixture drop wise and stirred for 3 hours at room temperature. The mixture was further diluted with dichloromethane and washed with water, brine followed by once again with water. Sodium sulfate was used to dry the organic layer; solvent was removed under vacuum to get the final derivatives (5a-l). All the compounds were purified over silica to get pure N-(3-tert-butyl-2, 4-dinitro-1-phenyl-1H-pyrazol-5-yl) benzamides (5a-l).




Compound characterization
N-[3'-t-butyl-1'-(2", 4"-dinitro)phenylpyrazol-5'-yl] benzamide 5a: Yield: 85%, m.p.: 190-192°C,

 IR (KBr) ν cm-1: 3362 cm-1 (NH str.), 3020 cm-1 (CH str. aromatic), 2950 cm-1 (CH str. methyl), 1643 cm-1 (NH bnd)  



1H NMR (CDCl3) δ (ppm): 1.23 (s, 9H, t-butyl), 6.18 (s, 1H, C4, pyrazole), 7.15-7.55 (m, 3H, C3', C4', C5' aromatic), 7.7-7.8 (m, 2H, C5, C6, aromatic), 7.9-8.1 (d, 2H, C2', C6', aromatic), 8.2 (s, 1H, C3, aromatic), 9.61 (bs, 1H, NH amide). 

ESI-MS (m/z): 410, 100% [M+H]+.


The intermediate compound 5-amino-3-t-butyl-1-(2', 4'-dinitro)phenyl-1H-pyrazole 3 was prepared in good yields by refluxing 4, 4-dimethyl-3-oxo-pentanenitrile 1 and 2, 4-dinitrophenyl hydrazine hydrochloride 2. The FT IR spectrum of 3 showed the presence of bands characteristic for primary amine at 3423.42 cm-1 and 3264.21 cm-1 which are attributed to the asymmetric and symmetric stretching respectively and aromatic hydrogen stretching band located at 3056.75 cm-1. The CH3 groups of t-butyl vibrations were observed at 2961.33 cm-1 and 2828.42 cm-1 and peak assigned for bending vibration of NH group was observed at 1625.94 cm-1. The1H NMR of 3 revealed a broad singlet at δ 3.77 ppm characteristic for primary amine group, multiplet at delta value of 8.05, 7.35 and 7.63 for C3, C5 and C6 aromatic protons and a pyrazolyl-C4-H as a singlet at 6.1 ppm. The nine t-butyl protons were found as singlet at δ 1.23 ppm. The EI Mass spectrum of 3 showed molecular ion peak at m/z 215.
When 5-amino-3-t-butyl-1-(2', 4'-dinitro)phenyl-1H-pyrazole 3 was stirred with substituted benzoylchlorides 4a-k in dichloromethane and triethylamine, pyrazolylbenzamides 5a-l were obtained in moderate to good yields (5j was reduced with stannous chloride to form 5l). The structures of the isolated compounds were determined by spectral methods.
The FT IR spectrum of 5a revealed characteristic NH band at 3362 cm-1, the aromatic hydrogen stretching was found at 3020 cm-1 and stretching vibrations of CH3 group of t-butyl band was noticed at 2950 cm-1. A band at 1595 cm-1 was assigned for the C=C stretching. The 1H NMR spectra displayed a broad absorption peak at δ 9.61 which was due to resonance of NH proton of amide while the pyrazol-C4-H and nine t-butyl protons appears as singlet’s at δ 6.18 and 1.23 ppm respectively. The aromatic protons appeared as doublet at δ 7.9-8.1 which indicated the resonance of C2', C6' protons. Three aromatic protons C3', C4', C5' resonated as multiplet at δ 7.15-7.55 and another multiplet at δ 7.7-7.8 integrated for two protons C5 and C6. C3 proton was observed as singlet at δ 8.2.



Design, Synthesis, Antimicrobial and Anti-inflammatory Activity of N-Pyrazolyl Benzamide Derivatives
Aneesa Fatima1*, Ravindra Kulkarni2 and Bhagavanraju Mantipragada3
1Malla Reddy College of Pharmacy, Maisammaguda, Secunderabad, Telangana, India
2SVERI College of Pharmacy, Gopalpur Ranjini Road, Gopalpur, Pandharpur, Maharashtra, India
3Sri Venkateswara College of Pharmacy, HITEC City, Madhapur, Telangana, India
Corresponding Author :Aneesa Fatima
Malla Reddy College of Pharmacy
Maisammaguda, Secunderabad
Telangana, India
Tel: +918125343156
E-mail: aneesafatima.16@gmail.com
Received: November 17, 2015; Accepted: December 07, 2015; Published: December 10, 2015
Citation: Fatima A, Kulkarni R, Mantipragada B (2015) Design, Synthesis, Antimicrobial and Anti-inflammatory Activity of N-Pyrazolyl Benzamide Derivatives. Med chem 5:521-527. doi:10.4172/2161-0444.1000311
http://www.omicsonline.org/open-access/design-synthesis-antimicrobial-and-antiinflammatory-activity-ofnpyrazolyl-benzamide-derivatives-2161-0444-1000311.php?aid=64851




Structure
Figure 1: Structure of VHw along with antibacterial activity against Bacillus subtilis (MTCC 619).
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