Cas 22996-21-0,4-METHOXY-2-NITRO-BENZALDEHYDE

-21-0Relevant articles and documents

ARYLOXYACETYLINDOLES AND ANALOGS AS ANTIBIOTIC TOLERANCE INHIBITORS

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, (/08/10)

The disclosure provides compounds and pharmaceutical compositions of aryloxyacetylindoles compounds and analogs useful for treating chronic and acute bacterial infections. Certain of the compounds are compounds of general Formula (I) (I) or a pharmaceutically acceptable salt or prodrug thereof. Certain compounds of this disclosure are MvfR inhibitors. MvfR inhibitors reduce the formation of antibiotic tolerant bacterial strains and are useful for treating Gram-negative bacterial infections and reducing the virulence of Pseudomonas aeruginosa. Methods of treating bacterial infections in a subject, including Pseudomonas aeruginosa infections, are also provided by the disclosure.

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Synthesis and Evaluation of a New Series of 8-(2-Nitroaryl)Xanthines as Adenosine Receptor Ligands

Bansal, Ranju,Kumar, Gulshan,Rohilla, Suman,Klotz, Karl-Norbert,Kachler, Sonja,Young, Louise C.,Harvey, Alan L.

, p. 241 - 250 (/08/28)

(Table presented.). A new series of 1,3-dimethylxanthine derivatives bearing 8-(2-nitroaryl) residue was synthesized and evaluated for affinity for recombinant human adenosine receptors subtypes. Nitrate esters of 7-substituted-1,3-dimethyl-8-phenylxanthines were also synthesized and tested. Introducing a nitro substituent at the 2-position of the 8-substituted phenyl ring resulted in generally low affinity for adenosine receptors (ARs), selectivity toward the A2A subtype was enhanced in some of the compounds. 8-(4-Cyclopentyloxy-5-methoxy-2-nitrophenyl)-1,3-dimethylxanthine (9e) proved to be a potent compound among the 2-nitrophenyl substituted xanthines exhibiting a Ki = 1 μM at human A2A ARs with at least 30 fold selectivity versus human A1 and A2B ARs. Replacement of 8-chloropropoxy phenyl with 8-nitrooxypropoxy phenyl resulted in a negligible change in binding affinity of the 8-substituted xanthines for various AR subtypes. Drug Dev Res 77 : 241&#;250, .

Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors

Takrouri, Khuloud,Chen, Ting,Papadopoulos, Evangelos,Sahoo, Rupam,Kabha, Eihab,Chen, Han,Cantel, Sonia,Wagner, Gerhard,Halperin, Jose A.,Aktas, Bertal H.,Chorev, Michael

, p. 361 - 377 (/04/17)

Abstract Protein-protein interactions are critical for regulating the activity of translation initiation factors and multitude of other cellular process, and form the largest block of untapped albeit most challenging targets for drug development. 4EGI-1, (E/Z)-2-(2-(4-(3,4-dichlorophenyl)thiazol-2-yl) hydrazono)-3-(2-nitrophenyl)propanoic acid, is a hit compound discovered in a screening campaign of small molecule libraries as an inhibitor of translation initiation factors eIF4E and eIF4G protein-protein interaction; it inhibits translation initiation in vitro and in vivo. A series of 4EGI-1-derived thiazol-2-yl hydrazones have been designed and synthesized in order to delineate the structural latitude and improve its binding affinity to eIF4E, and increase its potency in inhibiting the eIF4E/eIF4G interaction. Probing a wide range of substituents on both phenyl rings comprising the 3-phenylpropionic acid and 4-phenylthiazolidine moieties in the context of both E- and Z-isomers of 4EGI-1 led to analogs with enhanced binding affinity and translation initiation inhibitory activities.

Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II: Broad-spectrum antibacterial agents with reduced hERG activity

Reck, Folkert,Alm, Richard,Brassil, Patrick,Newman, Joseph,Dejonge, Boudewijn,Eyermann, Charles J.,Breault, Gloria,Breen, John,Comita-Prevoir, Janelle,Cronin, Mark,Davis, Hajnalka,Ehmann, David,Galullo, Vincent,Geng, Bolin,Grebe, Tyler,Morningstar, Marshall,Walker, Phil,Hayter, Barry,Fisher, Stewart

experimental part, p. - (/01/06)

Novel non-fluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. Aminopiperidines that have a bicyclic aromatic moiety linked through a carbon to an ethyl bridge, such as 1, generally show potent broad-spectrum antibacterial activity, including quinolone-resistant isolates, but suffer from potent hERG inhibition (IC50= 3 M for 1). We now disclose the finding that new analogues of 1 with an N-linked cyclic amide moiety attached to the ethyl bridge, such as 24m, retain the broad-spectrum antibacterial activity of 1 but show significantly less hERG inhibition (IC 50= 31 M for 24m) and higher free fraction than 1. One optimized analogue, compound 24l, showed moderate clearance in the dog and promising efficacy against Staphylococcus aureus in a mouse thigh infection model.

Ethylammonium nitrate (EAN)/Tf2O and EAN/TFAA: Ionic liquid based systems for aromatic nitration

Aridoss, Gopalakrishnan,Laali, Kenneth K.

experimental part, p. - (/11/13)

Acting as in situ sources of triflyl nitrate (TfONO2) and trifluoroacetyl nitrate (CF3COONO2), the EAN/Tf 2O and EAN/TFAA systems, generated via metathesis in the readily available ethylammonium nitrate (EAN) ionic liquid as solvent, are powerful electrophilic nitrating reagents for a wide variety of aromatic and heteroaromatic compounds. Comparative nitration experiments indicate that EAN/Tf2O is superior to EAN/TFAA for nitration of strongly deactivated systems. Both systems exhibit low substrate selectivity (K T/KB = 5-10) in (Figure presented) between values reported for covalent nitrates and preformed nitronium salts.

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QUINOXALINE COMPOUNDS AND USE THEREOF

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, (/12/08)

The present invention is related to quinoxaline compounds of Formula (I) in particular for the treatment of autoimmune disorders and/or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplantation, graft rejection or lung injuries.

Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents

Siles, Rogelio,Ackley, J. Freeland,Hadimani, Mallinath B.,Hall, John J.,Mugabe, Benon E.,Guddneppanavar, Rajsekhar,Monk, Keith A.,Chapuis, Jean-Charles,Pettit, George R.,Chaplin, David J.,Edvardsen, Klaus,Trawick, Mary Lynn,Garner, Charles M.,Pinney, Kevin G.

experimental part, p. 313 - 320 (/04/11)

Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluat

Substituted 2-nitrobenzyltrichloroacetate esters for photodirected oligonucleotide detritylation in solid films

Serafinowski, Pawel J.,Garland, Peter B.

supporting information; experimental part, p. - (/02/05)

Oligonucleotide microarray fabrication by chemical synthesis using photoacid generators in solid films could have advantages over existing methods, but has not matched the accuracy of conventional synthesis where detritylation is performed with acid solut

QUINAZOLINES FOR PDK1 INHIBITION

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Page/Page column 309-310, (/06/13)

The invention provides novel quinazoline compounds that are inhibitors of PDK1. Also provided are pharmaceutical compositions including the compounds, and methods of treating proliferative diseases, such as cancers, with the compounds or compositions.

Effect of aldehyde and methoxy substituents on nucleophilic aromatic substitution by [18F]fluoride

Shen, Bin,L?ffler, Dirk,Zeller, Klaus-Peter,übele, Michael,Reischl, Gerald,Machulla, Hans-Jürgen

, p. - (/09/18)

For a series of benzaldehydes only with a leaving group or with both a leaving group and a single methoxy substituent 18F-fluorination via nucleophilic aromatic substitution (SNAr) was studied in DMF and Me2SO. In general, the radiochemical yields were clearly higher in DMF than in Me2SO. In the fluorodehalogenation reaction (leaving group: halogen = Br, Cl), extremely low radiochemical yields were observed in Me2SO (2SO (within 3 min reaction time, 90% of the precursor was consumed; radiochemical yield = 1.0 ± 0.5%); however, in DMF oxidation was always kept at a low level during the entire reaction (13C-NMR ppm values of the aromatic carbon atom bearing the leaving group.

If you want to learn more, please visit our website 4 methoxy 2 nitrobenzaldehyde.

I am a high school student who is interested in organic chemistry.
I was searching for syntheses of indigo when I came across two interesting papers on ortho-nitration of benzaldehyde.

This is the first one:
Synthesis of 2-nitrobenzaldehyde
Concentrated HNO3 (5 mL) was cautiously added to the benzaldehyde at 0 degrees Celsius. Then the mixture was stirred for 40 min at 15 degrees Celsius. On pouring the reaction mixture into ice water, insoluble material precipitated. The precipitate was filtered out to afford the crude product.
Yield: 90%; yellow colour compound; mp: 42 degrees Ceisius; IR (KBr, cm1): CHO (), C&#;N (), C&#;H aromatic (), C=C aromatic (), NO2 ( symmetric), NO2 ( asymmetric).

Now when I saw this for the first time, I was rather skeptical because they did not provide the amount of benzaldehyde or the NMR spectra values. Also, the reaction looked unlikely since sulfuric acid was not added.

That was until I managed to search up another paper they mentioned in the references section:

5-(Benzyloxy)-4-methoxy-2-nitrobenzaldehyde (3a)
3-(Benzyloxy)-4-methoxybenzaldehyde (10 g, 41 mmol) was added cautiously to 40 mL of concentrated nitric acid at 0 ºC. The mixture was then stirred at 15 °C for 40 min. On pouring the reaction mixture into ice water, the precipitate was filtrated to afford 5-(benzyloxy)-4-methoxy-2-nitrobenzaldehyde (10.4 g, 93%) as a yellow solid. Mp 131 ºC (lit[28], mp 133 ºC). 1H NMR (CDCl3): δ 10.4 (s, 1H, CHO), 7.6 (s, 1H, Ph-H), 7.3&#;7.5 (m, 5H, Ph-H),
7.20 (s, 1H, Ph-H), 5.25 (s, 2H, PhCH2O), 4.0 (s, 3H, CH3O).

4-(Benzyloxy)-5-methoxy-2-nitrobenzaldehyde (3b) The compound was prepared in 91% yield according to the procedure for 3a using 4-(benzyloxy)-3-methoxybenzaldehyde. Mp 131 ºC (lit[28], mp 133 ºC). 1H NMR (CDCl3): δ 10.4 (s, 1H, CHO), 7.60 (s, 1H, Ph-H), 7.3&#;7.5 (m, 5H, Ph-H), 7.2 (s, 1H, Ph-H), 5.25 (s, 2H, PhCH2O), 4.0 (s, 3H, CH3O).

Now when I saw this paper I was like "what..?"
I knew that benzaldehyde is a meta-directing deactivator, so I was quite surprised that the ortho-nitration was possible in such high yields. (I don't think the the benzyloxy or methoxy groups gave much effect in regio-determination since the 3a and 3b compounds both reacted well, at least seemingly.) I looked it up on the Internet and found a few more papers on this phenomenon. It was interesting enough that I decided to try out the reaction in the school lab.

I did a dropwise addition of 7.5mL of 60% nitric acid to 2mL of benzaldehyde while stirring vigorously. The whole addition step took about 30~40 minutes, and I then left it stir for 40 minutes, making sure that the temperature stayed around 14~16 degrees Celsius. The reaction mixture when I stopped stirring it had two layers: the top one was yellow and relatively clear, but the bottom one was whitish and opaque. Then I poured the reaction mixture into ice water as they said, only to find out that there were only a few pink oily drops resting at the bottom and a big drop of transparent oil floating on the top. No precipitate resulted.

I think the transparent oil floating on the top was the benzaldehyde that did not react for some reason, but I can't seem to get a clue of what the others are and why the reaction did not take place. 
At first I thought the product did not separate because it somehow was produced in an oily state. However, coming across another paper which reacted conc. nitric acid and benzaldehyde in dichloromethane, I tried that method too only to fail again. (It said the benzaldehyde and only the HNO3 molecules react in the dichloromethane layer, so this brings an increase in the nitric acid concentration in the dichloromethane layer...)

My school isn't really into chemistry, so there are no IR or NMR equipment. We ran out of TLC plates recently, and it will take a while for them to arrive. So I'm just left with my head to assume what might have happened....

Can anybody guess or explain or at least hint about what might have happened during the experiment? I believe that my starting materials are in a fairly pure state because I just opened the benzaldehyde container lid yesterday (though it probably sat around for two years or more, of course in a dark room) and the nitric acid container lid was very tightly shut.
I didn't think that it would be such a fail since those papers "had been published," but....

P.S. It would be great if we had 2-nitrobenzaldehyde in the first place, but we don't, and the purchase would take at least a few weeks...

Thanks in advance!