41564-63-0Relevant academic research and scientific papers
Practical Chemoselective Acylation: Organocatalytic Chemodivergent Esterification and Amidation of Amino Alcohols with N-Carbonylimidazoles
Brown, Hailee,Heller, Stephen T.,Light, Christina,Medlin, Abigail,Nelson, Hope,Richard, William
supporting information, p. 22818 - 22825 (2021/09/13)
Chemoselective transformations are a cornerstone of efficient organic synthesis; however, achieving this goal for even simple transformations, such as acylation reactions, is often a challenge. We report that N-carbonylimidazoles enable catalytic chemodivergent aniline or alcohol acylation in the presence of pyridinium ions or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), respectively. Both acylation reactions display high and broad chemoselectivity for the target group. Unprecedented levels of chemoselectivity were observed in the DBU-catalyzed esterification: A single esterification product was obtained from a molecule containing primary aniline, alcohol, phenol, secondary amide, and N?H indole groups. These acylation reactions are highly practical as they involve only readily available, inexpensive, and relatively safe reagents; can be performed on a multigram scale; and can be used on carboxylic acids directly by in situ formation of the acylimidazole electrophile.
Discovery of trisubstituted pyrazolines as a novel scaffold for the development of selective phosphodiesterase 5 inhibitors
Abdel-Halim, Mohammad,Tinsley, Heather,Keeton, Adam B.,Weam, Mohammed,Atta, Noha H.,Hammam, Mennatallah A.,Hefnawy, Amr,Hartmann, Rolf W.,Engel, Matthias,Piazza, Gary A.,Abadi, Ashraf H.
, (2020/10/12)
Celecoxib, is a selective cyclooxygenase-2 (COX2) inhibitor with a 1,5-diaryl pyrazole scaffold. Celecoxib has a better safety profile compared to other COX2 inhibitors having side effects of systemic hypertension and thromboembolic complications. This may be partly attributed to an off-target activity involving phosphodiesterase 5 (PDE5) inhibition and the potentiation of NO/cGMP signalling allowing coronary vasodilation and aortic relaxation. Inspired by the structure of celecoxib, we synthesized a chemically diverse series of compounds containing a 1,3,5-trisubstituted pyrazoline scaffold to improve PDE5 inhibitory potency, while eliminating COX2 inhibitory activity. SAR studies for PDE5 inhibition revealed an essential role for a carboxylic acid functionality at the 1-phenyl and the importance of the non-planar pyrazoline core over the planar pyrazole with the 5-phenyl moiety tolerating a range of substituents. These modifications led to new PDE5 inhibitors with approximately 20-fold improved potency to inhibit PDE5 and no COX-2 inhibitory activity compared with celecoxib. PDE isozyme profiling of compound 11 revealed a favorable selectivity profile. These results suggest that trisubstituted pyrazolines provide a promising scaffold for further chemical optimization to identify novel PDE5 inhibitors with potential for less side effects compared with available PDE5 inhibitors used for the treatment of penile erectile dysfunction and pulmonary hypertension.
Solid state aldol reactions of solvated and unsolvated lithium pinacolone enolate aggregates
Pang, Huan,Williard, Paul G.
, (2020/01/13)
We reported the first systematic study of the solid-state aldol reactions of solvated and unsolvated lithium pinacolone enolate with a variety of solid aromatic aldehydes utilizing a mortar and pestle condition in comparison with the simple ball milling condition or tetrahydrofuran (THF) solution condition. In solution, the reactions are highly-selective with the aldol condensation product at room temperature. Under the condition of mortar and pestle, the reactions with unsolvated lithium pinacolone enolate showed the mixture of aldol condensation product and aldol addition product at room temperature. With the usage of solvated lithium pinacolone enolate, higher yields for most substrates were obtained. Furthermore, repeating the reactions under a simple ball billing condition with no other precautions at room temperature, we achieved high selectivity and yield of products for all substrates, indicating the powerful ability and the utility of solid-state, mechanochemical aldol reaction conditions.
A new method of formation of tributyl-β-keto-and tributyl-β-alkoxycarbonylalkylidenephosphorane from tributyl[(trimethylsilyl) methylene]phosphorane and their application in the wittig reaction
Lukaszewicz, Ewa,Skrzyska, Anna,Majewski, Piotr
, p. 194 - 198 (2015/05/19)
A new and efficient method of the synthesis of tributyl-β-keto- and tributyl-β-alkoxycarbonylalkylidenephosphorane via treatment of tributyl[(trimethylsilyl)- methylene]phosphorane with acid chlorides or chloroformate is described. These compounds have been studied less often than their triphenyl analogues (Maryanoff and Reitz, Chem Rev 1989, 89, 870; Taillefer and Cristau, Top Curr Chem, 2003, 229, 41; Appel, Loos, and Mayr, J Am Chem Soc 2009, 131, 704) because trialkyl-stabilized ylides are very reactive, highly perishable, and more difficult to synthesize. This paper also presents the reaction of in situ generated tributyl-β-keto- and tributyl-β-alkoxycarbonylalkylidenephosphoranes with p-nitrobenzaldehyde as a model aldehyde to obtain α,β-unsaturated ketones and esters. All reactions result in Wittig products in a completely E-stereoselective manner.
A NOVEL NUCLEOPHILIC SUBSTITUTION OF THE FORMYL GROUP IN p-NITROBENZALDEHYDE WITH SOME CARBANIONS
Iwasaki, Genji,Saeki, Seitaro,Hamana, Masatomo
, p. 173 - 176 (2007/10/02)
p-Nitrobenzaldehyde reacts with some active methylene compounds in the presence of a strong base at low temperatures to give p-substituted nitrobenzenes by the two-step course involving the initial formation of the aldol adducts and the subsequent displacement of the carbinol moieties with excess carbanions.
Radical and Ionic Nucleophilic Substitution Reactions on α-Alkyl-γ-(p-nitrophenyl)allyl Derivatives
Barker, Steven D.,Norris, Robert K.
, p. 527 - 544 (2007/10/02)
The nature of the reaction between α-alkyl-γ-(p-nitrophenyl)allyl chlorides (1)-(3), which have the general form p-O2NC6H4CH=CHCH(Cl)R, and a variety of nucleophiles depends on the alkyl group R and the nucleophile.The chloride (1) (R = Me) undergoes ionic (SN2 and subsequent Michael addition) processes with the salt (7) of 2-nitropropane to give products (15) and (16) whereas the chloride (2) (R = Pri) gives a mixture of products (17) and (18) which are shown to arise by a radical-chain nucleophilic substitution process, with allylic rearrangement-an SRN1' reaction- and ionic processes respectively.The chloride (3) (R = But) gives the SRN1' product (25) with the salt (7).Other nucleophiles with (2) and (3) appear to react by ionic (SN2 and SN2') and/or SRN1' processes; e.g. (3) gives an excellent yield of the malononitrile (32) by an SN2' process when treated with the sodium salt (9).
