3342-77-6Relevant academic research and scientific papers
Reaction of benzoyleneurea and isatoic anhydride with the Vilsmeier reagent
Prashad, Mahavir,Har, Denis,Repic, Oljan,Blacklock, Thomas J.,Chin, Jefferson A.,Shapiro, Michael J.
, p. 1313 - 1316 (1997)
A ring opening and dimerization reaction of benzoyleneurea (1) or isatoic anhydride (2) with thionyl chloride in DMF (Vilsmeier reagent), to yield N,N-dimethyl-2-(4-oxo-3(4H)-quinazolinyl)benzamide (4), is described.
Solvent- and catalyst-free N-formylations of amines at ambient condition: Exploring the usability of aromatic formates as N-formylating agents
Batuta, Shaikh,Begum, Naznin Ara
supporting information, p. 137 - 147 (2017/01/11)
A solvent- and catalyst-free N-formylation protocol has been developed for amines (1s–21s) where aromatic formates (1r–6r) were used as the N-formylating agents. The amine substrates include both primary and secondary aromatic amines (1s–19s) as well as aliphatic amine (20s) and a primary amide (21s). Structures of both the aromatic formate and amine components strongly influenced the rate of the reaction and yield of the N-formamide products. The reaction condition is mild and easy to operate. This protocol can be done smoothly under ambient conditions and gives high yield of formamide products. Furthermore, the present method cannot be applied for the formylation of thiol group (22s). This signifies its possible use for the chemoselective N-formylation of amine in the presence of thiol functionality.
A photoactive bimetallic framework for direct aminoformylation of nitroarenes
Nasir Baig,Verma, Sanny,Nadagouda, Mallikarjuna N.,Varma, Rajender S.
, p. 1019 - 1022 (2016/02/27)
A bimetallic catalyst, AgPd@g-C3N4, synthesized by reducing silver and palladium salts over graphitic carbon nitride (g-C3N4), enables the concerted reductive formylation of aromatic nitro compounds under photo-chemical conditions using formic acid, which serves the dual role of a hydrogen source and a formylating agent.
The ortho effect on the acidic and alkaline hydrolysis of substituted formanilides
Desai, Salil Dileep,Kirsch, Lee E.
, p. 471 - 488 (2015/06/30)
The kinetics of formanilides hydrolysis were determined under first-order conditions in hydrochloric acid (0.01-8 M, 20-60°C) and in hydroxide solutions (0.01-3 M, 25 and 40°C). Under acidic conditions, second-order specific acid catalytic constants were used to construct Hammett plots. The ortho effect was analyzed using the Fujita-Nishioka method. In alkaline solutions, hydrolysis displayed both first- and second-order dependence in the hydroxide concentration. The specific base catalytic constants were used to construct Hammett plots. Ortho effects were evaluated for the first-order dependence on the hydroxide concentration. Formanilide hydrolyzes in acidic solutions by specific acid catalysis, and the kinetic study results were consistent with the AAC2 mechanism. Ortho substitution led to a decrease in the rates of reaction due to steric inhibition of resonance, retardation due to steric bulk, and through space interactions. The primary hydrolytic pathway in alkaline solutions was consistent with a modified BAC2 mechanism. The Hammett plots for hydrolysis of meta- and para-substituted formanilides in 0.10 M sodium hydroxide solutions did not show substituent effects; however, ortho substitution led to a decrease in rate constants proportional to the steric bulk of the substituent.
Catalytic Mechanism of Cofactor-Free Dioxygenases and How They Circumvent Spin-Forbidden Oxygenation of Their Substrates
Hernández-Ortega, Aitor,Quesne, Matthew G.,Bui, Soi,Heyes, Derren J.,Steiner, Roberto A.,Scrutton, Nigel S.,De Visser, Sam P.
supporting information, p. 7474 - 7487 (2015/06/30)
Dioxygenases catalyze a diverse range of biological reactions by incorporating molecular oxygen into organic substrates. Typically, they use transition metals or organic cofactors for catalysis. Bacterial 1-H-3-hydroxy-4-oxoquinaldine-2,4-dioxygenase (HOD) catalyzes the spin-forbidden transfer of dioxygen to its N-heteroaromatic substrate in the absence of any cofactor. We combined kinetics, spectroscopic and computational approaches to establish a novel reaction mechanism. The present work gives insight into the rate limiting steps in the reaction mechanism, the effect of first-coordination sphere amino acids as well as electron-donating/electron-withdrawing substituents on the substrate. We highlight the role of active site residues Ser101/Trp160/His251 and their involvement in the reaction mechanism. The work shows, for the first time, that the reaction is initiated by triplet dioxygen and its binding to deprotonated substrate and only thereafter a spin state crossing to the singlet spin state occurs. As revealed by steady- and transient-state kinetics the oxygen-dependent steps are rate-limiting, whereas Trp160 and His251 are essential residues for catalysis and contribute to substrate positioning and activation, respectively. Computational modeling further confirms the experimental observations and rationalizes the electron transfer pathways, and the effect of substrate and substrate binding pocket residues. Finally, we make a direct comparison with iron-based dioxygenases and explain the mechanistic and electronic differences with cofactor-free dioxygenases. Our multidisciplinary study confirms that the oxygenation reaction can take place in absence of any cofactor by a unique mechanism in which the specially designed fit-for-purpose active-site architecture modulates substrate reactivity toward oxygen.
Carbon nanotube-gold nanohybrid catalyzed N-formylation of amines by using aqueous formaldehyde
Shah, Nimesh,Gravel, Edmond,Jawale, Dhanaji V.,Doris, Eric,Namboothiri, Irishi N.N.
, p. 2201 - 2205 (2014/08/18)
The N-formylation of a variety of primary and secondary amines by using aqueous formaldehyde at room temperature in open air affords the corresponding formamides in excellent yield under the catalytic influence of a gold-carbon nanotube nanohybrid. The reaction is also marked by excellent chemoselectivity, low catalyst loading, and recyclability of the catalyst.
Highly efficient N-formylation of amines with ammonium formate catalyzed by nano-Fe3O4 in PEG-400
Wang, Zhao-Gang,Lu, Ming
, p. 1234 - 1240 (2014/01/06)
A simple and efficient protocol for the formylation of amines with ammonium formate with excellent yields catalyzed by Fe3O4 nanoparticles in PEG-400 is described. Notably, this method shows excellent activity and chemoselectivity for the formylation of primary and secondary arylamines. Moreover, the nano-Fe3O4 catalyst and PEG-400 could be easily recovered and reused.
Ketoprofen-induced formation of amino acid photoadducts: Possible explanation for photocontact allergy to ketoprofen
Karlsson, Isabella,Persson, Elin,Ekebergh, Andreas,M?rtensson, Jerker,B?rje, Anna
, p. 1294 - 1303 (2014/08/05)
Photocontact allergy is a well-known side effect of topical preparations of the nonsteroidal anti-inflammatory drug ketoprofen. Photocontact allergy to ketoprofen appears to induce a large number of photocross allergies to both structurally similar and structurally unrelated compounds. Contact and photocontact allergies are explained by structural modification of skin proteins by the allergen. This complex is recognized by the immune system, which initiates an immune response. We have studied ketoprofen's interaction with amino acids to better understand ketoprofen's photoallergenic ability. Irradiation of ketoprofen and amino acid analogues resulted in four different ketoprofen photodecarboxylation products (6-9) together with a fifth photoproduct (5). Dihydroquinazoline 5 was shown to be a reaction product between the indole moiety of 3-methylindole (Trp analogue) and the primary amine benzylamine (Lys analogue). In presence of air, dihydroquinazoline 5 quickly degrades into stable quinazolinone 12. The corresponding quinazolinone (17) was formed upon irradiation of ketoprofen and the amino acids N-acetyl-l-Trp ethyl ester and l-Lys ethyl ester. The formation of these models of an immunogenic complex starts with the ketoprofen-sensitized formation of singlet oxygen, which reacts with the indole moiety of Trp. The formed intermediate subsequently reacts with the primary amino functionality of Lys, or its analogue, to form a Trp-Lys adduct or a mimic thereof. The formation of a specific immunogenic complex that does not contain the allergen but that can still induce photocontact allergy would explain the large number of photocross allergies with ketoprofen. These allergens do not have to be structurally similar as long as they can generate singlet oxygen. To the best of our knowledge, there is no other suggested explanation for ketoprofen's photoallergenic properties that can account for the observed photocross allergies. The formation of a specific immunogenic complex that does not contain the allergen is a novel hypothesis in the field of contact and photocontact allergy.
Aniline mediated oxidative C-C bond cleavage of α-alkoxy aldehydes in air and a model reaction for the synthesis of α-(d)-amino acid derivatives
Hu, Bin,Li, Yunfeng,Li, Zhongjun,Meng, Xiangbao
supporting information, p. 4138 - 4141 (2013/07/05)
A metal-free and 4-methyl aniline mediated method for the oxidative C-C bond cleavage has been developed. The reaction proceeds in air using molecular oxygen as the oxidant, affording one-carbon shortened esters in moderate to good yields within a short time. Moreover, it provides a model reaction for the highly enantioselective synthesis of (d)-serine esters by combining with a l-proline catalyzed Mannich reaction.
Mild and convenient N-formylation protocol in water-containing solvents
Aleiwi, Bilal A.,Mitachi, Katsuhiko,Kurosu, Michio
, p. 2077 - 2081 (2013/05/08)
We have realized that N-formylations of free amines of some drug leads can improve PK/PD property of parent molecules without decreasing their biological activities. In order to selectively formylate primary amines of polyfunctional molecules, we have sought a mild and convenient formylation reaction. In our screening of N-formylation of an α-amino acid, l-phenylalanine, none of formylation conditions reported to date yielded the desired HCO-l-Phe-OH with satisfactory yield. N-formylations of amino acids with HCO2H require a water-containing media and suppress polymerization reactions due to the competitive reactions among carboxylic acids. We found that N-formylations of α-amino acids could be achieved with a water-soluble peptide coupling additive, an Oxyma derivative, (2,2-dimethyl-1,3-dioxolan-4-yl)methyl-2-cyano-2- (hydroxyimino)acetate (2), EDCI, and NaHCO3 in water or a mixture of water and DMF system, yielding N-formylated α-amino acids with excellent yields. Moreover, these conditions could selectively formylate primary amines over secondary amines at a controlled temperature. A usefulness of these conditions was demonstrated by selective formylation of daptomycin antibiotic which contains three different amino groups.
