- Synthesis, Reactivity and Electronic Properties of Quinazolin-2-one-Based N-Heterocyclic Carbenes
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The electronic properties of a new member F of the family of cyclic (aryl)(amido)carbenes (CArAmC) have been determined. Suitable precursors can easily be obtained by a straightforward synthesis starting from 2-nitrobenzaldehyde (5). Metal complexes (14, 15) and chalcogen adducts (12, 13) were prepared and their spectroscopic data were evaluated and compared with those reported for CArAmCs (C, D) and the mixed (amino)(amido)carbene E which is a constitutional isomer of the newly reported carbene F. The IR spectroscopic determination indicates an unexceptional TEP value of 2055 cm?1, whereas the strong π-accepting character is reflected by a chemical shift of δ(77Se) 936 ppm for the Se-adduct 12 a. However, a significant degree of electrophilic reactivity of the in situ-generated carbene F was not observed, as, for example, no cyclopropanation reactions with olefins could be detected. DFT calculations provide a rationale for these experimental observations.
- Brüggemann, Peter,Mzyk, Karol,Molter, Marius,Nellesen, Joscha,Schaper, Klaus,Ganter, Christian
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supporting information
(2021/11/30)
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- Synthesis of substituted 3,4-dihydroquinazolinonesviaa metal free Leuckart-Wallach type reaction
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The 3,4-dihydroquinazolinone (DHQ) moiety is a highly valued scaffold in medicinal chemistry due to the vast number of biologically-active compounds based on this core structure. Current synthetic methods to access these compounds are limited in terms of diversity and flexibility and often require the use of toxic reagents or expensive transition-metal catalysts. Herein, we describe the discovery and development of a novel cascade cyclization/Leuckart-Wallach type strategy to prepare substituted DHQs in a modular and efficient process using readily-available starting materials. Notably, the reaction requires only the addition of formic acid or acetic acid/formic acid and produces H2O, CO2and methanol as the sole reaction byproducts. Overall, the reaction provides an attractive entry point into this important class of compounds and could even be extended to isotopic labellingviathe site-selective incorporation of a deuterium atom.
- Bokale-Shivale, Suvarna,Amin, Mohammad A.,Sawant, Rajiv T.,Stevens, Marc Y.,Turanli, Lewend,Hallberg, Adam,Waghmode, Suresh B.,Odell, Luke R.
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p. 349 - 353
(2021/02/09)
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- Synthesis of Urea Derivatives from CO2 and Silylamines
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A series of thirty-three N,N′-diaryl, dialkyl, and alkyl-aryl ureas have been prepared in pyridine or toluene by reaction of silylamines with CO2. This protocol is shown to provide facile access to 13C-labeled ureas, as well as chiral and macrocyclic ureas. These reactions proceed through initial generation of the corresponding silylcarbamates, which subsequently react with silylamine under thermal conditions to afford the thermodynamically favored urea and disilyl ether.
- Xu, Maotong,Jupp, Andrew R.,Ong, Maegan S. E.,Burton, Katherine I.,Chitnis, Saurabh S.,Stephan, Douglas W.
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supporting information
p. 5707 - 5711
(2019/04/16)
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- Effective approach to ureas through organocatalyzed one-pot process
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An efficient approach to N, N′-unsymmetrically substituted ureas 9 has been developed through the ammonolysis process of N-Boc protected anilines 7 with amines prompted by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). Moreover, a convenient protocol for the
- Wang, Mingliang,Han, Jilai,Si, Xiaojia,Hu, Yimin,Zhu, Jidong,Sun, Xun
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supporting information
p. 1614 - 1618
(2018/03/28)
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- Synthesis of 11C-labelled ureas by palladium(II)-mediated oxidative carbonylation
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Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [11C]carbon monoxide. Starting with amines and [11C]carbon monoxide, both symmetrical and unsymmetrical 11C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [11C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/μmol-319 GBq/μ mol). DFT calculations were found to support a reaction mechanism proceeding through an 11C-labelled isocyanate intermediate.
- Roslin, Sara,Brandt, Peter,Nordeman, Patrik,Larhed, Mats,Odell, Luke R.,Erikssoni, Jonas
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- Heteroatom insertion into 3,4-dihydro-1 H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase
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Aldosterone synthase (CYP11B2) catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone. CYP11B2 is regarded as a new target for several cardiovascular diseases which are associated with chronically elevated aldosterone levels such as hypertension, congestive heart failure and myocardial fibrosis. In this paper, we optimized heterocycle substituted 3,4-dihydropyridin-2(1H)-ones as CYP11B inhibitors by systematic introduction of heteroatoms and by bioisosteric exchange of the lactame moiety by a sultame moiety. The most promising compounds regarding inhibition of human CYP11B2 and selectivity versus human enzymes CYP11B1, CYP17, and CYP19 were tested for inhibition of rat CYP11B2. Thus, we discovered compounds 4 and 9 which show potent inhibition of hCYP11B2 (IC50 1 nM) and the corresponding rat enzyme (4: 64%, 9: 51% inhibition, at 2. 2 μM).
- Grombein, Cornelia M.,Hu, Qingzhong,Rau, Sabrina,Zimmer, Christina,Hartmann, Rolf W.
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supporting information
p. 788 - 796
(2015/02/19)
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- Lanthanide-catalyzed cyclocarbonylation and cyclothiocarbonylation: A facile synthesis of benzannulated 1,3-diheteroatom five- and six-membered heterocycles
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La[N(SiMe3)2]3 proves to be an efficient catalyst system for the cyclocarbonylation of 1,2-disubstituted benzenes with isocyanates. In this approach, aryl/alkyl isocyanates react with o-phenylenediamine, o-aminophenol, o-aminothiophenol, catechols and anilines ortho-substituted by CH2NH2 and CONH2 to form, respectively, the corresponding benzimidazolones, benzoxazolones, benzothiazolones, benzodioxolones, 3,4-dihydroquinazolin-2(1H)-one, and quinazolinediones. These results represent the first example of lanthanide-catalyzed carbonylation. This methodology is also applicable for the preparation of various benzannulated 1,3-diheteroatom cyclic thioketones starting from aryl/alkyl isothiocyanates or CS2 in good to excellent yields. Based on the results of experiments performed using an o-aminobenzamido dianion lanthanide complex, a general mechanism, involving the tandem reaction of two lanthanide-ligand bonds with one heterocumulene molecule, is proposed as well.
- Jing, Yufeng,Liu, Ruiting,Lin, Yanghui,Zhou, Xigeng
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p. 1117 - 1125
(2014/08/18)
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- Benzoylureas as removable cis amide inducers: Synthesis of cyclic amides via ring closing metathesis (RCM)
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Rapid and high yielding synthesis of medium ring lactams was made possible through the use of a benzoylurea auxiliary that serves to stabilize a cisoid amide conformation, facilitating cyclization. The auxiliary is released after activation under the mild conditions required to deprotect a primary amine, such as acidolysis of a Boc group in the examples given here. This methodology is a promising tool for the synthesis of medium ring lactams, macrocyclic natural products and peptides.
- Brady, Ryan M.,Khakham, Yelena,Lessene, Guillaume,Baell, Jonathan B.
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p. 656 - 658
(2011/03/22)
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- Catalytic oxidative carbonylation of arylamines to ureas with W(CO) 6/I2 as catalyst
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The oxidative carbonylation of aniline to N,N'-diphenylurea was carried out by using W(CO)6 as the catalyst, I2 as the oxidant, CO as the carbonyl source and 4-(dimethylamino)pyridine (DMAP) as base. The reaction conditions were optimized with respect to different bases, molar ratio of DMAP/iodine, temperature, time, and CO pressure. Various p-substituted arylamines can be converted into the respective symmetrical and unsymmetrical N,N'-disubstituted ureas in moderate to good yields. The reaction demonstrated broad tolerance of functionality.
- Zhang, Li,Darko, Ampofo K.,Johns, Jennifer I.,McElwee-White, Lisa
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experimental part
p. 6261 - 6268
(2011/12/04)
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- Carbon dioxide as a carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas: Scope and limitations
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Carbon dioxide can be used as a convenient carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas. The transient carbamate anion generated by treating a primary or secondary amine group in basic media can be activated with phosphorylating agents such as Diphenylphosphoryl azide (DPPA) and Diphenyl chlorophosphate (DPPCl) but also with other types of electrophiles such as SOCl2, TsCl, or AcCl. The intramolecular trapping of the activated carbamate by a hydroxyl group leads to the formation of 2-oxazolidinones or 2-oxazinones in good to excellent yields. This methodology was successfully applied to the synthesis of cyclic ureas up to 7-membered rings from the corresponding diamines.
- Paz, Jairo,Perez-Balado, Carlos,Iglesias, Beatriz,Munoz, Luis
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supporting information; experimental part
p. 3037 - 3046
(2010/07/15)
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- Synthesis of carbamates and ureas using Zr(IV)-catalyzed exchange processes
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Equation presented Zirconium(IV)-catalyzed exchange processes have been developed to prepare both carbamates and ureas from dialkyl arbonates and carbamates employing 2-hydroxypyridine (HYP) and 4-methyl-2-hydroxyquinoline (MeHYQ) as catalytic additives, respectively A microwave acceleration effect was observed in Zr(IV)-catalyzed carbamate-urea exchange.
- Han, Chong,Porco Jr., John A.
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p. 1517 - 1520
(2008/02/02)
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- W(CO)6-catalyzed oxidative carbonylation of primary amines to n,n'-disubstituted ureas in single or biphasic solvent systems. Optimization and functional group compatibility studies
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Primary amines undergo carbonylation to N,N'-disubstituted ureas using W(CO)6 as the catalyst, I2 as the oxidant, and CO as the carbonyl source. Preparation of various N,N'-disubstituted ureas from aliphatic primary amines, RNH2 (R = n-Pr, n-Bu, i-Pr, sec-Bu, or t-Bu), was achieved in good to excellent yields. Studies of functional group compatibility using a series of substituted benzylamines demonstrated broad tolerance of functionality during the carbonylation reaction. Preparation of various N,N'-disubstituted ureas from substituted benzylamines, R-C6H4CH2NH2 (R = H, p-OCH3, p-CO2H, p-CO2Et, p-CH2OH, p-SCH3, p-vinyl, p-Cl, p-Br, m-I, p-NH2, p-NO2, or p-CN), was achieved in good yields. For many substituted benzylamines, yields of ureas were higher when a two-phase CH2Cl2/H2O solvent system was used.
- McCusker, Jennifer E.,Main, A. Denise,Johnson, Kirsten S.,Grasso, Cara A.,McElwee-White, Lisa
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p. 5216 - 5222
(2007/10/03)
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- A NEW SYNTHESIS OF HETEROCYCLES VIA CARBONILATION OF AMINES WITH CARBON MONOXIDE IN THE PRESENCE OF SELENIUM
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Amines which contain a second functional group in the appropriate position react with carbon monoxide in the presence of selenium to form heterocyclic derivatives in which carbon monoxide is incorporated.For instance, diamines, aminoalcohols, and their related compounds undergo carbonylation to give cyclic ureas, urethanes and the corresponding carbonylated compounds.For diamines and amino alcohols with more than two carbon atoms between the functional groups, intermolecular carbonylative coupling takes place competing with the intramolecular reaction.High selectivity has been attained under specified reaction conditions.Anilines having cyano or acetyl groups on the ortho position afford new classes of selenium-containing heterocycles.In these reactions, carbamoselenoate has been suggested as the common key intermediate.
- Yoshida, Tohru,Kambe, Nobuaki,Ogawa, Akiya,Sonoda, Noboru
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p. 137 - 148
(2007/10/02)
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- A New Synthesis of Cyclic Ureas, Cyclic Urethanes, and a Quinazolinedione. Selenium-Assisted Carbonylation of Aromatic Amines with Carbon Monoxide
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Five-, six-, and seven-membered cyclic ureas were synthesized in excellent yields from various aromatic diamines by reaction with carbon monoxide and a stoichiometric or excess amount of selenium in the presence of an oxidizing agent such as oxygen or dimethyl sulfoxide producing selectively the five- and six-membered cyclic ureas.In the case of 2-(2-aminoethyl)aniline under the catalytic conditions, intra- and intermolecular carbonylation competed resulting in the formation of a mixture of the seven-membered cyclic urea, 1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one and the acyclic urea, 1,3-bisurea.The distribution ratio of these two products varied depending on the reaction conditions, but selective formation of the cyclic urea was attained only when a stoichiometric or excess amount of selenium was used.In addition to the above diamino compounds, 2-carbamoylaniline, 2-amino-3-pyridinol, and 2-(hydroxymethyl)-aniline also underwent similar carbonylation to give 2,4(1H,3H)-quinazolinedione, oxazolopyridin-2-(3H)-one, and 1,4-dihydro-2H-3,1-benzoxazin-2-one, respectively.
- Yoshida, Tohru,Kambe, Nobuaki,Murai, Shinji,Sonoda, Noboru
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p. 1793 - 1800
(2007/10/02)
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- A NEW SYNTHESIS OF CYCLIC UREAS FROM AROMATIC DIAMINES BY SELENIUM-ASSISTED CARBONYLATION WITH CARBON MONOXIDE
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Aromatic cyclic ureas have been synthesized in good yields from o-amino or o-aminoalkyl substituted aromatic amines by the reaction with carbon monoxide using selenium.
- Yoshida, Tohru,Kambe, Nobuaki,Murai, Shinji,Sonoda, Noboru
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p. 3037 - 3040
(2007/10/02)
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