- Direct palladium-catalyzed ortho-arylation of benzylamines
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Unsubstituted benzylamines and N-methylbenzylamine can be ortho-arylated under palladium catalysis at 130 °C. The reactions require the presence of trifluoroacetic acid and silver acetate.
- Lazareva, Anna,Daugulis, Olafs
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Read Online
- AMINE-BORANES AS BIFUNCTIONAL REAGENTS FOR DIRECT AMIDATION OF CARBOXYLIC ACIDS
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The present invention generally relates to a process for selective and direct activation and subsequent amidation of aliphatic and aromatic carboxylic acids to afford an amide R3CONR1R2. That the process is capable of delivering gaseous or low-boiling point amines provides a major advantage over existing methodologies, which involves an intermediate of triacyloxyborane-amine complex [(R3CO2)3—B—NHR1R2]. This procedure readily produces primary, secondary, and tertiary amides, and is compatible with the chirality of the acid and amine involved. The preparation of known pharmaceutical molecules and intermediates has also been demonstrated.
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Paragraph 0008-0009; 0063-0064
(2022/03/04)
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- A CO2-Catalyzed Transamidation Reaction
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Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO2as a traceless catalyst: in the presence of catalytic amounts of CO2, transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular,N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO2-catalyzed transamidation versus a N2atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO2, which was supported by DFT calculations. We attributed the positive effect of CO2in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO2
- Yang, Yang,Liu, Jian,Kamounah, Fadhil S.,Ciancaleoni, Gianluca,Lee, Ji-Woong
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p. 16867 - 16881
(2021/11/18)
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- Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy
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Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.
- Zhao, Chenxi,Tang, Chu,Li, Changhao,Ning, Wentao,Hu, Zhiye,Xin, Lilan,Zhou, Hai-Bing,Huang, Jian
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- Amine-boranes as Dual-Purpose Reagents for Direct Amidation of Carboxylic Acids
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Amine-boranes serve as dual-purpose reagents for direct amidation, activating aliphatic and aromatic carboxylic acids and, subsequently, delivering amines to provide the corresponding amides in up to 99% yields. Delivery of gaseous or low-boiling amines as their borane complexes provides a major advantage over existing methodologies. Utilizing amine-boranes containing borane incompatible functionalities allows for the preparation of functionalized amides. An intermolecular mechanism proceeding through a triacyloxyborane-amine complex is proposed.
- Choudhary, Shivani,Hamann, Henry J.,Ramachandran, P. Veeraraghavan
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- Graphene oxide: A convenient metal-free carbocatalyst for facilitating amidation of esters with amines
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Herein, we report a graphene oxide (GO) catalyzed condensation of non-activated esters and amines, that can enable diverse amides to be synthesized from abundant ethyl esters forming only volatile alcohol as a by-product. GO accelerates ester to amide conversion in the absence of any additives, unlike other catalysts. A wide range of ester and amine substrates are screened to yield the respective amides in good to excellent yields. The improved catalytic activity can be ascribed to the oxygenated functionalities present on the graphene oxide surface which forms H-bonding with the reactants accelerating the reaction. Improved yields and a wide range of functional group tolerance are some of the important features of the developed protocol.
- Patel, Khushbu P.,Gayakwad, Eknath M.,Shankarling, Ganapati S.
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p. 2661 - 2668
(2020/02/20)
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- Direct amidation of non-activated carboxylic acid and amine derivatives catalyzed by TiCp2Cl2
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This paper described a mild and efficient direct amidation of non-activated carboxylic acid and amine derivatives catalyzed by TiCp2Cl2. Arylacetic acid derivatives reacted with different amines to afford the corresponding amides in good to excellent yield except of aniline. Aryl formic acids failed to react with aniline but smoothly reacted with aliphatic amines and benzylamine in moderate to good yield, fatty acids reacting with benzyl and aliphatic amines give amides in good to excellent yield. Chiral amino acids derivatives were transformed into amides without racemization in moderate yield. The possible mechanism of direct amidation catalyzed by TiCp2Cl2 was discussed. This catalytic method is very suitable for the amidation of low sterically hindered arylacetic acid, fatty acids with different low sterically hindered amines except aniline, as well as the amidation of aryl formic acid with benzyl and aliphatic amines.
- Wang, Hui,Dong, Wei,Hou, Zhipeng,Cheng, Lidan,Li, Xiufen,Huang, Longjiang
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- Carbon-Carbon Bond Formation of Trifluoroacetyl Amides with Grignard Reagents via C(O)-CF3 Bond Cleavage
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The reaction of trifluoroacetyl amides with Grignard reagent for the substitution of CF3 group with various alkyl or aryl groups is described. A variety of aryl, quinolin-8-yl, and (hetero)alkyl functional groups as well as F, Cl, and Br atoms are well tolerated. These moisture-stable and easily available trifluoroacetyl amides can be conveniently obtained and used as new versatile precursors for isocyanates. The control experiments show that the reaction proceeds via an isocyanate intermediate and/or alkoxide/amide dual anionic intermediate.
- Zhu, Longzhi,Le, Liyuan,Yan, Mingpan,Au, Chak-Tong,Qiu, Renhua,Kambe, Nobuaki
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p. 5635 - 5644
(2019/05/10)
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- 1,1-Diacyloxy-1-phenylmethanes as versatile N-acylating agents for amines
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1,1-Diacyloxy-1-phenylmethanes and 1-pivaloxy-1-acyloxy-1-phenylmethanes have been used as bench stable N-acylating reagents for primary and secondary amines and anilines under solvent-free conditions to afford their corresponding amides in good yield.
- Chapman, Robert. S.L.,Tibbetts, Joshua. D.,Bull, Steven. D.
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p. 5330 - 5339
(2018/06/15)
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- Acetic acid as a catalyst for the N-acylation of amines using esters as the acyl source
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We report a cheap and simple method for the acetylation of a variety of amines using catalytic acetic acid and either ethyl acetate or butyl acetate as the acyl source. Catalyst loadings as low as 10 mol% afforded acetamide products in excellent yields at temperatures ranging from 80-120 °C. The methodology can also be successfully applied for the synthesis of a broad range of other amides, including the formation of formamides at 20 °C.
- Sanz Sharley, Daniel D.,Williams, Jonathan M. J.
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supporting information
p. 2020 - 2023
(2017/02/15)
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- meta-Selective C?H Borylation of Benzylamine-, Phenethylamine-, and Phenylpropylamine-Derived Amides Enabled by a Single Anionic Ligand
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Selective functionalization at the meta position of arenes remains a significant challenge. In this work, we demonstrate that a single anionic bipyridine ligand bearing a remote sulfonate group enables selective iridium-catalyzed borylation of a range of common amine-containing aromatic molecules at the arene meta position. We propose that this selectivity is the result of a key hydrogen bonding interaction between the substrate and catalyst. The scope of this meta-selective borylation is demonstrated on amides derived from benzylamines, phenethylamines and phenylpropylamines; amine-containing building blocks of great utility in many applications.
- Davis, Holly J.,Genov, Georgi R.,Phipps, Robert J.
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supporting information
p. 13351 - 13355
(2017/10/07)
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- Catalytic reduction of amides to amines by electrophilic phosphonium cations via FLP hydrosilylation
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A catalytic methodology for the conversion of amides to amines is reported. Of the 25 examples described, 14 examples involve the reduction of N-trifluoroacetamides to the corresponding trifluoroethylamines. These reductions are achieved by catalytic hydrosilylation of the amide mediated by an electrophilic phosphonium cation (EPC) catalyst.
- Augurusa, Alessandra,Mehta, Meera,Perez, Manuel,Zhu, Jiangtao,Stephan, Douglas W.
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supporting information
p. 12195 - 12198
(2016/10/21)
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- Direct amidation of carboxylic acids with amines under microwave irradiation using silica gel as a solid support
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A highly improved and green methodology for the direct amidation of carboxylic acids with amines using silica gel as a solid support and catalyst is described. The scope of this method is exemplified by the use of several aliphatic, aromatic, unsaturated and fatty acids. The reaction is also applied to different primary and secondary amines. Typically, the amines should be aliphatic, but aromatic amines can be used as well, though with lower yields. Several experiments to illustrate the selectivity of this methodology were also carried out with several more functionalized acids and amines. This approach is a substantial improvement over other previously described methods in amide synthesis.
- Ojeda-Porras, Andrea,Hernández-Santana, Alejandra,Gamba-Sánchez, Diego
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supporting information
p. 3157 - 3163
(2015/05/27)
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- Hexamethyldisilazane as an acylation generator for perfluorocarboxylic acids in quantitative derivatization of primary phenylalkyl amines confirmed by GC/MS and computations
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A novel, selective acylation of primary phenylalkyl amines (PPAAs) using hexamethyldisilazane (HMDS) and perfluorocarboxylic acids (PFCAs) is noted. Couples, like HMDS and trifluoroacetic acid, HMDS and pentafluoropropionic acid, or HMDS and heptafluorobutyric acid trigger PPAAs' quantitative acylation. Processes' selectivity was characterized by applying all couples to derivatize benzyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl amines, and their relevant substituted versions. Aliphatic amines were unreactive. Identification, quantification, proportionality, and stoichiometry in derivatization processes were determined by gas chromatography/mass spectrometry. Reaction conditions were optimized depending on reagents' molar ratios, solvents, and temperatures applied. The new acylation method, in comparison to the traditional ones, obtained with trifluoroacetic anhydride, heptafluorobutyric anhydride, and N-methyl-bis(trifluoroacetamide), offers numerous advantages. Derivatives, provided by couples, can be directly injected onto the column, avoiding loss of species, saving time, work, and cost in the preparation process. Due to traditional reagents' excess evaporation by nitrogen drying, the loss of trifluoroacylated species proved to be 65% or less. Regarding heptafluorobutyryl species, their losses varied between 25% and 5%. Unified huge responses, obtained with the HMDS and PFCA couples are attributable to their direct injection onto the column and to fragments sourced from the molecular ions and from their self-chemical ionization ([M]?+, [M+147]+, i.e., [M+(CH3)2-Si=O-Si-(CH3)3]+). The reaction mechanism, due to the HMDS symmetrical structure, acting HMDS as acylation generator for PFCAs, was confirmed by density functional theory (DFT) computation.
- Molnr, Borbla,Csmpai, Antal,Molnr-Perl, Ibolya
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p. 848 - 852
(2015/02/19)
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- Quantitative Silylation Speciations of Primary Phenylalkyl Amines, Including Amphetamine and 3,4-Methylenedioxyamphetamine Prior to Their Analysis by GC/MS
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A novel, quantitative trimethylsilylation approach derivatizing 11 primary phenylalkyl amines (PPAAs), including amphetamine (A) and 3,4-methylenedioxyamphetamine (MDA), was noted. Triggering the fully derivatized ditrimethylsilyl (diTMS) species with the N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA) reagent, a new principle was recognized followed by GC/MS. In the course of method optimization, the complementary impact of solvents (acetonitrile, ACN; ethyl acetate, ETAC; pyridine, PYR) and catalysts (trimethylchlorosilane, TMCS; trimethyliodosilane, TMIS) was studied: the role of solvent and catalyst proved to be equally crucial. Optimum, proportional, huge responses were obtained with the MSTFA/PYR = 2/1-9/1 (v/v) reagent applying catalysts; A and MDA needed the TMIS, while the rest of PPAAs provided the diTMS products also with TMCS. Similar to derivatives generated with hexamethyldisilazane and perfluorocarboxylic acid (HMDS and PFCA) (Molnár et al. Anal. Chem. 2015, 87, 848'852), the fully silylated PPAAs offer several advantages. Both of our methods save time and cost by allowing for direct injection of analytes into the column; this is in stark contrast with the requirement to evaporate acid anhydrides by nitrogen prior to their injection. Efficiences of the novel catalyzed trimethylsilylation (MSTFA) and our recently introduced (now, for A and MDA extended) acylation principle were contrasted. Catalyzed trimethylsilylation led to diTMS derivatives resulting in on average a 1.7 times larger response compared to the corresponding acylated species. Catalyzed trimethylsilylation of PPAAs, A, and MDA were characterized with retention, mass fragmentation, and analytical performance properties (R2, LOQ values). The practical utility of ditrimethylsilyation was shown by analyzing A in urine and mescaline (MSC) in cactus samples.
- Molnár, Borbála,Fodor, Blanka,Boldizsár, Imre,Molnár-Perl, Ibolya
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p. 10188 - 10192
(2015/11/09)
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- Steric and Electronic Effects in the Synthesis and Regioselective Hydrolysis of Unsymmetrical Imides
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The AgI-promoted coupling reaction of thioamides and carboxylic acids is shown to be a useful method for the generation of unsymmetrical imides. The reaction proceeds efficiently with unhindered and electron-rich or neutral coupling partners, but not with hindered thioamides (such as thiopivalamides) or electron deficient thioamides (such as trifluorothioacetamides). Intriguingly, thioformamides are also ineffective coupling partners, despite having minimal steric or electronic influence. Hindered carboxylic acid coupling partners (such as pivalic acid) are tolerated, but electron deficient acids, such as trifluoroacetic acid, are ineffective coupling partners. Furthermore, an interplay of both steric and electronic effects is observed in the subsequent hydrolysis of unsymmetrical imides. Imides with a dimethoxybenzoyl group give high regioselectivity upon hydrolysis, favouring cleavage of the distal acyl group. Imides with a p-nitrobenzoyl or pivaloyl group give reversed selectivity, favouring cleavage of the proximal acyl group.
- Shang, Jing,Pourvali, Aysa,Cochrane, James R.,Hutton, Craig A.
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p. 1854 - 1858
(2015/12/26)
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- Benzoic acid-catalyzed transamidation reactions of carboxamides, phthalimide, ureas and thioamide with amines
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An efficient and simple method for the transamidation of carboxamides, phthalimide, ureas and thioamide with amines catalyzed by commercially available benzoic acid under metal-free conditions is described. Furthermore, to the best of our knowledge, this is the first report about the transamidation of an aromatic thioamide with amines.
- Wu, Ji-Wei,Wu, Ya-Dong,Dai, Jian-Jun,Xu, Hua-Jian
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supporting information
p. 2429 - 2436
(2014/09/30)
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- Transition metal-free intermolecular a-C-H amination of ethers at room temperature
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We describe a new method for the intermolecular amination of the α-C-H bonds of ethers. A hypervalent iodine reagent was used as oxidant to enable the amination of cyclic and acyclic alkyl ethers with a wide range of amides, imides, and amines. The amination occurred at room temperature and without a transition metal catalyst. The method could be used to synthesize the anti-cancer prodrug Tegafur and its analogues.
- Buslov, Ivan,Hu, Xile
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supporting information
p. 3325 - 3330
(2015/02/02)
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- Direct synthesis of amides from carboxylic acids and amines using B(OCH2CF3)3
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B(OCH2CF3)3, prepared from readily available B2O3 and 2,2,2-trifluoroethanol, is as an effective reagent for the direct amidation of a variety of carboxylic acids with a broad range of amines. In most cases, the amide products can be purified by a simple filtration procedure using commercially available resins, with no need for aqueous workup or chromatography. The amidation of N-protected amino acids with both primary and secondary amines proceeds effectively, with very low levels of racemization. B(OCH2CF3)3 can also be used for the formylation of a range of amines in good to excellent yield, via transamidation of dimethylformamide.
- Lanigan, Rachel M.,Starkov, Pavel,Sheppard, Tom D.
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p. 4512 - 4523
(2013/06/05)
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- Direct amide coupling of non-activated carboxylic acids and amines catalysed by zirconium(IV) chloride
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Amidst the green: A green, mild and effective protocol for the direct formation of secondary and tertiary amides from non-activated carboxylic acids and amines in good to excellent yields by employing ZrCl4 as the catalyst is presented (see scheme). The amide coupling protocol proved to be suitable for scaled up syntheses, and the mild reaction conditions conserve the enantiopurity of chiral starting materials. Copyright
- Lundberg, Helena,Tinnis, Fredrik,Adolfsson, Hans
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supporting information; experimental part
p. 3822 - 3826
(2012/05/20)
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- Titanium(IV) isopropoxide as an efficient catalyst for direct amidation of nonactivated carboxylic acids
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Secondary and tertiary amides are formed in high yields, in an efficient and environmentally benign titanium(IV) isopropoxide catalyzed direct amidation of carboxylic acids with primary and secondary amines. Georg Thieme Verlag Stuttgart ? New York.
- Lundberg, Helena,Tinnis, Fredrik,Adolfsson, Hans
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supporting information
p. 2201 - 2204
(2012/10/30)
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- Pd-catalyzed asymmetric synthesis of N-allenyl amides and their Au-catalyzed cycloisomerizative hydroalkylation: A new route toward enantioenriched pyrrolidones
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Palladium to make them, gold to cyclize them! Gold-catalyzed cycloisomerizative hydroalkylation of N-allenyl amides affords regioselectively 4-vinyl-γ-lactams. This transformation is stereospecific and takes place with a total axis-to-center chirality tra
- Boutier, Audrey,Kammerer-Pentier, Claire,Krause, Norbert,Prestat, Guillaume,Poli, Giovanni
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supporting information; experimental part
p. 3840 - 3844
(2012/06/15)
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- Mechanism of the acid-mediated thermal fragmentation of 5-spirocyclobutane-isoxazolidines
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Protonation at the nitrogen of 5-spirocyclopropane-isoxazolidines induces clean thermal rearrangement/fragmentation to β-lactams and ethylene. Under the same conditions, homologous 5-spirocyclobutane-isoxazolidines undergo unselective fragmentation to give cyclobutyl derivatives through a completely different mechanism. Experimental data and DFT calculations show that the process is initiated with less-favored protonation at the isoxazolidine oxygen rather than nitrogen. Highly energetic O-protonated isoxazolidines undergo N-O cleavage with concomitant endo-or exocyclic deprotonation to give iminium ions that, in the presence of trifluoroacetate, evolve into 2-(1-hydroxycyclobutyl) ethanones and N-[2-(1-hydroxycyclobutyl)ethyl]trifluoroacetamides, respectively. DFT data validate protonation at oxygen of 5-spirocyclobutane-isoxazolidines, which requires higher energy than protonation at nitrogen, but can trigger the proposed process without any energy barrier. The N-protonated derivatives could rearrange to give oxazaspirooctane, with enlargement of the spirocyclobutane ring, but this process, owing to its high energy barrier, cannot compete with the reaction channel promoted by oxygen protonation and, in fact, is not experimentally observed. Being independent of the presence of a strained spirofused ring, acid-catalyzed fragmentation was also demonstrated to occur in normal isoxazolidines, such as those derived from cycloaddition of C-Ph-N-Me-nitrone to norbornene, suggesting that isoxazolidines, widely used in organic synthesis, should not be heated in the presence of protic acids.
- Cordero, Franca M.,Vurchio, Carolina,Brandi, Alberto,Gandolfi, Remo
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experimental part
p. 5608 - 5616
(2011/11/29)
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- Convenient one-pot synthesis of N-substituted 3-trifluoroacetyl pyrroles
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A new one-pot strategy for the synthesis of a series of new N-substituted 3-trifluoroacetyl pyrroles is presented. These compounds were obtained by the reaction of 3-trifluoroacetyl-4,5-dihydrofuran with primary amines, which generated 1,1,1-trifluoro-3-(2-hydroxyethyl)-4-alkylaminobut-3-en-2-one intermediates. In most cases these intermediates were not stable enough to be isolated. Thus, in the same reaction vessel they were directly submitted to oxidation with PCC (Corey's reagent) to furnish 1,1,1-trifluoro-3-(2-ethanal)-4- alkylaminobut-3-en-2-ones, which under reflux underwent intramolecular cyclization to give the desired N-substituted 3-trifluoroacetyl pyrroles, in moderate yields. All of these pyrroles were tested against pan-susceptible Mycobacterium tuberculosis H37Rv and clinical isolates INH- and RMP-resistant strain and some of these compounds showed significant in vitro antimicrobial activity. Georg Thieme Verlag Stuttgart.
- Zanatta, Nilo,Wouters, Ana D.,Fantinel, Leonardo,Da Silva, Fabio M.,Barichello, Rosemário,Da Silva, Pedro E. A.,Ramos, Daniela F.,Bonacorso, Helio G.,Martins, Marcos A. P.
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experimental part
p. 755 - 758
(2009/07/18)
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- A facile and convenient synthetic method for 2-bis(trifluoroacetyl)methylene- and 2-trifluoro-acetylmethylene-2,3-dihydro-3-methylthiazoles
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2,3-Dimethylthiazolium iodides (1) reacted easily with trifluoroacetic anhydride in the presence of pyridine to give 2-bis(trifluoroacetyl)methylene-2,3-dihydro-3-methylthiazoles (2) in excellent yields. Deacylation of 2 proceeded readily in moderate to high yields by acid catalyst such as silica gel and aqueous hydrochloric acid to afford the corresponding 2-trifluoroacetylmethylene-2,3-dihydro-3-methylthiazoles (3), which were smoothly reconverted into diacylated compounds (2) with trifluoroacetic anhydride. The highly poralized structure of 2 was also briefly discussed.
- Ota, Norio,Okada, Etsuji,Kamitori, Yasuhiro,Shibata, Dai,Médebiellec, Maurice
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p. 721 - 730
(2008/09/18)
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- Direct ortho iodination of β- and γ-aryl alkylamine derivatives
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Two in one! A trifluoroacetamide protecting group not only masks an amine functionality, but also mimics peptidyl directing effects as a controlling unit in an efficient ortho iodination of a variety of biologically relevant small molecules (see example). (Chemical Equation Presented).
- Barluenga, Jose,Alvarez-Gutierrez, Julia M.,Ballesteros, Alfredo,Gonzalez, Jose M.
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p. 1281 - 1283
(2008/03/27)
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- Trifluoroacetyl-Activated Nitrogen-Nitrogen Bond Cleavage of Hydrazines by Samarium(II) Iodide
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(Matrix presented) Trifluoroacetyl derivatives of hydrazines undergo clean and efficient reductive cleavage of the N-N bond with Sml2 in the presence of MeOH. After N-trifluoroacetylation, acyl-, aryl-, and alkyl-substituted hydrazines are redu
- Ding, Hui,Friestad, Gregory K.
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p. 637 - 640
(2007/10/03)
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- Biomimetic reductive amination of perfluoroalkylcarboxylic acids to α,α-dihydroperfluoroalkylamines
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The first general method for the reducing reagent-free, biomimetic transformation of perfluorocarboxylic acids to the α,α-dihydroperfluoroalkyl amines is reported. High chemical yields and simplicity of the experimental procedure render this method immediately useful and synthetically superior to the conventional approaches relying on application of reducing reagents.
- Soloshonok, Vadim A,Ohkura, Hironari,Uneyama, Kenji
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p. 5449 - 5452
(2007/10/03)
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- A convenient synthesis of Trifluoroacetamides from sodium trifluoroacetate and amines
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Trifluoroacetamides were prepared readily by reaction of sodium trifluoroacetate with triphenylphosphine di-iodide and amines consecutively under mild conditions with good yields.
- Zhou, Qi-Zhong,Chen, Zhen-Chu
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p. 3189 - 3194
(2007/10/03)
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- Kinetics and mechanism of aminolysis of aliphatic esters in aprotic solvents
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Kinetic studies were carried out on the aminolysis reactions of substituted aliphatic esters in a variety of aprotic solvents. The reaction rate is strongly affected by inductive and steric effects of substituents in the acyl group, rising more than 104-fold from cyanoacetate to trifluoroacetate. The quantitative treatment of solvent effects revealed a rate decrease by the polarity and π-basicity of the solvents, and also an accelerating effect of the polarizability of solvents. Cyclic transition states were assumed for both the first and second-order (in amine) reactions. Copyright
- Talvik, Agu-Tonis,Tuulmets, Ants,Vaino, Evi
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p. 747 - 750
(2007/10/03)
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- Reductive cleavage of N-O bonds in hydroxylamines and hydroxamic acid derivatives using samarium diiodide
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An efficient process for the reductive cleavage of N-O bonds using samarium diiodide is detailed for a variety of structural types to define the scope and limitations of the method. The reduction is shown to be compatible with base sensitive substrates such as trifluoroacetamide derivatives, which cannot be reduced satisfactorily using aluminum amalgam or sodium amalgam. Direct quenching of the reduction mixture with acylating agents is demonstrated to provide high yields of protected amines in a one-pot process from the N-O derivatives.
- Keck, Gary E.,Wager, Travis T.,McHardy, Stanton F.
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p. 11755 - 11772
(2007/10/03)
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- Microwave-promoted trifluoroacetylation of amines with TiO(CF3CO2)2
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Conversion of amines to their corresponding trifluoroacetamides was performed with TiO(CF3CO2)2 in a conventional microwave oven under solvent-free conditions in excellent yields.
- Iranpoor, Nasser,Zeynizadeh, Behzad
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p. 124 - 125
(2007/10/03)
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- Synthesis and reactions of 2-hydroxy-5,5-dimethyl- and 2-hydroxy-5,5-pentamethylene-2-trifluoromethyltetrahydro-4-pyranones with N-nucleophiles
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Condensation of 4-hydroxy-3,3-dimethyl- and 4-hydroxy-3,3-pentamethylenebutan-2-ones with ethyl trifluoroacetate in the presence of LiH in hexane afforded 2-hydroxy-5,5-dimethyl- and 2-hydroxy-5,5-pentamethylene-2-trifluoromethyltetrahydro-4-pyranones, wh
- Sosnovskikh,Mel'nikov,Zaitsev,Bogdanov
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p. 1170 - 1174
(2007/10/03)
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- Ureas in Organic Synthesis. XIII. Reactions of 1,3-Disubstituted Ureas with Acetic Acid Derivatives
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Reaction of 1,3-disubstituted ureas with the derivatives of acetic acid yields depending on the substrate structure and process conditions either acetamides or N-acetylureas. Addition of urea inhibits N-acylation.
- Shtrykova,Bakibaev
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p. 460 - 463
(2007/10/03)
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- Biomimetic reductive amination of fluoro aldehydes and ketones via [1,3]-proton shift reaction. Scope and limitations
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A systematic study of azomethine-azomethine isomerizations of the N-benzylimines 2, derived from fluorinated aldehydes or ketones and benzylamine, has been made. The results reveal that, in sharp contrast to hydrocarbon analogs, fluorinated imines of 2 in triethylamine solution undergo isomerizations to give the corresponding N-benzylidene derivatives 5 (for 5/2 K > 32) in good isolated yields. The rates of the isomerizations depend on the starting imine structures and increase in the following order: aryl perfluoroalkyl ketimine 2m, per(poly)fluoroalkyl aldimine 2a,d-g, perfluoroaryl aldimine 2h, alkyl perfluoroalkyl ketimine 2i,j. The presence of chlorine or bromine atoms in the α-position to the C=N double bond of the starting imine favors a dehydrohalogenation reaction, giving rise to unsaturated products 6-9. The azomethine-azomethine isomerization was studied and proven to proceed essentially (>98%) intramolecularly with isotope exchange experiments. High chemical yields, the simplicity of the experimental procedure, and the low cost of all reagents employed make this biomimetic transamination of fluorocarbonyl compounds a practical method for preparing fluorine-containing amines of biological interest.
- Ono, Taizo,Kukhar, Valery P.,Soloshonok, Vadim A.
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p. 6563 - 6569
(2007/10/03)
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- Reductive cleavage of N - O bonds in hydroxylamine and hydroxamic acid derivatives using Sml2/THF
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The title reaction affords a general method for the reductive cleavage of N - O bonds, and is successful in some cases where established methods fail.
- Keck, Gary E.,McHardy, Stanton F.,Wager, Travis T.
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p. 7419 - 7422
(2007/10/02)
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- FLUORINE-CONTAINING AMINO ACIDS. V. IMINES OF TRIFLUOROPYRUVIC ACID IN THE SYNTHESIS OF N-SUBSTITUTED TRIFLUOROALANINES
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N-Substituted trifluoroalanine methyl esters were obtained by the reduction of the corresponding imines of trifluoropyruvic acid with zinc in acetic acid.The N-butyl- and N-(1-phenylethyl)imines undergo a -proton shift under the influence of bases with the formation of trifluoroalanine derivatives.It was found that the N-(1-phenylethyl)imine of tetrafluoropyruvic acid is formed directly from the corresponding amine and methyl trifluoropyruvate under conditions with azeotropic distillation of the water with toluene in the presence of acidic catalysis.
- Soloshonok, V. A.,Yagupol'skii, Yu. L.,Kukhar, V. P.
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p. 1478 - 1482
(2007/10/02)
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- A CONVENIENT SYNTHESIS OF N-ALKYL AND N,N-DIALKYLTRIFLUOROACETAMIDES IN A SOLID-LIQUID TWO-PHASE SYSTEM IN THE PRESENCE OF PHASE-TRANSFER CATALYSTS
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Trifluoroacetamide is easily monoalkylated in a K2CO3-organic solvent solid-liquid two-phase system affording in good to excellent yields N-alkyltrifluoroacetamides.Under the same conditions, the latter, in turn, ract with alkylating agents giving N,N-dialkyltrifluoroacetamides in high yields.
- Landini, Dario,Penso, Michele
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p. 791 - 800
(2007/10/02)
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- THIONO COMPOUNDS. 7. OXIDATION OF THIOAMIDES IN RELATION TO ADVERSE BIOLOGICAL EFFECTS
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Thioacetamide, thioacetamide S-oxide (1), and thiopivalamide S-oxide (8) were oxidized with H2O2 in H2(18)O to generate the corresponding amides with at least 50percent 18O incorporation; hydrolysis of the S-oxides to the amides or 18O exchange with the amides occurs much more slowly.When 1 and trifluorothioacetamide (6) were oxidized with three and four equivalents of H2O2, respectively, in the presence of benzylamine, N-acetylbenzylamine (5) and N-benzyltrifluoroacetamide (7) were isolated in respective yields of 17percent and 37percent.These results are interpreted as evidence for an oxidative desulfurization mechanism involving nucleophilic attack at the carbon atom of an S,S-dioxide or trioxide intermediate as the major pathway; a minor pathway may involve the intermediacy of an oxathiirane S-oxide (3) or dioxide (4) species.Understanding is added to the behavior of S-oxides in aqueous solution, as well as to thermal stability in deuterochloroform.Also reported are studies of the preparation and properties of some N,N-dialkyl derivatives of 8, of reduction of 1 with NADH or NADPH, and of generation and trapping of species related to sulfoxylate ion.
- Hillhouse, John H.,Blair, Ian A.,Field, Lamar
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p. 169 - 184
(2007/10/02)
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- Design of Inhibitors from the Three-Dimensional Structure of Alcohol Dehydrogenase. Chemical Synthesis and Enzymatic Properties
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Inhibitors of liver alcohol dehydrogenase were designed from the three-dimensional structure of the enzyme.The ligand to the catalytic zinc ion is an amide group or, better, a formamide group.With the latter function, a hydrogen bond between the NH group and the hydroxyl group of Ser-48 may be formed.The hydrophobic substrate binding site brings structural restraints. α-ω bifunctional molecules show good inhibitory properties possibly due to the interactions with polar residues at the entrance of the substrate binding site.
- Freudenreich, Charles,Samama, Jean-Pierre,Biellmann, Jean-Francois
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p. 3344 - 3353
(2007/10/02)
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