- Direct Amidation of Esters by Ball Milling**
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The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
- Barreteau, Fabien,Battilocchio, Claudio,Browne, Duncan L.,Godineau, Edouard,Leitch, Jamie A.,Nicholson, William I.,Payne, Riley,Priestley, Ian
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supporting information
p. 21868 - 21874
(2021/09/02)
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- Carbene insertion into N-H bonds with size-selectivity induced by a microporous ruthenium-porphyrin metal-organic framework
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A stable and porous porphyrinic metal-organic framework, Ru-PMOF-1(Hf), has been prepared through the self-assembly of [5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato](monocarbonyl)ruthenium (Ru(TCPP)(CO)) and HfCl4. Single-crystal X-ray diff
- Chen, Lianfen,Cui, Hao,Wang, Yanhu,Liang, Xiang,Zhang, Li,Su, Cheng-Yong
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supporting information
p. 3940 - 3946
(2018/03/21)
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- Dual role of Cu2O nanocubes as templates and networking catalysts for hollow and microporous Fe-porphyrin networks
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Cu2O nanocubes were used for the synthesis of hollow and microporous Fe porphyrin networks (H-MFePN). In this synthesis, Cu2O nanocubes performed not only as networking catalysts but also as shape controlling templates. MFePN were formed on the surface of the Cu2O nanocubes through azide-alkyne cycloaddition of tetrakis(4-ethynylphenyl) Fe-porphyrin with 1,4-diazidobenzene. H-MFePN showed excellent catalytic activities in carbene insertion into N-H bonds, maintaining their activities during five recycle tests.
- Kang, Daye,Ko, Ju Hong,Choi, Jaewon,Cho, Kyoungil,Lee, Sang Moon,Kim, Hae Jin,Ko, Yoon-Joo,Park, Kang Hyun,Son, Seung Uk
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supporting information
p. 2598 - 2601
(2017/03/09)
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- Synthesis of carbamoylacetates from α-iodoacetate, CO, and amines under Pd/light combined conditions
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We developed a novel synthetic method of carbamoylacetates from -iodoacetate, carbon monoxide, and amines under photoirradiation conditions in the presence of a Pd catalyst. This reaction likely proceeds via interplay of radical and organopalladium species. Georg Thieme Verlag Stuttgart · New York.
- Sumino, Shuhei,Fusano, Akira,Fukuyama, Takahide,Ryu, Ilhyong
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experimental part
p. 1331 - 1334
(2012/07/13)
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- N,N′-Dialkylaminoalkylcarbonyl (DAAC) prodrugs and aminoalkylcarbonyl (AAC) prodrugs of 4-hydroxyacetanilide and naltrexone with improved skin permeation properties
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N,N′-Dialkylaminoalkylcarbonyl (DAAC) and aminoalkylcarbonyl (AAC) prodrugs of phenolic drugs acetaminophen (APAP) and naltrexone (NTX) are reported. The effects of incorporation of a basic amine group into the promoiety of an acyl prodrug of a phenolic drug on its skin permeation properties are also presented. DAAC-APAP prodrugs were synthesized via a three-step procedure starting with haloalkylcarbonyl esters which were reacted with five different amines: dimethylamine, diethylamine, dipropylamine, morpholine, and piperidine. The spacing between the amino group and the carbonyl group of the acyl group was 1-3 CH2. After the hydrolysis of the ester, the carboxylic acid product was subsequently coupled with the parent drug via a dicyclohexyl carbodiimide (DCC) mediated coupling to yield the DAAC-APAP-HCl prodrugs in excellent yields. The AAC prodrugs were synthesized using commercially available Boc-protected amino acids using DCC or EDCI as coupling agents. The yields of the prodrugs synthesized using these two different methods have been compared. Half-lives (t1/2) of a few members of the DAAC and AAC series were measured in buffer (pH 6.0, 20 mM). The members evaluated in hydrolysis experiments exhibit a t1/2 range of 15-113 min. Among AAC-APAP prodrugs, the isopropyl group in valinate-APAP-HCl exerted a steric effect that increased the t1/2 value for this prodrug compared to alaninate-APAP-HCl or prolinate-APAP-HCl. The 2-morpholinylacetate-APAP prodrug was able to achieve twice the flux of APAP in in vitro diffusion cell experiments through hairless mouse skin.
- Devarajan-Ketha,Sloan
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scheme or table
p. 4078 - 4082
(2011/08/06)
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- A RuII-N-heterocyclic carbene (NHC) complex from metal-metal singly bonded diruthenium(I) precursor: Synthesis, structure and catalytic evaluation
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A mononuclear Ru(II)-N-heterocyclic carbene (NHC) complex [Ru II(CO)2(κ2C,N-BIN)(H2O)Br] [OTf] (OTf = trifluoromethane sulphonate) (1) has been synthesized in high-yield by the oxidative cleavage of the metal-metal singly-bonded diruthenium(I) precursor [Ru2(CO)4(CH3CN)6(OTf) 2] with 1,8-naphthyridine functionalized NHC precursor 1-benzyl-3-(5,7-dimethyl-1,8-naphthyrid-2-yl)imidazolium bromide (BIN·HBr) at room temperature. Compound 1 catalyzes transfer hydrogenation of ketones to alcohols, and carbene-transfer from ethyl diazoacetate to a variety of substrates. It is shown to be an excellent catalyst for the insertion of carbene into the O-H and N-H bonds of alcohols and amines.
- Sinha, Arup,Daw, Prosenjit,Rahaman, S.M. Wahidur,Saha, Biswajit,Bera, Jitendra K.
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experimental part
p. 1248 - 1257
(2011/04/22)
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- Synthesis of new copper(i) complexes with tris(2-pyridyl) ligands. Applications to carbene and nitrene transfer reactions
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New copper(i) complexes with tris(2-pyridyl)methane (TPC), tris(2-pyridyl)methoxymethane (TPM) and tris(2-pyridyl)amine (TPN) ligands have been synthesized and characterized, including structural determinations by X-ray diffraction of some examples. Their activity as catalysts in carbene and nitrene transfer reactions was studied.
- Perez, Julio,Morales, Dolores,Garcia-Escudero, Luis A.,Martinez-Garcia, Hector,Miguel, Daniel,Bernad, Pablo
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scheme or table
p. 375 - 382
(2009/04/14)
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- Catalytic insertion of diazo compounds into N-H bonds: The copper alternative
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The complexes TpXCu (TpX = homoscorpionate) catalyse the insertion of diazo compounds into nitrogen-hydrogen bonds of amines and amides, under very mild conditions, with quantitative yields being obtained with equimolar ratios of reactants.
- Morilla, M. Esther,Diaz-Requejo, M. Mar,Belderrain, Tomas R.,Nicasio, M. Carmen,Trofimenko, Swiatoslaw,Perez, Pedro J.
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p. 2998 - 2999
(2007/10/03)
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- Efficient and Highly Selective Copper(II) Transport across a Bulk Liquid Chloroform Membrane Mediated by Lipophilic Dipeptides
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Several structurally simple N-monoalkylated and -dialkylated dipeptides made of α-amino acids Gly, Phe, and Leu, 1-11, were synthesized and investigated as carriers for the transport of Cu(II), Zn(II), and Ni(II) from an aqueous pH = 5.6 buffer source to a 0.1 M HCl receiving phase across a bulk chloroform membrane. The proton-driven translocation was followed during the process by analyzing the metal ion concentrations in the three phases. The transport efficiency depends on the ease of formation of a neutral complex with Cu(II) (the peptide group and carboxylic acid being deprotonated) at the source-chloroform interface and on that of its disruption by protonation at the receiving phase: the carrier's lipophilicity favors the metal ion uptake and not the release. By modulating the length of the N-alkyl chains and the hydrophobicity of the dipeptide moiety, a quite remarkable transport efficiency was observed for Cu(II), in most cases superior to that of the industrial extractant Kelex 100. Moreover, using L,L- and L,D-N-octyl-PheLeu as carriers, remarkable diastereomeric effects were observed in the rate of uptake and release of Cu(II) ion although the differences mutually compensate in the overall transport rate. Under the conditions used the carriers are much less effective in the translocation of Zn(II) and Ni(II) and their transport efficiency drops dramatically in the presence of Cu(II), the latter being favored by factors of 1.2 × 103 and > 104, respectively. Such very high selectivities depend on the fact that only Cu(II) among other transition metal ions can form neutral complexes at the pH value of the source phase.
- Cleij, Marco C.,Scrimin, Paolo,Tecilla, Paolo,Tonellato, Umberto
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p. 5592 - 5599
(2007/10/03)
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- Insertion of ethyl diazoacetate into N-H and S-H bonds catalyzed by ruthenium porphyrin complexes
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Ruthenium porphyrin complexes catalyze insertion of ethyl diazoacetate into sulfur-hydrogen and nitrogen-hydrogen bonds under mild conditions and with reasonable to very good yields.
- Galardon, Erwan,Le Maux, Paul,Simonneaux, Gerard
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p. 2455 - 2456
(2007/10/03)
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- Substituent Effects on the Strength of C-C-Bonds. IX. Thermolability of 2,3-Di(N,N-dialkylamino)-diethyl-succinates
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The title compounds meso and D,L 3a-c have been prepared from R,R'N-CH2-COOEt (5), R,R'=CH3 (a), C2H5 (b) and i-C3H7 (c), by lithiation followed by oxydation with I2.The thermolysis of (3) above 140 deg C in solution generates the radicals 1, which could be detected by e.s.r.Kinetic measurements are performed in the presence of phenylthiol as a scavenger and the activation parameters are determined. - The steric acceleration of the cleavage reaction is separated using the correlation , whereby the strain values are taken from force field calculations.The obtained strain free barrier to dissociation b = 37.4 kcal/mol is considerably lower than the value for the thermolysis reaction of tetraalkyl ethanes (b=66.2 kcal/mol). The decrease of the activation enthalpy (ΔΔH(excit.) = 35.4 kcal/mol) is mainly caused by stabilisation of 1 compared to sec. alkyl radicals; heats of formation of meso-3a and 5a support this conclusion. Furthermore, the decrease of bond strength in 3 by the two geminal capto-dative substituents exceeds the sum of the effect of one ester group (ΔΔH(excit.)=4 kcal/mol and one amino group (ΔΔH(excit.)=9.5 kcal/mol), drawn from the thermolysis of 1,2-(N,N-Dimethylamino)-1,2-diphenylethane (4)) by about 4 kcal/mol.
- Schulze, Rainer,Beckhaus, Hans-Dieter,Ruechardt, Christoph
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p. 325 - 330
(2007/10/02)
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- Syntheses des alkyl-1 cyclanols fonctionnalises aux positions α, β et γ de la chaine hydrocarbonee
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We have developed a general and versatile synthesis of N,N-dialkylaminoalkyl-, 1-chloroalkyl-, 1-phenoxyalkyl-, 1-thiophenoxyalkyl-, 1-diethoxyalkyl-, and 1-(1,3-dithiolane)alkylcyclanols in good yields by the reaction of α,ω-bis(bromomagnesio)alkanes with the corresponding functionalized carboxylic acid esters.
- Canonne, P.,Belley, M.,Fytas, G.,Plamondon, J.
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p. 168 - 173
(2007/10/02)
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- Silicon Polonovski Reaction. Formation and Synthetic Application of α-Siloxy Amines
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A new and versatile synthetic intermediate, α-siloxy amine was prepared in situ by the base-promoted rearrangement of a siloxyammonium salt obtained by treatment of a tertiary amine N-oxide with trialkylsilyl trifluoromethanesulfonate.The best combination of the base and silylating reagent was found to be methyllithium and t-butyldimethylsilyl trifluoromethanesulfonate.The reactions of α-siloxy amines with acyl halides and haloformates gave the corresponding amides and carbamates in moderate to good yields, respectively.Treatment of α-siloxy amines with acetic acid resulted in a direct dealkylation to free secondary amines.Fluoride induced alkylation of α-siloxy amines using alkyl halides as electrophiles leading to tertiary amines was also examined and demonstrated to be a new transalkylation method of amines.
- Tokitoh, Norihiro,Okazaki, Renji
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p. 3291 - 3298
(2007/10/02)
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- FLUORIDE INDUCED ALKYLATION OF α-SILOXYAMINES. A NEW METHOD FOR TRANSALKYLATION OF TERTIARY AMINES VIA THEIR N-OXIDES
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α-Siloxyamines obtained from tertiary amines via their N-oxides react with alkyl halides to give the corresponding α-siloxyammonium salts, which can be converted into new tertiary amines by fluoride induced desilylation reaction.
- Tokitoh, Norihiro,Okazaki, Renji
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p. 1937 - 1938
(2007/10/02)
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