- Regio- And Stereoselective (S N2) N -, O -, C - And S -Alkylation Using Trialkyl Phosphates
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Bimolecular nucleophilic substitution (S N 2) is one of the most well-known fundamental reactions in organic chemistry to generate new molecules from two molecules. In principle, a nucleophile attacks from the back side of an alkylating agent having a suitable leaving group, most commonly a halide. However, alkyl halides are expensive, very harmful, toxic and not so stable, which makes them problematic for laboratory use. In contrast, trialkyl phosphates are inexpensive, readily accessible and stable at room temperature, under air, and are easy to handle, but rarely used as alkylating agents in organic synthesis. Here, we describe a mild, straightforward and powerful method for nucleophilic alkylation of various N -, O -, C - and S -nucleophiles using readily available trialkyl phosphates. The reaction proceeds smoothly in excellent yield, and quantitative yield in many cases, and covers a wide range of substrates. Further, the rare stereoselective transfer of secondary alkyl groups has been achieved with inversion of configuration of chiral centers (up to 98% ee).
- Banerjee, Amit,Hattori, Tomohiro,Yamamoto, Hisashi
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- Preparation of alkylated compounds using the trialkylphosphate
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[Problem] trialkylphosphate strong base used reaction agent, a carboxylic acid, a ketone, an aldehyde, amine, amide, thiol, ester or Grignard reagent to a variety of substrates, and/or high efficiency to generate a highly stereoselective alkylation reaction, the alkylated compounds capable of producing new means. [Solution] was used as the alkylating agent in the alkylation of compound trialkylphosphate, strongly basic reaction production use. [Drawing] no
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Paragraph 0217; 0229
(2021/11/02)
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- Amide bond formation in aqueous solution: Direct coupling of metal carboxylate salts with ammonium salts at room temperature
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Herein, we report a green, expeditious, and practically simple protocol for direct coupling of carboxylate salts and ammonium salts under ACN/H2O conditions at room temperature without the addition of tertiary amine bases. The water-soluble coupling reagent EDC·HCl is a key component in the reaction. The reaction runs smoothly with unsubstituted/substituted ammonium salts and provides a clean product without column chromatography. Our reaction tolerates both carboxylate (which are unstable in other forms) and amine salts (which are unstable/volatile when present in free form). We believe that the reported method could be used as an alternative and suitable method at the laboratory and industrial scales. This journal is
- Nielsen, John,Tung, Truong Thanh
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supporting information
p. 10073 - 10080
(2021/12/10)
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- Direct amidation of acid fluorides using germanium amides
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Amide functional groups are an essential linkage that are found in peptides, proteins, and pharmaceuticals and new methods are constantly being sought for their formation. Here, a new method for their preparation is presented where germanium amides Ph3GeNR2convert acid fluorides directly to amides. These germanium amides serve to abstract the fluorine atom of the acid fluoride and transfer their amide group -NR2to the carbonyl carbon, and so function as amidation reagents.
- Hayatifar, Ardalan,Elifritz, Emily A.,Bloom, Molly B.,Pixley, Kaitlyn M.,Fennell, Christopher J.,Weinert, Charles S.
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supporting information
p. 4490 - 4493
(2021/04/12)
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- Catalytic Enantioselective α-Fluorination of 2-Acyl Imidazoles via Iridium Complexes
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The first highly enantioselective α-fluorination of 2-acyl imidazoles utilizing iridium catalysis has been accomplished. This transformation features mild conditions and a remarkably broad substrate scope, providing an efficient and highly enantioselective approach to obtain a wide range of fluorine-containing 2-acyl imidazoles which are found in a variety of bioactive compounds and prodrugs. A large scale synthesis has also been tested to demonstrate the potential utility of this fluorination method.
- Xu, Guo-Qiang,Liang, Hui,Fang, Jie,Jia, Zhi-Long,Chen, Jian-Qiang,Xu, Peng-Fei
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supporting information
p. 3355 - 3358
(2016/12/09)
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- Ru-catalyzed direct amidation of carboxylic acids with N-substituted formamides
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The direct amidation of carboxylic acids with N-substituted formamides has been accomplished via ruthenium catalysis. In the presence of ruthenium catalyst, a versatile range of carboxylic acids and N-substituted formamides undergoes amidation reaction to produce synthetically useful amides in good yields. C[dbnd]O in amide product came from benzoic acid but not N-substituted formamides, and which was confirmed by Isotope experiment.
- Bi, Xiaojing,Li, Junchen,Shi, Enxue,Wang, Hongmei,Gao, Runli,Xiao, Junhua
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p. 8210 - 8214
(2016/11/23)
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- Transfer Hydrogenation of Nitriles, Olefins, and N-Heterocycles Catalyzed by an N-Heterocyclic Carbene-Supported Half-Sandwich Complex of Ruthenium
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In the presence of KOBut, N-heterocyclic carbene-supported half-sandwich complex [Cp(IPr)Ru(pyr)2][PF6] (3) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) catalyzes transfer hydrogenation (TH) of nitriles, activated N-heterocycles, olefins, and conjugated olefins in isopropanol at the catalyst loading of 0.5%. The TH of nitriles leads to imines, produced as a result of coupling of the initially formed amines with acetone (produced from isopropanol), and showed good chemoselectivity. Reduction of N-heterocycles occurs for activated polycyclic substrates (e.g., quinoline) and takes place exclusively in the heterocycle. The TH also works well for linear and cyclic olefins but fails for trisubstituted substrates. However, the C = C bond of α,β-unsaturated esters, amides, and acids is easily reduced even for trisubstituted species, such as isovaleriates. Mechanistic studies suggest that the active species in these catalytic reactions is the trihydride Cp(IPr)RuH3 (5), which can catalyze these reactions in the absence of any base. Kinetic studies are consistent with a classical inner sphere hydride-based mechanism of TH.
- Mai, Van Hung,Nikonov, Georgii I.
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p. 943 - 949
(2016/05/09)
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- Oxidative coupling of alcohols and amines over bimetallic unsupported nanoporous gold: Tailored activity through mechanistic predictability
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An unsupported nanoporous gold catalyst is employed for the direct coupling of primary alcohols and amines to the corresponding amides in the liquid phase. Among others, the reaction of methanol and dimethylamine to the industrially relevant dimethylformamide proceeds smoothly at 40°C (turnover frequency≈40 h-1). The activation of molecular oxygen is identified as a key parameter. Doping of the unsupported catalyst by an admetal (Ru, Ag) is used to increase the activity of the catalyst considerably for this reaction (turnover frequency ≈ 100 h-1).
- Wichmann, Andre,B?umer, Marcus,Wittstock, Arne
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- Iron-catalysed, general and operationally simple formal hydrogenation using Fe(OTf)3 and NaBH4
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An operationally simple and environmentally benign formal hydrogenation protocol has been developed using highly abundant iron(iii) salts and an inexpensive, bench stable, stoichiometric reductant, NaBH4, in ethanol, under ambient conditions. This reaction has been applied to the reduction of terminal alkenes (22 examples, up to 95% yield) and nitro-groups (26 examples, up to 95% yield). Deuterium labelling studies indicate that this reaction proceeds via an ionic rather than radical mechanism.
- MacNair, Alistair J.,Tran, Ming-Ming,Nelson, Jennifer E.,Sloan, G. Usherwood,Ironmonger, Alan,Thomas, Stephen P.
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supporting information
p. 5082 - 5088
(2014/07/08)
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- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
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An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
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supporting information
p. 2955 - 2965
(2013/09/02)
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- Continuous Method For Producing Amides Of Low Aliphatic Carboxylic Acids
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The invention relates to a continuous method for producing amides, according to which at least one carboxylic acid of formula (I) R3—COON ??(I) wherein R3 is hydrogen or an optionally substituted alkyl group comprising between 1 and 4 carbon atoms, is reacted with at least one amine of formula (II) HNR1R2 ??(II) wherein R1 and R2 are independently hydrogen or a hydrocarbon group comprising between 1 and 100 C atoms, to form an ammonium salt, and said ammonium salt is then reacted to form a carboxylic acid amide, under microwave irradiation in a reaction pipe, the longitudinal axis of the pipe being oriented in the direction of propagation of the microwaves of a monomode microwave applicator.
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Page/Page column 8
(2011/06/24)
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- A novel and efficient oxidation of 1,2-amino alcohols to dialkylamides
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The oxidation of 1,2-amino alcohols and α-amino ketones can be efficiently performed using potassium hydroxide in the presence of air. This novel procedure affords carboxylic derivatives in excellent yields and high purity.
- García-Valverde, María,Pedrosa, Rafael,Vicente, Martina
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p. 2092 - 2094
(2007/10/03)
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- Orthoamides. LIV. Contributions to the chemistry of azavinylogous orthoformic acid amide derivatives
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The azavinylogous aminalester 3 reacts with primary amines to give amidines 5 and 6. In the reaction of 3 with aniline the azavinylogous amidine 7 is produced additionally to the amidine 5c. Ethylendiamine is formylated at both aminogroups, the bis-amidine 8 thus formed is transformed to the salts 9a,b. Benzoxazole and benzimidazole can be prepared from 3 and o-aminophenol and o-phenylenediamine, resp. Carboxylic acid amides, urea, thiourea, aromatic acid hydrazides 17 and the sulfonylhydrazide 19 are formylated by 3 at nitrogen to give N-acylated formamidines 14, 16, 18, 20. From 3 and aliphatic acid hydrazides 17 and alkylhydrazines, resp., can be obtained 1,2,4-triazole 21 and 1-alkyl-1,2,4-triazoles 22a,b, resp. N.N-Dimethylcyanacetamide (32) reacts with 3 and the orthoamide 4a, resp., to give a mixture of the formylated compound 34 and the amidine 33. The reaction conditions are of low influence on the ratio in which 33 and 34 are formed. The orthoamide 4b and 32 react to afford a mixture of the amidine 35 and the enamine 36. Hydrogen-sulfide acts on 3 giving N,N-dimethylthioformamide (37). From 3 and 1-alkynes 41 can be prepared the amidines 42. Hydrolysis of 42b affords phenylpropiolaldehyde (43). The alkylation of the aminalester 3 gives rise to the formation of vinylogous amidinium salts 1c and 1d, resp., additionally is formed the amide acetal 2a. The salt 1d can also be prepared from 3 and borontrifluoride-ether. Iodide reacts with N,N-dimethylformamide acetals 12a,b in an unclear, complicated manner giving orthoesters 53, N,N-dimethylformamide, alkyliodides, alcohols, ammonium iodides 46 and carbondioxide. The action of halogens on 3 affords the salts 1a,b,c,e,f depending on the chosen stoichiometric ratio. Aromatic aldehydes are suited for trapping azavinylogous carbenes formed on thermolysis of 3; 1,3-oxazoles 69 are the reaction products. From 3 and propionaldehyde the amidine 65 can be obtained with low yield. Carbondisulfide transforms 3 to the azavinylogous salt 66. The preparation of the azavinylogous orthoamide 4a is described. The thermolysis of 3 and 4a, resp., gives rise to the formation of the triaminopyrimidine 67. Treatment of 1a with lithium diisopropylamide affords the triaminopyrazine 68, which can also be obtained by thermolysis of 3 in the presence of sodium hydride. Azavinylogous carbenes are thought to be the intermediates. Wiley-VCH Verlag GmbH, 2000.
- Kantlehner, Willi,Hauber, Michael,Haug, Erwin,Schallenmueller, Claus,Regele, Claudia
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p. 682 - 699
(2007/10/03)
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- Molecular engineering. Part 5.1 Tuning the constrictive binding of container host by the atomic order of portal pillars
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Two D4h container hosts 12 and 13 with 4(CH2-O-bridge-O-CH2) portal pillars were obtained in good yields by stepwise synthetic routes and showed complementary complexation behaviors to their analogues with (O-CH2-bridge-CH2-O)4 portal pillars. 1H NMR spectral chemical shifts of host's inward-turned OCH2O protons were sensitive to guest change. The stability orders of hemicarceplexes were 12-p-(CH3CH2)2C6H4 > 12-p-(CH3O)2C6-H4 ? 12-o-(CH3O)2C6H4 > 12-m-(CH3O)2C6H4 and 13-CH3COCH2CH3 > 13-CH3COCH2CH(CH3)2 > 13-CH3-CON(CH3)2 > 13-CH3COOCH2CH3 > 13-CH3CH2CON(CH3)2 in terms of the activation energy barrier for decomplexation. Large solvent effects on the activation energy for decomplexation of hemicarceplexes were observed.
- Ihm, Chaesang,Kim, Minkyu,Ihm, Hyejae,Paek, Kyungsoo
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p. 1569 - 1575
(2007/10/03)
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- Reactivity of phosphonium diylids with esters and amides
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The phosphonium diylid (C6H5)2P(CH2)(CH2Li) reacts readily with various esters and amides to give acylated phosphonium salts and Wittig products.In the case of N,N-dimethylbenzamide the reaction can be directed mainly to the Wittig products by protonation.Depending on the nature of the carbonyl group, unexpected reactions, such as conjugate additions to α,β-unsaturated compounds or enolization of α-hydrogenated amides, can also take place.
- Cristau, Henri-Jean,Ribeill, Yves
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p. C51 - C53
(2007/10/02)
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- FORMATION OF DIALKYLAMINOACETONITRILE FROM N,N-DIALKYLAMIDES IN AN RF PLASMA
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An unprecedented transformation of N,N-dimethylamides into dimethylaminoacetonitrile (1) by passing through a 13.56 MHz gaseous discharge was found.Diethylaminoacetonitrile (2) was similarly given from N,N-dimethylformamide.
- Yajima, Tatsuhiko,Tsuchiya, Atsuhiko,Tezuka, Meguru
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p. 4177 - 4178
(2007/10/02)
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- REACTIONS OF TRIETHYLGERMYLLITHIUM WITH N,N-DIALKYLATED CARBOXAMIDES
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The reactions of triethylgermyllithium with N,N-dialkylated carboxamides have been investigated.N,N-Dimethylacetamide, N,N-dimethylpivalamide, N,N-diethyltrifluoroacetamide and N,N-diethylbenzamide act on triethylgermyllithium, which is made from bis(triethylgermyl)mercury and lithium in hexane, to release the corresponding acyltriethylgermanes as the principal product.The regioselectivity of the present reactions was found to depend markedly on the reaction conditions and the nature of the acyl fragment of amides.Thus, triethylgermyllithium reacts with N,N-dimethylacetamide as metallating agent to give lithium N,N-dimethylacetamide, if the reaction is carried out in tetrahydrofuran solution.Mechanistic interpretations of these results are discussed.
- Bravo-Zhivotovskii, D. A.,Pigarev, S. D.,Kalikhman, I. D.,Vyazankina, O. A.,Vyazankin, N. S.
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- SYNTHESIS OF γ-KETOPIMELIC ACID DERIVATIVES BY RHODIUM CARBONYL-CATALYZED HYDROCARBONYLATION OF ACRYLIC ACID DERIVATIVES
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The rhodium carbonyl-catalyzed reactions of acrylic acid derivatives (1) with CO in iso-propanol gave selectively γ-ketopimelic acid derivatives (2) in good yields.In the reaction of ethyl acrylate (1b) in iso-propanol-d8, deuterium scrambling in the methylene groups of the products (2b) was observed.
- Hong, Pangbu,Mise, Takaya,Yamazaki, Hiroshi
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p. 361 - 364
(2007/10/02)
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- UNSATURATED THIOLATES IN CYCLOADDITION REACTIONS. III. REACTION OF 1-N,O,S-SUBSTITUTED 2-ALKYL- AND 2-PHENYL-1-ETHENETHIOLATES WITH CARBON BISULFIDE
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The reaction of 1-N,O,S-substituted 1-ethenethiolates with carbon bisulfide leads to the formation of cyclic adducts.The reaction rate decreases in the order N > O > S.In the case of the 1-N- and 1-S-substituted 1-ethenethiolates the reaction products are 5-N- and 5-S-substituted 1,2-dithiole-3-thiones.In the case of the 1-O-substituted 1-ethenethiolates the reaction goes further with the formation of 3,3'-spirobi(1,2-dithiole).The relation reaction rate constants for 1-N,N-dimethylamino-2H-, 1-N,N-dimethylamino-2-methyl-, and 1-N,N-dimethylamino-2-phenyl-1-ethenethiolates are 1, 4.2 and 10 respectively.
- Bunina, N. A.,Petrov, M. L.,Petrov, A. A.
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