Reactions Of Carboxylic Acid Derivatives Research Articles

Emerging Nickel Catalysis in Ketones Synthesis Using Carboxylic Acid Derivatives

AbstractNickel catalysis in cross‐coupling reaction of carboxylic acid derivatives (CADs) with various coupling partners to access ketones has grown steadily in last five decades and substantially contributed to this area. These synthetic protocols have afforded various unique privileges: 1) robust approach to access ketones in a stereo defined manner; 2) reduced byproduct formation; 3) broad substrate scope with high functional group tolerance and 4) avoids direct use of fatal carbon monoxide. Herein, an overview of acyl‐nickel complexes reactivity, major mechanistic pathways in ketones synthesis, rational aspects of nickel catalysis with CADs and highlights of synthetic applications will be described in detail. The main objective of this review is demonstration of historical development of nickel catalysis with CADs to access ketones from year 1970 to 2020 and introductory remarks of current state of work progress in this area.

Nickel-Catalyzed Decarbonylative Amination of Carboxylic Acid Esters.

The reaction of carboxylic acid derivatives with amines to form amide bonds has been the most widely used transformation in organic synthesis over the past century. Its utility is driven by the broad availability of the starting materials as well as the kinetic and thermodynamic driving force for amide bond formation. As such, the invention of new reactions between carboxylic acid derivatives and amines that strategically deviate from amide bond formation remains both a challenge and an opportunity for synthetic chemists. This report describes the development of a nickel-catalyzed decarbonylative reaction that couples (hetero)aromatic esters with a broad scope of amines to form (hetero)aryl amine products. The successful realization of this transformation was predicated on strategic design of the cross-coupling partners (phenol esters and silyl amines) to preclude conventional reactivity that forms inert amide byproducts.

A simple and versatile method to synthesize N-acyl-benzotriazoles

An efficient method for the synthesis of N-acyl-benzotriazoles from a wide variety of protected amino acids, as well as from compounds frequently used in drug discovery such as biotin and N-Fmoc polyethylene glycol, has been developed. The reaction of carboxylic acid derivatives with benzotriazole in the presence of T3P® yielded the corresponding N-acyl-benzotriazoles, which were obtained in high purity following a simple work-up procedure, in most cases via precipitation of the desired product in water.

Lewis Acid Catalysis of Nb2O5 for Reactions of Carboxylic Acid Derivatives in the Presence of Basic Inhibitors

AbstractThis review focuses on catalytic applications of niobium pentoxide (Nb2O5) and niobic acid (Nb2O5 ⋅ nH2O). These materials serve as heterogeneous acid catalysts that show excellent activity and selectivity for various types of reactions including hydrations, dehydrations, and oxidations. Most recently, they have been used for dehydration reactions of polyols and nucleophilic substitution reactions of carboxylic acid derivatives. A special focus is placed on the latter reactions, where superficial Nb5+ cations act as Lewis‐acidic sites that activate oxygen‐containing functional groups of substrates even in the presence of basic inhibitors such as water or amines. This unique behavior of Nb‐oxide‐based catalysts is a consequence of their Lewis acidity, which is characterized by their ability to simultaneously activate C=O bonds but not to engage in strong competitive adsorption of base molecules. Both experimental and theoretical investigations are presented in order to assess the characteristic features of the Nb‐oxide‐based catalysts together with their structural features.

Amidation Reaction of Carboxylic Acid with Formamide Derivative Using SO3·pyridine

The amidation reaction of carboxylic acid derivatives was developed using sulfur trioxide pyridine complex (SO3·py) as a commercially available and easily handled oxidant. This method could be applied to the reaction of various aromatic and aliphatic carboxylic acids, including optically active ones, with formamide derivatives to afford the corresponding amides in good to high yields.

ChemInform Abstract: Convergent Three‐Component Tetrazole Synthesis.

AbstractMicrowave assisted reaction of carboxylic acid derivatives, amines, and TmsN3 provides 1,5‐disubstituted and various 1,5‐fused tetrazoles.

ChemInform Abstract: Efficient Transition Metal‐Catalyzed Reactions of Carboxylic Acid Derivatives with Hydrosilanes and Hydrosiloxanes, Afforded by Catalyst Design and the Proximity Effect of Two Si—H Groups

AbstractReview: [89 refs.

Efficient Transition Metal-Catalyzed Reactions of Carboxylic Acid Derivatives with Hydrosilanes and Hydrosiloxanes, Afforded by Catalyst Design and the Proximity Effect of Two Si–H Groups

The discovery of the ruthenium cluster μ3,-(η2:η3:η5-acenaphythylene)Ru3(CO)7 (1), which is active in catalytic reactions involving Si–H bond activation, and the rate enhancement by the proximity effect of two Si–H groups enabled the reduction of carboxylic acid derivatives with hydrosilanes under mild reaction conditions. A judicious choice of the hydrosilane and of the additives led to a remarkably selective reduction. Besides simple reduction, the treatment of carboxylic acid derivatives with hydrosilanes in the presence of 1 led to new reactions involving several C–O and C–C bond-forming as well as C–O bond-cleavage steps. These reactions included polymerization, rearrangement, and aromatic substitution. The use of inexpensive 1,1,3,3-tetramethyldisiloxane (TMDS) facilitated the efficient reduction of amides to amines using either 1, commercially available platinum compounds, or environmentally friendly iron complexes. The conversion of tertiary amides into aldenamines was achieved by iridium catalysis. In the ruthenium-, iridium-, platinum-, and iron-catalyzed reduction of amides, the use of the reducing reagent polymethylhydrosiloxane (PMHS) resulted in self-encapsulation of the residual metal species into the formed silicone gel to give the ‘metal-free’ product in a straightforward way. 1 Introduction 2 Two Key Preliminary Investigations 2.1 A Ruthenium Cluster for Si–H Bond Activation 2.2 Proximity Effect of Two Si–H Groups for Rate Enhancement 3 Ruthenium-Catalyzed Reduction of Carboxylic Acid Derivatives 3.1 From Ketones to Less Reactive Carboxylic Acid Derivatives 3.2 Self-Encapsulation of the Residual Metals into Silicone Gel 4 Extension to C–O and C–C Bond-Forming Reactions 4.1 Reduction versus Ring-Opening Polymerization of Cyclic Ethers 4.2 Polymerization versus Rearrangement of Vinyl Ethers 4.3 Is ‘R3Si+’ Involved in the Reactions? 4.4 Applications of ‘R3Si+’-Mediated Reactions 5 Reductions with Unique Selectivity 6 Surfing the Periodic Table 7 Concluding Remarks

Effects of substituents on activation parameters in the reactions of carboxylic acid derivatives with anionic and neutral nucleophiles

Changes of activation parameters, ΔH‡ and ΔS‡, with σ constants of substituents in the reactions of carboxylic acid derivatives with anionic and neutral nucleophiles in various solvents give the δΔH‡ and δΔS‡ reaction constants which are linearly related for variations of substituents in substrate and nucleophile. The dependences obtained, δΔH‡vs.δΔS‡, allow estimation of the contribution of changes of the internal enthalpy, δΔH‡int, to the enthalpy reaction constant, δΔH‡, which give a single linear dependence on the Hammett ρ reaction constants. The results obtained show that the substituent effects on the charge development in the transition state are governed by the magnitude of δΔH‡int.

Ring-Opening Polymerization of Lactide To Form a Biodegradable Polymer

In this laboratory activity for introductory organic chemistry, students carry out the tin(II) bis(2-ethylhexanoate)/benzyl alcohol mediated ring-opening polymerization of lactide to form the biodegradable polymer polylactide (PLA). As the mechanism of the polymerization is analogous to that of a transesterification reaction, the experiment can be used to demonstrate reactions of carboxylic acid derivatives. The polymerization can be successfully carried out using standard teaching laboratory (non-Schlenk) conditions. Analysis of polymer stereochemistry by 1H NMR and a discussion of the effect of monomer stereochemistry on the stereochemistry of the polymer are included in the experiment. The effect of adventitious water on the rate of the polymerization and the number-average molecular weight, Mn of the resulting polymer are discussed in the Supplemental Material.

A Guided-Inquiry Approach to the Sodium Borohydride Reduction and Grignard Reaction of Carbonyl Compounds

The guided-inquiry approach is applied to the reactions of sodium borohydride and phenyl magnesium bromide with benzaldehyde, benzophenone, benzoic anhydride, and ethyl benzoate. Each team of four students receives four unknowns. Students identify the unknowns and their reaction products by using the physical state of the unknown, an instructor-provided list of potential products, IR spectra of liquid unknown products, and melting points of solid unknown products. Students use their data to deduce that esters are less electrophilic than the other carbonyl compounds in this set, that Grignard reagents are more nucleophilic than sodium borohydride, and that carboxylic acid derivatives do not undergo the nucleophilic addition reactions that are characteristic of aldehydes and ketones. Using their experimental data, students are able to propose a plausible mechanism for the reaction of carboxylic acid derivatives with strong nucleophiles.

A Novel Synthesis of N-Methoxy-N-methylamides from 4,6-Pyrimidyl Urethane and Grignard Reagents

The N-methoxy-N-methylamides (Weinreb amides) have enjoyed tremendous popularity because they react with organometallics (RM, M=Li, MgX) to provide various ketones through stable metal-chelated intermediates without side products. Among the various methods for the preparation of N-methoxy-N-methylamides, the condensation of carboxylic acids and N,O-dimethylhydroxylamine hydrochloride (MeONH2MeCl) using peptide coupling reagents has been frequently employed. The treatment of carboxylic acids with Ph3P/CBr4, Bu3P/(2-pyridine-N-oxide)disulfide, 1,1'-carbonyldiimidazole (CDI), S,S-di(2-pyridyl)dithiocarbonate, DCC/HOBT, 2-halo-1-methylpyridinium iodide, BOP, HBTU, and 2-chloro-4,6-dimethoxy[1.3.5]triazine (CDMT) in the presence of base gives the activated ester intermediates, which are converted to the corresponding Nmethoxy-N-methylamides by nucleophilic acyl substitution with MeONHMe. Although most of these methods are especially useful for the preparation of N-methoxy-Nmethylamides of N-protected α-amino acids without any racemization, some of them require the use of an excess of base and coupling reagents such as BOP and HBTU are expensive. The conversion of carboxylic acids to the corresponding N-methoxy-N-methylamides can also be carried out via anhydride intermediates. The treatment of carboxylic acids with trimethylacetyl chloride, alkyl chloroformates, and phosphonate reagents (DEPC and PPA) affords in situ anhydrides, mixed anhydrides, and phosphonic anhydrides, respectively, in the presence of base, which are converted to the corresponding N-methoxy-N-methylamides by nucleophilic displacement with MeONHMe. However, the removal of isobutyl alcohol is often tedious in case of using isobutyl chloroformate and phosphonate reagents are expensive. The recent method via acyl mesylates, generated from carboxylic acids and methanesulfonyl chloride, is especially useful for the preparation of sterically hindered N-methoxy-N-methylamides, but it can be complicated by the formation of Nmethoxy-N-methylmethanesulfonamides as by-products. Alternatively the preparation of N-methoxy-N-methylamides has been accomplished by the reaction of carboxylic acid derivatives and MeONH2MeCl. The treatment of acid chlorides, carboxylic esters, and oxazolidinones/thiazolidinones with MeONH2MeCl/pyridine, MeONMeM (M = Li, MgCl), AlMe3/MeONH2MeCl, respectively, affords the corresponding N-methoxy-N-methylamides, but these methods proceed in two steps from carboxylic acids. Although various methods for the preparation of N-methoxy-N-methylamides have been reported, they only afford 1 equiv of N-methoxyN-methylamides from carboxylic acids or their derivatives. As part of our continuing study on the preparation of Nmethoxy-N-methylamides we report that N-methoxy-Nmethylamides can be novely prepared from 4,6-pyrimidyl urethane and Grignard reagents in high yields. 4,6-Pyrimidyl urethane 1 was prepared by the addition of 2 equiv of N-methoxy-N-methylcarbamoyl chloride 3, prepared from one third equiv of bis(trichloromethyl)carbonate and MeONH2MeCl, to a mixture solution of 1 equiv of 4,6-dihydroxypyrimidine 2 and 2 equiv of triethyl-

Tetrahedral Intermediates in Reactions of Carboxylic Acid Derivatives with Nucleophiles

AbstractFor Abstract see ChemInform Abstract in Full Text.

Tetrahedral intermediates in reactions of carboxylic acid derivatives with nucleophiles

AbstractTransacylation reactions of carboxylic acids, carboxylic acid esters, carboxylic acid amides and other carboxylic acid derivatives are among the most widespread and most important reactions in chemistry and biochemistry. Already in 1887, Claisen suggested a tetrahedral intermediate in transformations of carboxylic acid derivatives with nucleophiles. A historical overview gives insight into the studies to detect possible tetrahedral intermediates in such reactions. However, only in recent years has detailed information concerning the structures of such species become available. In this review, neutral, cationic and anionic tetrahedral intermediates are described which serve as models for transacylations under neutral, acid‐catalysed or basic conditions. The characteristically different structures correspond nicely with experimental experience with reactions of carboxylic acid derivatives and with quantum chemical model calculations on tetrahedral intermediates. Finally, by means of model calculations, an explanation is given for the fast reactions of Weinreb amides, RC(O)N(CH3)OCH3, with organolithium and even with Grignard reagents: the reactions are determined by comparatively stable chelate transition states. Copyright © 2004 John Wiley & Sons, Ltd.

Evaluation of the steric substituent effect by ΩS: reinvestigation of the reaction dependency of the steric substituent constant

Using the OMEGAS program, two sets [ΩS(0.5,0.5) and ΩS(0.9,0.5)] of steric substituents were calculated by assuming different sizes of effective radii for the reaction center atom. The former set reproduces the steric substituent effect on the nucleophilic reactions of carboxylic acid derivatives better; the latter set is far better for the reactions of amines and alcohol derivatives. Our results clearly show that the effective size of the reaction center atom is another important factor in characterizing the steric effect in addition to the bulkiness of the substituent. This can be rationalized by the fact that such a general steric constant cannot be used to evaluate all sorts of steric effects using a single set of substituent constants. Copyright © 2001 John Wiley & Sons, Ltd.

Evaluation of the steric substituent effect by ΩS: reinvestigation of the reaction dependency of the steric substituent constant

AbstractUsing the OMEGAS program, two sets [ΩS(0.5,0.5) and ΩS(0.9,0.5)] of steric substituents were calculated by assuming different sizes of effective radii for the reaction center atom. The former set reproduces the steric substituent effect on the nucleophilic reactions of carboxylic acid derivatives better; the latter set is far better for the reactions of amines and alcohol derivatives. Our results clearly show that the effective size of the reaction center atom is another important factor in characterizing the steric effect in addition to the bulkiness of the substituent. This can be rationalized by the fact that such a general steric constant cannot be used to evaluate all sorts of steric effects using a single set of substituent constants. Copyright © 2001 John Wiley & Sons, Ltd.

Chemical modification of hyperbranched ultrathin films on gold and polyethylene

Synthetic methods for modifying the carboxylic acid groups of hyperbranched thin film grafts were studied. Amidation, esterification, reduction, and alkylation reactions of carboxylic acid derivatives that proceed in high conversion (>90%) are described. The stability of ultrathin, hyperbranched film grafts attached to self-assembled monolayers on gold to conditions of strong base, strong acid, heat, and organic solvents is detailed. Practical procedures that can be used to prepare and modify poly(acrylic acid) hyperbranched grafts on gold, polyethylene film, and powder for use in the synthesis of cationic polyelectrolyte grafts, for use in the synthesis of poly(allyl alcohol) grafts, for use in the synthesis of poly(allyl ester) grafts, and for use as substrates for organometallic chemistry and further graft chemistry are discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3944–3953, 2000

ChemInform Abstract: Asymmetric Diels‐Alder Reaction Catalyzed by a Chiral Titanium Reagent.

AbstractThe absolute stereochemistry of Diels‐Alder reactions of carboxylic acid derivatives (I) and (IV) with (II), isoprene or (V) can be controlled by employing Ti complexes with chiral diols derived from tartaric acid.

ChemInform Abstract: Reactions of Carboxylic Acid Derivatives with Superoxide.

AbstractThe mechanisms of the reactions of superoxide (O·‐ 2) and in some cases ozonate (O·‐ 3) with the carboxylic acid derivatives (Ia)‐(Ic), (II)‐(IV) are investigated.

Reactions of carboxylic acid derivatives with superoxide

The mechanisms of the reactions of superoxide with carboxylic esters, acyl peroxides, and the acyl chlorides of α- and β-bromocarboxylic acids have been investigated. Experimental evidence is presented supporting the view that (a) conversion of an ester into its carboxylic acid does not proceed via the corresponding acyl peroxide; (b) conversion of acyl peroxide into carboxylic acid by superoxide involves either electron transfer to or an SN2 reaction on the peroxidic group; (c)α-bromoacyl chlorides with superoxide give the corresponding aldehyde via a cyclic peroxidic intermediate.