Conversion Of Carboxylic Acids Research Articles

3d-Metal-Catalyzed Single-Electron-Transfer-Induced Conversion of Carboxylic Acids and Their Equivalents

AbstractThis account describes the latest developments on 3d-metal-catalyzed single-electron-transfer (SET)-induced strategies that use carboxylic acids and their synthetic equivalents as substrates. In general, 3d-metal-promoted SET-mediated transformations of free carboxylic acids proceed readily via the formation of carboxylate radicals, whilst those of carboxylic acid equivalents, bearing an N-donor substituent, proceed via the formation of α-carbo radicals. The advantages of these strategies combine the low-cost of carboxylic acid starting materials and 3d metal catalysts with the possibility of realizing structurally diverse ranges of compounds in an atom- and step-economic manner. Developments primarily achieved by our group and a few by other researchers on this topic are discussed in this account.1 Introduction2 Mechanistic Considerations of 3d-Metal-Catalyzed SET-Mediated Transformations3 Developments Based on SET-Mediated Transformations of Carboxylic Acids4 Developments Based on SET-Mediated Transformations of Carboxylic Acid Equivalents5 Conclusion and Outlook

Formal Transformation of Benzylic Carboxylic Acids to Phenols.

Phenols play a crucial role as core structural motifs in natural products and also serve as fundamental building blocks in synthetic chemistry. Apart from the known protocols for the conversion of aryl precursors to phenols (i.e., decarboxylative oxygenation), we report here the efficient synthesis of phenols from the stable and readily available benzylic carboxylic acids under mild reaction conditions. The photocatalytic conversion of carboxylic acids to peroxides is a crucial step in this strategy, allowing the subsequent C-O bond formation via Hock rearrangement.

Conversion of Carboxylic Acids to Sulfonamide Bioisosteres via Energy Transfer Photocatalysis.

More than 450 drugs containing a carboxylic acid functional group have been marketed worldwide. Herein, we report a concise and environmentally friendly organic photoinduced protocol for the interconversion of carboxylic acids into their bioisosteres. With this strategy, a variety of substrates, including alkyl, (hetero)aryl, and alkenyl acids, as well as various biologically relevant acids are successfully converted into primary sulfonamides.

Modular alkene synthesis from carboxylic acids, alcohols and alkanes via integrated photocatalysis.

Alkenes serve as versatile building blocks in diverse organic transformations. Despite notable advancements in olefination methods, a general strategy for the direct conversion of carboxylic acids, alcohols and alkanes into alkenes remains a formidable challenge owing to their inherent reactivity disparities. Here we demonstrate an integrated photochemical strategy that facilitates a one-pot conversion of these fundamental building blocks into alkenes through a sequential C(sp3)-C(sp3) bond formation-fragmentation process, utilizing an easily accessible and recyclable phenyl vinyl ketone as the 'olefination reagent'. This practical method not only offers an unparalleled paradigm for accessing value-added alkenes from abundant and inexpensive starting materials but also showcases its versatility through various complex scenarios, including late-stage on-demand olefination of multifunctional molecules, chain homologation of acids and concise syntheses of bioactive molecules. Moreover, initiating from carboxylic acids, alcohols and alkanes, this protocol presents a complementary approach to traditional olefination methods, making it a highly valuable addition to the research toolkit for alkene synthesis.

Significant production of alkyl halides from (aliphatic) carboxylic acids in the UV/chlorine process

Ultraviolet radiation combined with free chlorine (UV/chlorine) is an attractive alternative to UV or chlorination alone for disinfection. However, •OH and Cl• radicals from UV/chlorine have recently raised increasing concerns about the possible formation of chlorinated products. A significant quantity of alkyl halides was generated from aliphatic carboxylic acids in the UV/chlorine process, in contrast to the absence of any detectable alkyl halides during chlorination alone. During the UV/chlorine process, the formation of CH3Cl, CH3CH2Cl and CH3CH2CH2Cl were was observed from acetic acid, propionic acid and n-butyric acid, respectively. The maximum yield of CH3Cl was up to 54.6 % when acetic acid was treated at a chlorine to precursors (Cl/P) ratio of 4.0. In addition to CH3Cl, CH2Cl2 and CHCl3 were also detected as the products of acetic acid. The presence of bromide ions resulted in a reduction in the yields of chloroalkanes, the formation of bromine byproducts, and an increase in the total amount of halocarbons. Hydroxyl radicals and chlorine radicals were identified as key reactants in the radical quenching experiments. The reactions described in this paper contribute to the understanding of the mechanism of halogenated byproduct formation during the UV/chlorine process. SynopsisThe radicals resulting from UV/chlorine lead to the conversion of carboxylic acids into a significant amount of alkyl halides that would not be generated by chlorination alone.

Low-Temperature Wastewater Electrolysis for H2 and Clean Water Generation

Water electrolysis represents a sustainable approach to produce green hydrogen (H2); however, the high energy cost (H2O → 2H+ + 2e- + ½O2, ∆H° = 275 kJ/mol H2, E° = −1.18 V) associated with water electrolysis and electricity cost (>$50/MWh) results in a minimum H2 selling price ≈$4/kg H2. Hence, we need to find alternative process to generate H2 to meet the current U.S. Department of Energy's (DOE's) Energy Earthshots of $1/kg H2 in one decade.Wastewater electrolysis represents an alternative approach to generate H2 with renewable sources by electrochemically oxidizing organic molecules to generate H2 (e.g., CH3COOH + 2H2O → 2CO2 + 8e- + 8H+, ∆H° = 53 kJ/mol, E° = −0.02 V,) which has up to 5 times lower energy requirement than water electrolysis. As opposed to water electrolysis that requires clean water streams, wastewater electrolysis uses readily available waste streams that need cleanup anyway to generate H2; hence, integrating a second application in addition to H2 generation.1-3 In this work, we compare the performance of heterogeneous electrocatalysts for the electrocatalytic oxidation (ECO) of organic molecules present in wastewater as well as electrocatalysts for the H2 evolution reaction (HER) at room temperature. ECO electrocatalysts were developed and tested using real wastewaters derived from several sources including the hydrothermal liquefaction (HTL) of food waste. We synthesized the ECO electrocatalysts using both platinum-group metals (PGM) as well as base-group metals (BGM) with equimolar loadings and tested them as a function of half-cell potential. Our results show that both PGM- and BGM-based bimetallics improve the activity and stability compared to the baseline RuO2-based catalysts4-6. We performed a preliminary techno-economic analysis and showed that the levelized costs of using this technology to process the wastewater alone is equivalent to that of traditional wastewater processing. The sale of the produced H2 co-product will decrease the levelized processing cost below that of current wastewater processing. References Andrews, E.; Lopez-Ruiz, J. A.; Egbert, J. D.; Koh, K.; Sanyal, U.; Song, M.; Li, D.; Karkamkar, A. J.; Derewinski, M. A.; Holladay, J.; Gutiérrez, O. Y.; Holladay, J. D., Performance of Base and Noble Metals for Electrocatalytic Hydrogenation of Bio-Oil-Derived Oxygenated Compounds. ACS Sustainable Chemistry & Engineering 2020, 8 (11), 4407-4418.Lopez-Ruiz, J. A.; Qiu, Y.; Andrews, E.; Gutiérrez, O. Y.; Holladay, J. D., Electrocatalytic valorization into H2 and hydrocarbons of an aqueous stream derived from hydrothermal liquefaction. Journal of Applied Electrochemistry 2021, 51 (1), 107-118.Lopez-Ruiz, J. A.; Andrews, E.; Akhade, S. A.; Lee, M.-S.; Koh, K.; Sanyal, U.; Yuk, S. F.; Karkamkar, A. J.; Derewinski, M. A.; Holladay, J.; Glezakou, V.-A.; Rousseau, R.; Gutiérrez, O. Y.; Holladay, J. D., Understanding the Role of Metal and Molecular Structure on the Electrocatalytic Hydrogenation of Oxygenated Organic Compounds. ACS Catalysis 2019, 9 (11), 9964-9972.Qiu, Y.; Lopez-Ruiz, J. A.; Zhu, G.; Engelhard, M. H.; Gutiérrez, O. Y.; Holladay, J. D., Electrocatalytic decarboxylation of carboxylic acids over RuO2 and Pt nanoparticles. Appl. Catal. B-Environ. 2022, 305, 121060.Lopez-Ruiz, J. A.; Qiu, Y.; Andrews, E.; Gutiérrez, O. Y.; Holladay, J. D., Electrocatalytic valorization into H2 and hydrocarbons of an aqueous stream derived from hydrothermal liquefaction. J. Appl. Electrochem. 2021, 51 (1), 107-118.Qiu, Y.; Lopez-Ruiz, J. A.; Sanyal, U.; Andrews, E.; Gutiérrez, O. Y.; Holladay, J. D., Anodic electrocatalytic conversion of carboxylic acids on thin films of RuO2, IrO2, and Pt. Appl. Catal. B-Environ. 2020, 277, 119277. Figure 1

Performance of catalytic wet oxidation on thermochemical aqueous effluents assessed by FT-ICR MS

Aqueous phase (AP) is frequently observed in bio-oil from biomass thermochemical conversion or as an upgrading coproduct. However, AP contains high organic content that can be toxic and that must be reduced or removed to be then treated in existing wastewater plants. A promising method to upgrade these APs is the catalytic wet peroxide oxidation (CWPO) that was applied here on APs of both hydrothermal liquefaction and pyrolysis bio-oils from softwood and hardwood. Efficiency of the CWPO was assessed by investigating the molecular composition of raw and treated APs by ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with electrospray ionization (ESI) in negative- and positive-ion modes. Combination of FT-ICR MS and multivariate statistical analyses evidenced efficiency of the process with new compounds resulting from the oxidative depolymerization, characterized by lower unsaturation degree and molecular weight, and higher oxygen atom count. Refractory compounds were also observed, which are notably characterized by high unsaturation degrees. Interestingly, both detection modes were shown to be complementary for the understanding of the CWPO process. ESI (-) allowed to assess the completion of the oxidation process in detecting carboxylic acid conversion products and to specifically evidence refractory products. ESI (+) was informative on the CWPO process, especially on the conversion of the basic compounds, with the decrease of the detected species. Eventually, softwood AP was shown to be more reluctant to CWPO than the hardwood one.

Cell-free reduction of carboxylic acids with secreted carboxylic acid reductase

Mycobacterium marinum CAR (MmCAR) is one of the most widely used CARs as the key enzyme for the synthesis of aldehydes, alcohols and further products from the respective carboxylic acids. Herein, we describe the first functionally secreted 131 kDa CAR and its isolated A-domain using Komagataella phaffii and a methanol-free constitutive expression strategy. Precipitated and lyophilized MmCAR (500 µg) was isolated from the culture supernatant and showed no decrease in activity for piperonylic acid (80% conversion), even when stored for up to 3 weeks at 4°C. Lyophilized MmCAR precipitate gave 48% yield of E/Z-nonanal-4-nitrobenzoyloxime from the reduction of nonanoic acid and in-situ derivatization with O-4-nitrobenzoyl-hydroxylamine. Furthermore, K. phaffii could successfully secrete the MmCAR adenylation domain. Its activity was confirmed by the amidation of benzoic acid with n-hexylamine. Neither enzyme variant was glycosylated by the yeast. In summary, functional CAR can be secreted by K. phaffii and used for cell free conversion of carboxylic acids to various products.

Direct conversion of carboxylic acids to free thiols via radical relay acridine photocatalysis enabled by N-O bond cleavage.

Carboxylic acids and thiols are basic chemical compounds with diverse utility and widespread reactivity. However, the direct conversion of unprotected acids to thiols is hampered due to a fundamental problem - free thiols are incompatible with the alkyl radicals formed on decarboxylation of carboxylic acids. Herein, we describe a concept for the direct photocatalytic thiolation of unprotected acids allowing unprotected thiols and their derivatives to be obtained. The method is based on the application of a thionocarbonate reagent featuring the N-O bond. The reagent serves both for the rapid trapping of alkyl radicals and for the facile regeneration of the acridine-type photocatalyst.

Pyridine-borane complex-catalysed thioesterification: the direct conversion of carboxylic acids to thioesters.

Thioesters are a common class of biologically active fragments and synthetically useful building blocks. An attractive synthetic approach would be to use simple and bench-stable carboxylic acids as a coupling partner. Herein, we present a 4-bromo pyridine-borane complex as a catalyst for the direct coupling of carboxylic acids with thiols. A wide range of thioesters with good functional group compatibility could be prepared via this metal-free approach. The merit of this strategy is exemplified by the modification of carboxylic acid-containing drugs.

New Route to Direct Synthesis of Symmetrical Ureas from Carboxylic Acids

AbstractThe first method for the direct conversion of carboxylic acids into ureas has been developed. The classical procedures described for the formation of ureas from carboxylic acids require two steps, preparation of the isocyanate followed by its aminolysis. In this work, aryl carboxylic and arylalkyl carboxylic acids have been transformed into symmetric ureas in a single step using DPPA or sodium azide as nitrogen source. The addition of water (method A) or the presence of solvent water (method B) was essential for the formation of symmetrical ureas from the corresponding carboxylic acids. The corresponding ureas have been obtained in good to excellent yields of 46 to 100%. This procedure is compatible with different substituents present in the starting carboxylic acid.

Low-Temperature Wastewater Electrolysis for H2 and Clean Water Generation

Water electrolysis represents a sustainable approach to produce green hydrogen (H2); however, the high energy cost (H2O → 2H+ + 2e- + ½O2, ∆H° = 275 kJ/mol H2, E° = −1.18 V) associated with water electrolysis and electricity cost (>$50/MWh) results in a minimum H2 selling price ≈$5/kWh. Hence, we need to find alternative process to generate H2 to meet the current U.S. Department of Energy's (DOE's) Energy Earthshots of $1/kg H2 in one decade.Wastewater electrolysis represents an alternative approach to generate H2 with renewable sources by electrochemically oxidizing organic molecules to generate H2 (e.g., CH3COOH + 2H2O → 2CO2 + 8e- + 8H+, ∆H° = 53 kJ/mol, E° = −0.02 V,) which has up to 5 times lower energy requirement than water electrolysis. As opposed to water electrolysis that requires clean water streams, wastewater electrolysis uses readily available waste streams that need cleanup anyway to generate H2; hence, integrating a second application in addition to H2 generation.1-3 In this work, we compare the performance of heterogeneous electrocatalysts for the electrocatalytic oxidation (ECO) of organic molecules present in wastewater as well as electrocatalysts for the H2 evolution reaction (HER) at room temperature. ECO and HER electrocatalysts were developed and tested using real wastewaters derived from the hydrothermal liquefaction (HTL) of food waste. We synthesized the electrocatalysts using both platinum-group metals (PGM) as well as base-group metals (BGM) with equimolar loadings and tested them as a function of potential. Our results show that while PGM-based electrocatalysts were required to perform ECO of HTL-derived wastewater4-6, BGM-based electrocatalysts were able to perform HER similarly to PGM electrocatalysts in HTL-derived wastewater. We performed a preliminary techno-economic analysis to outline a path towards $1/kg H2 via wastewater electrolysis and identified the next research and development areas. References Andrews, E.; Lopez-Ruiz, J. A.; Egbert, J. D.; Koh, K.; Sanyal, U.; Song, M.; Li, D.; Karkamkar, A. J.; Derewinski, M. A.; Holladay, J.; Gutiérrez, O. Y.; Holladay, J. D., Performance of Base and Noble Metals for Electrocatalytic Hydrogenation of Bio-Oil-Derived Oxygenated Compounds. ACS Sustainable Chem. Eng. 2020, 8 (11), 4407-4418.Lopez-Ruiz, J. A.; Qiu, Y.; Andrews, E.; Gutiérrez, O. Y.; Holladay, J. D., Electrocatalytic valorization into H2 and hydrocarbons of an aqueous stream derived from hydrothermal liquefaction. J. Appl. Electrochem. 2021, 51 (1), 107-118.Lopez-Ruiz, J. A.; Andrews, E.; Akhade, S. A.; Lee, M.-S.; Koh, K.; Sanyal, U.; Yuk, S. F.; Karkamkar, A. J.; Derewinski, M. A.; Holladay, J.; Glezakou, V.-A.; Rousseau, R.; Gutiérrez, O. Y.; Holladay, J. D., Understanding the Role of Metal and Molecular Structure on the Electrocatalytic Hydrogenation of Oxygenated Organic Compounds. ACS Catalysis 2019, 9 (11), 9964-9972.Qiu, Y.; Lopez-Ruiz, J. A.; Zhu, G.; Engelhard, M. H.; Gutiérrez, O. Y.; Holladay, J. D., Electrocatalytic decarboxylation of carboxylic acids over RuO2 and Pt nanoparticles. Appl. Catal. B-Environ. 2022, 305, 121060.Lopez-Ruiz, J. A.; Qiu, Y.; Andrews, E.; Gutiérrez, O. Y.; Holladay, J. D., Electrocatalytic valorization into H2 and hydrocarbons of an aqueous stream derived from hydrothermal liquefaction. J. Appl. Electrochem. 2021, 51 (1), 107-118.Qiu, Y.; Lopez-Ruiz, J. A.; Sanyal, U.; Andrews, E.; Gutiérrez, O. Y.; Holladay, J. D., Anodic electrocatalytic conversion of carboxylic acids on thin films of RuO2, IrO2, and Pt. Appl. Catal. B-Environ. 2020, 277, 119277. Figure 1

Catalytic enantioselective Gilman-Speeter synthesis of β-lactams by nucleophilic activation of carboxylic acids

A novel Gilman-Speeter synthesis of β-lactams has been developed that was rendered highly enantioselective by virtue of isothiourea catalyst’s nucleophilicity. This process depends upon the HATU conversion of carboxylic acids to activated esters which then undergo attack by the homochiral catalyst and subsequently deprotonated by inorganic base to furnish catalytic quantities of the corresponding enolate ions that react with imines to provide the requisite β-lactams in good yields and enantiomeric excesses.

Palladium hydride promotion by KHCO3 enhances the decarboxylation rate

Direct conversion of carboxylic acids to alkanes by decarboxylation on PdHx is an effective way to defunctionalize biomass-derived feedstocks. This catalytic decarboxylation generally suffers from low activity and selectivity loss by competing hydrogenation routes. Anchoring the carboxylate group with K+ on PdHx/C increases the rate of decarboxylation by more than one order of magnitude. Temperature-programmed desorption of CO2 shows that the modification increases the surface basicity. In turn, this induces dissociative adsorption of the acid carboxylic group. The resulting adsorption as carboxylate facilitates the C–C bond cleavage by weakening the bond adjacent to the carboxyl group.

Study of calcium-containing compounds as catalysts for the esterification of glycerol with higher carboxylic acids

Objectives. To investigate the catalytic activity of calcium-containing basic catalysts for the esterification of glycerol with higher carboxylic acids in order to develop a low-waste technology for the production of multifunctional additives, as well as to assess the possibility of using the reaction products for the processing of polyvinyl chloride.Methods. The consumption of oleic acid during synthesis was monitored using a titrimetric method of analysis with visual indication. The structure of the synthesized calcium-containing catalysts was confirmed by infrared spectroscopy; elemental analysis was additionally performed for calcium glyceroxide. Quantitative and qualitative analyses of the resulting mixtures of oleic acid glycerides were carried out using chromato-mass spectrometry. A sample of a multifunctional additive was tested in a model formulation of a medical plastic compound based on polyvinyl chloride.Results. It is shown that the catalytic activity of calcium derivatives in the reaction of esterification of glycerol with higher carboxylic acids increases in the series СаО < Са(ОН)2 < Ca(C17H33COO)2 < Ca(C2H5O)2 < Ca(C4H9O)2 < Ca(C3H7O3)2, while the use of calcium glyceroxide as a catalyst in an amount from 1 to 6 mol % increases the conversion of carboxylic acid from 58 to 86% in 10 h of synthesis. However, varying the amount of calcium glyceroxide from 1.5 to 6 mol % results in no observed changes in the conversion of carboxylic acid. The multifunctional additive obtained by selecting calcium glyceroxide as a catalyst has a thermally stabilizing and plasticizing effect on the polymer composition. The introduction of the developed additive into the formulation of a polyvinyl chloride composition for medical purposes reduces the processing torque and time to reach the dry point. By combining these factors, energy costs during production were reduced by more than 11% compared to the control composition.Conclusions. It is established that calcium alcoholates catalyze the reaction of esterification of glycerol with oleic (or higher) acid to increase the conversion of the initial substances and selectivity for the formation of monoglycerides as compared with calcium oxide, hydroxide, and oleate. By optimizing the ratio of glycerol : oleic acid : calcium glyceroxide at 1 : 1 : 0.015, the maximum conversion of oleic acid of up to 86% in 10 h was obtained via synthesis. The proposed method for esterification of glycerol with higher carboxylic acids in the presence of a calcium-containing catalyst avoids the stage of purification from the catalyst to obtain a composition with multifunctional additive properties for the processing of polyvinyl chloride.

A Photochemical Protocol for the Synthesis of Weinreb and Morpholine Amides from Carboxylic Acids Cover Feature: (Eur. J. Org. Chem. 24/2023)

The Cover Feature illustrates the photochemical conversion of carboxylic acids to Weinreb and morpholine amides. Sunlight or LED 370 nm irradiation mediates the direct coupling of carboxylic acids to N,O-dimethylhydroxylamine or morpholine in the presence of 4-dimethylaminopyridine and bromotrichloromethane, providing the corresponding amides in satisfactory to high yields. More information can be found in the Research Article by C. G. Kokotos, G. Kokotos et al.

Isothiouronium-Mediated Conversion of Carboxylic Acids to Cyanomethyl Thioesters.

We report the development of an isothiouronium salt as a reagent for the operationally simple synthesis of cyanomethyl thioesters with high functional group tolerance and avoiding the use of thiols. Additionally, we show that the products can be engaged in amide synthesis in either a two-step or one-pot fashion.

Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids.

Triazoles have major roles in chemistry, medicine, and materials science, as centrally important heterocyclic motifs and bioisosteric replacements for amides, carboxylic acids, and other carbonyl groups, as well as some of the most widely used linkers in click chemistry. Yet, the chemical space and molecular diversity of triazoles remains limited by the accessibility of synthetically challenging organoazides, thereby requiring preinstallation of the azide precursors and restricting triazole applications. We report herein a photocatalytic, tricomponent decarboxylative triazolation reaction that for the first time enables direct conversion of carboxylic acids to triazoles in a single-step, triple catalytic coupling with alkynes and a simple azide reagent. Data-guided inquiry of the accessible chemical space of decarboxylative triazolation indicates that the transformation can improve access to the structural diversity and molecular complexity of triazoles. Experimental studies demonstrate a broad scope of the synthetic method that includes a variety of carboxylic acid, polymer, and peptide substrates. When performed in the absence of alkynes, the reaction can also be used to access organoazides, thereby obviating preactivation and specialized azide reagents and providing a two-pronged approach to C-N bond-forming decarboxylative functional group interconversions.

Visible-light-driven direct decarboxylative carbonylation of carboxylic acids using acridine photocatalysis in oxygen-liquid flow

Photocatalytic direct decarboxylative carbonylation of ubiquitous carboxylic acids is a promising strategy to obtain highly versatile ketone building blocks, but metal-free and efficient conversions are still lacking. Here, density functional theory calculations are used to guide the experimental screening of catalysts, highlighting the potential influence of frontier molecular orbital energy levels on the catalytic process and revealing an acridine photocatalyst capable of realizing value-added conversion of carboxylic acid at room temperature under visible light with excellent performance. The possible mechanism for this conversion was elucidated in depth by combining study of the excited state behavior of the photosensitizer and the results of detection experiments for radicals. Theoretical calculations and mechanistic studies further disclose the kinetically rate-limiting role of oxygen, including its participation in the formation of superoxide radicals for carbonylation and as an electron trapping agent for catalyst cycling. Based on these findings, a flow microreactor platform was ingeniously built to achieve previously inaccessible photocatalytic decarboxylative carbonylation promoted by acridine in concert with oxygen. Interestingly, the gas–liquid segmented microflow is found to enable a significant acceleration (from 14 to 2 h) and higher yield compared to the batch counterpart, resulting in a high space–time yield of 137.4 g/L d-1 for this transformation, which far exceeds the reported values. This study underscores the feasibility of broadening the competence of acridine photocatalysis through the involvement of kinetically adapted oxygen, thus enabling substitution of metal-dependent photocatalysis and even more efficient and high-yield decarboxylative carbonylation of carboxylic acids.

A Simple and Modified One Pot Conversion of Carboxylic Acid to Ketone

Background: Ketone is one of the important functional groups in synthetic chemistry. For this reason, organic chemists focused on the synthesis of ketone starting from various functionalities since nineties. One of the method deals with the conversion of carboxylic acids to ketones in a one pot manner. We have recently reported a one pot transformation of carboxylic acid to ketone using TsCl or MsCl as an activator of carboxylc acid. In our previous reports, two equivalents of organometallic reagent have been used which may not be useful in medicinal chemistry. In this report, we have developed an alternative process for the transformation where only one equivalent of organometallic reagent has been employed. Objective: In present scenario, we are interested to develop a process for the transformation of carboxylic acid to ketone using one equivalent of an organometallic reagent. Methods: A carboxylic acid reacted with tosyl chloride in the presence of a sodium hydride to form a mixed anhydride. Here, the acidic proton was removed from the reaction mixture as hydrogen gas. This mixed anhydride was then treated with one equivalent of an organomagnesium reagent at -30°C to obtain the desired ketone. Results: Following the optimum conditions, a few commercially available carboxylic acids were treated with TsCl, followed by the treatment of phenyl magnesium and methyl magnesium bromide to obtain phenyl and methyl ketones, respectively, in good to excellent yields. Conclusion: A simple and modified one pot method for the conversion of carboxylic acids to ketone has been reported. In this developed process, one equivalent of the organomagnesium reagent has been used to obtain the desired ketone under the optimized reaction conditions.