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Synthesis Of Ketones From Carboxylic Acids

Reactions Of Carboxylic Acids

Reactions Of Carboxylic Acids

Reactions with Organolithium Compounds and Metal Hydrides Carboxylic acids are both Brønsted acids and Lewis acids. Their Lewis acid qualities may be attributed not only to the acidic proton, but also to the electrophilic carbonyl carbon, as they are both able to act as an electron acceptor. However, if a carboxylic acid is treated with an organolithium compound, an acid-base reaction first takes place. In such a reaction, the acidic proton is abstracted by the organolithium compound's alkyl or aryl anion, as alkyl and aryl anions are extremely strong bases. Nevertheless, alkyl and aryl anions are also efficient nucleophiles. As a result, the carbonyl carbon of the carboxylate anion which is formed in the first reaction step is nucleophilically attacked by an additional alkyl or aryl anion. The result of a subsequent hydrolysis is the protonation of the dianion. This yields a geminal diol and lithium hydroxide. The geminal diol represents a ketone's hydrate. Thus, it spontaneously eliminates water to yield the ketone. The reaction may be carried out with primary, secondary, and tertiary alkyllithium compounds, as well as with aryllithium compounds. In order to obtain a ketone in this reaction, two equivalents of the organolithium compound to one equivalent of carboxylic acid must be applied, as the first equivalent is consumed by the acid-base reaction which cannot be prevented. Due to the negative charge of the carboxylate anion, the electrophilicity of a ketone's carbonyl carbon is comparatively higher. Nevertheless, the ketone does not react with the organolithium compound, as it is not formed until the workup with water through which the remaining organolithium compound is also hydrolyzed. In contrast with lithium aluminum hydride, carboxylic acids are reduced to t Continue reading >>

Organic Chemistry/ketones And Aldehydes

Organic Chemistry/ketones And Aldehydes

Aldehydes () and ketones () are both carbonyl compounds. They are organic compounds in which the carbonyl carbon is connected to C or H atoms on either side. An aldehyde has one or both vacancies of the carbonyl carbon satisfied by a H atom, while a ketone has both its vacancies satisfied by carbon. 3 Preparing Aldehydes and Ketones Ketones are named by replacing the -e in the alkane name with -one. The carbon chain is numbered so that the ketone carbon, called the carbonyl group, gets the lowest number. For example, would be named 2-butanone because the root structure is butane and the ketone group is on the number two carbon. Alternatively, functional class nomenclature of ketones is also recognized by IUPAC, which is done by naming the substituents attached to the carbonyl group in alphabetical order, ending with the word ketone. The above example of 2-butanone can also be named ethyl methyl ketone using this method. If two ketone groups are on the same structure, the ending -dione would be added to the alkane name, such as heptane-2,5-dione. Aldehydes replace the -e ending of an alkane with -al for an aldehyde. Since an aldehyde is always at the carbon that is numbered one, a number designation is not needed. For example, the aldehyde of pentane would simply be pentanal. The -CH=O group of aldehydes is known as a formyl group. When a formyl group is attached to a ring, the ring name is followed by the suffix "carbaldehyde". For example, a hexane ring with a formyl group is named cyclohexanecarbaldehyde. Aldehyde and ketone polarity is characterized by the high dipole moments of their carbonyl group, which makes them rather polar molecules. They are more polar than alkenes and ethers, though because they lack hydrogen, they cannot participate in hydrogen bonding like Continue reading >>

One-pot Synthesis Of Aldehydes Or Ketones From Carboxylic Acids Via In Situ Generation Of Weinreb Amides Using The Deoxo-fluor Reagent

One-pot Synthesis Of Aldehydes Or Ketones From Carboxylic Acids Via In Situ Generation Of Weinreb Amides Using The Deoxo-fluor Reagent

A one-pot, high yield conversion of carboxylic acids to the corresponding aldehydes and ketones is described. The highlight of this methodology is the in situ generation of Weinreb amides with the Deoxo-Fluor reagent, which undergo nucleophilic reaction with DIBAL-H and Grignard reagents. Continue reading >>

Preparation Of Ketones From The Reaction Of Organolithium Reagents With Carboxylic Acids

Preparation Of Ketones From The Reaction Of Organolithium Reagents With Carboxylic Acids

Abstract The reaction of organolithium reagents and carboxylic acids constitutes a simple general method for the synthesis of ketones. This preparative route is the method of choice for direct conversion of carboxylic acid to ketones. It is the purpose of this chapter to evaluate critically the scope and limitations of this reaction and to recommend optimal conditions for its applications. The reaction of organolithium reagents with carboxylic acid is limited to the preparation of acyclic ketones. Although the objective of this reaction, the formation of unsymmetrical ketones, the method is clearly applicable to the synthesis of symmetrical ketones. Two different routes are possible and are discussed. To date, the reaction has been applied only to the preparation of monoketones. Continue reading >>

Synthesis Of Ketones

Synthesis Of Ketones

Like aldehydes, ketones can be prepared in a number of ways. The following sections detail some of the more common preparation methods: the oxidation of secondary alcohols, the hydration of alkynes, the ozonolysis of alkenes, Friedel‐Crafts acylation, the use of lithium dialkylcuprates, and the use of a Grignard reagent. The oxidation of secondary alcohols to ketones may be carried out using strong oxidizing agents, because further oxidation of a ketone occurs with great difficulty. Normal oxidizing agents include potassium dichromate (K 2Cr 2O 7) and chromic acid (H 2CrO 4). The conversion of 2‐propanol to 2‐propanone illustrates the oxidation of a secondary alcohol. The addition of water to an alkyne leads to the formation of an unstable vinyl alcohol. These unstable materials undergo keto‐enol tautomerization to form ketones. The hydration of propyne forms 2‐propanone, as the following figure illustrates. When one or both alkene carbons contain two alkyl groups, ozonolysis generates one or two ketones. The ozonolysis of 1,2‐dimethyl propene produces both 2‐propanone (a ketone) and ethanal (an aldehyde). Friedel‐Crafts acylations are used to prepare aromatic ketones. The preparation of acetophenone from benzene and acetyl chloride is a typical Friedel‐Crafts acylation. The addition of a lithium dialkylcuprate (Gilman reagent) to an acyl chloride at low temperatures produces a ketone. This method produces a good yield of acetophenone. Hydrolysis of the salt formed by reacting a Grignard reagent with a nitrile produces good ketone yields. For example, you can prepare acetone by reacting the Grignard reagent methyl magnesium bromide (CH 3MgBr) with methyl nitrile (CH 3C&tbond;N). Continue reading >>

Aldehydes, Ketones, Carboxylic Acids, And Esters

Aldehydes, Ketones, Carboxylic Acids, And Esters

Learning Objectives By the end of this section, you will be able to: Describe the structure and properties of aldehydes, ketones, carboxylic acids and esters Another class of organic molecules contains a carbon atom connected to an oxygen atom by a double bond, commonly called a carbonyl group. The trigonal planar carbon in the carbonyl group can attach to two other substituents leading to several subfamilies (aldehydes, ketones, carboxylic acids and esters) described in this section. Aldehydes and Ketones Both aldehydes and ketones contain a carbonyl group, a functional group with a carbon-oxygen double bond. The names for aldehyde and ketone compounds are derived using similar nomenclature rules as for alkanes and alcohols, and include the class-identifying suffixes –al and –one, respectively: In an aldehyde, the carbonyl group is bonded to at least one hydrogen atom. In a ketone, the carbonyl group is bonded to two carbon atoms: In both aldehydes and ketones, the geometry around the carbon atom in the carbonyl group is trigonal planar; the carbon atom exhibits sp2 hybridization. Two of the sp2 orbitals on the carbon atom in the carbonyl group are used to form σ bonds to the other carbon or hydrogen atoms in a molecule. The remaining sp2 hybrid orbital forms a σ bond to the oxygen atom. The unhybridized p orbital on the carbon atom in the carbonyl group overlaps a p orbital on the oxygen atom to form the π bond in the double bond. Like the C=O bond in carbon dioxide, the C=O bond of a carbonyl group is polar (recall that oxygen is significantly more electronegative than carbon, and the shared electrons are pulled toward the oxygen atom and away from the carbon atom). Many of the reactions of aldehydes and ketones start with the reaction between a Lewis base and Continue reading >>

Synthesis Of Aldehydes And Ketones

Synthesis Of Aldehydes And Ketones

Name Reactions Fukuyama Coupling Grignard Reaction Grignard Reaction Seebach Umpolung Stetter Synthesis Recent Literature Carboxylic acids were converted directly in good yields into ketones using excess alkyl cyanocuprates (R2CuLi•LiCN). A substrate with a stereocenter α to the carboxylic acid was converted with very little loss of enantiomeric purity. A variety of functional groups were tolerated including aryl bromides. This direct transformation involves a relatively stable copper ketal tetrahedral intermediate. D. T Genna, G. H. Posner, Org. Lett., 2011, 13, 5358-5361. Unsymmetrical dialkyl ketones can be prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. Various functional groups are tolerated, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. A. C. Wotal, D. J. Weix, Org. Lett., 2012, 14, 1363-1365. N-acylazetidines are bench-stable, readily available amide acylating reagents, in which the reactivity is controlled by amide pyramidalization and strain of the four-membered ring. A general and highly chemoselective synthesis of ketones by the addition of organometallics to N-acylazetidines via stable tetrahedral intermediates offers wide substrate scope and exquisite selectivity for the ketone products. C. Liu, M. Achtenhagen, M. Szostak, Org. Lett., 2016, 18, 2375-2378. A range of unsymmetrical ketones has been prepared in good yields from aldehydes in one simple synthetic operation by addition of organolithium compounds followed by an oxidation using N-tert-butylphenylsulfinimidoyl chloride. J. J. Crawford, K. W. Hederson, W. J. Kerr, Org. Lett., 2006, 8, 5073-5076. Visible light Continue reading >>

Aldehyde, Ketones And Carboxylic Acids

Aldehyde, Ketones And Carboxylic Acids

Aldehyde and  Ketones Preparation of Aldehydes  a. Oxidation of primary alcohols a) Oxidation of Secondary alcohols: a)  Aldol condensation Aldehydes and ketones having alpha hydrogen atom: Aldehydes and ketones having  no alpha hydrogen atom:   Esters having a-hydrogen on treatment with a strong base e.g. C2H5ONa. Undergo self condensation to produce b-keto esters. This reaction is Claisen Condensation. d)   Reformatsky Reaction This is the reaction of a-haloester, usually an a-bromoester with an aldehyde or ketone in the presence of Zinc metal to produce b-hydroxyester. e) Pinacol-pinacolone Rearrangement The acid catalysed rearrangement of 1,2 diols (Vicinal diols) to aldehydes or ketones with the elimination of water is known as pinacol pinacolone rearrangement. Aldehydes and Ketones react with phosphorus Ylides to yield alkenes and triphenyl phosphine oxide. An Ylide is a neutral molecule having a negative carbon adjacent to a positive hetero atom. Phosphorus ylides are also called phosphoranes. Preparation of Ylides Above things happens in BVO (Bayer Villiger oxidation). Reagents are either per acetic acid or perbenzoic acid or pertrifluoroacetic acid or permonosulphuric acid. e)   Addition of cyanide h)   Addition of Alcohols; Acetal Formation In H3O+, RCHO is regenerated because acetals undergo acid catalyzed cleavage much more easily than do ethers. Since acetals are stable in neutral or basic media, they are used to protect the – CH = O group. All aldehydes can be made to undergo the Cannizzaro reaction by treatment with aluminium ethoxide. Under these conditions the acids and alcohols are combined as the ester, and the reaction is then known as the Tischenko reaction; eg, acetaldehyde gives ethyl acetate, and propionaldehyde gives propyl propi Continue reading >>

Synthesis Of Carboxylic Acids

Synthesis Of Carboxylic Acids

Most of the methods for the synthesis of carboxylic acids can be put into one of two categories: (1) hydrolysis of acid derivatives and (2) oxidation of various compounds. All acid derivatives can be hydrolyzed (cleaved by water) to yield carboxylic acids; the conditions required range from mild to severe, depending on the compound involved. The easiest acid derivatives to hydrolyze are acyl chlorides, which require only the addition of water. Carboxylic acid salts are converted to the corresponding acids instantaneously at room temperature simply on treatment with water and a strong acid such as hydrochloric acid (shown as H+ in the equations above). Carboxylic esters, nitriles, and amides are less reactive and typically must be heated with water and a strong acid or base to give the corresponding carboxylic acid. If a base is used, a salt is formed instead of the carboxylic acid, but the salt is easily converted to the acid by treatment with hydrochloric acid. Of these three types of acid derivatives, amides are the least reactive and require the most vigorous treatment (i.e., higher temperatures and more prolonged heating). Under milder conditions, nitriles can also be partially hydrolyzed, yielding amides: RCN → RCONH2. The oxidation of primary alcohols is a common method for the synthesis of carboxylic acids: RCH2OH → RCOOH. This requires a strong oxidizing agent, the most common being chromic acid (H2CrO4), potassium permanganate (KMnO4), and nitric acid (HNO3). Aldehydes are oxidized to carboxylic acids more easily (by many oxidizing agents), but this is not often useful, because the aldehydes are usually less available than the corresponding acids. Also important is the oxidation of alkyl side chains of aromatic rings by strong oxidizing agents such as chrom Continue reading >>

Secondary And Tertiary Alkyl Ketones From Carboxylic Acid Chlorides And Lithium Phenylthio(alkyl)cuprate Reagents:

Secondary And Tertiary Alkyl Ketones From Carboxylic Acid Chlorides And Lithium Phenylthio(alkyl)cuprate Reagents:

A. Lithium phenylthio(tert-butyl)cuprate. A dry, 200-ml., round-bottomed flask is fitted with a magnetic stirring bar and a 100-ml., pressure-equalizing dropping funnel, the top of which is connected to a nitrogen inlet. After the apparatus has been flushed with nitrogen, 50 ml. of 1.60 M (0.080 mole) n-butyllithium (Note 1) solution is placed in the flask and cooled with an ice bath. Under a nitrogen atmosphere, a solution of 8.81 g. (0.0801 mole) of freshly distilled thiophenol (Note 2) in 30 ml. of anhydrous tetrahydrofuran (Note 3) is added dropwise to the cooled, stirred solution. An aliquot of the resulting solution (Note 4) is standardized by quenching in water, followed by titration with 0.10 N hydrochloric acid to a green end point with a bromocresol indicator. The concentration of lithium thiophenoxide prepared in this manner is typically 1.0 M. A dry, 250-ml., three-necked round-bottomed flask is equipped with a sealed mechanical stirrer (Note 5), a glass stopper, and a rubber septum through which are inserted hypodermic needles used to evacuate the flask and to admit nitrogen. After the apparatus has been flushed with nitrogen, 4.19 g. (0.0220 mole) of purified copper(I) iodide (Note 6) is added, and while warming with a flame, the apparatus is evacuated, then refilled with nitrogen. After this procedure has been performed twice, the flask is allowed to cool, the stopper is replaced with a thermometer, and 45 ml. of anhydrous tetrahydrofuran is added (Note 3) with a hypodermic syringe. With continuous stirring, 22 ml. of 1.0 M (0.022 mole) lithium thiophenoxide solution is added with a syringe to the slurry of copper(I) iodide. After 5 minutes, the resulting yellow solution is cooled, with continuous stirring, to −65° with an acetone–dry ice cooling bat Continue reading >>

Making Carboxylic Acids

Making Carboxylic Acids

This page looks at ways of making carboxylic acids in the lab by the oxidation of primary alcohols or aldehydes, and by the hydrolysis of nitriles. Note: If you are interested in the preparation of benzoic acid (benzenecarboxylic acid) you will find it described in the section on arenes (aromatic hydrocarbons like benzene and methylbenzene). Benzoic acid is normally made by oxidising hydrocarbon side chains attached to a benzene ring. This is described towards the bottom of the page you will get to by following this link. If you choose to follow this link, use the BACK button on your browser to return to this page. Making carboxylic acids by oxidising primary alcohols or aldehydes Chemistry of the reactions Primary alcohols and aldehydes are normally oxidised to carboxylic acids using potassium dichromate(VI) solution in the presence of dilute sulphuric acid. During the reaction, the potassium dichromate(VI) solution turns from orange to green. The potassium dichromate(VI) can just as well be replaced with sodium dichromate(VI). Because what matters is the dichromate(VI) ion, all the equations and colour changes would be identical. Primary alcohols are oxidised to carboxylic acids in two stages - first to an aldehyde and then to the acid. We often use simplified versions of these equations using "[O]" to represent oxygen from the oxidising agent. The formation of the aldehyde is shown by the simplified equation: "R" is a hydrogen atom or a hydrocarbon group such as an alkyl group. Note: Although "R" can in principle be a hydrogen atom, in practice if it is a hydrogen, the oxidation eventually goes all the way to carbon dioxide and water rather than stopping at methanoic acid. Unlike most other carboxylic acids, methanoic acid is very easily oxidised. The aldehyde is the Continue reading >>

Aldehydes And Ketones

Aldehydes And Ketones

Nature of The Carbonyl Group The carbonyl group consists of a carbon double bonded to an oxygen. >C=O Similar to alkenes - >C=C< >C=O - carbon is sp2 hybridized - 120o bond angles - planar about the double bond Polar d+ d- + - >C==O « >C—O - C is electrophilic - O is nucleophilic Classification of Carbonyl Compounds by R- and Y- All carbonyl compounds contain an acyl group , RCO- , bonded to another residue, -Y. R- = alkyl, aryl alkenyl or alkynyl Y- = C, H, O, N, S, halogen, or other atom Aldehyde: Y = H Ketone: Y = R group Classification of Carbonyl Compounds by Rxn Types A. Y = non-leaving groups. (e.g. aldehydes and ketones) B. Y = leaving groups. (e.g. -OR, -NR2, -Cl) Aldehydes: R-CHO Ar-CHO Ketones: R-COR' Ar-COR Ar-COAr' Aldehyde Nomenclature 1. Identify the longest continuous chain of carbons with the carbonyl carbon as part of the chain. 2. Assign priority (number the carbon chain) so that the carbonyl (acyl) carbon is always #1. In nomenclature the carbonyl has higher priority than the hydroxyl group. 3. Locate and identify alphabetically the branched groups by prefixing the carbon number it is attached to. If more than one of the same type of branched group is involved use the Greek prefixes di for 2, tri for three, etc. 4. After identifying the name, number and location of each branched group, use the alkane name corresponding to the number of carbons in the continuous chain. 5. Drop the "e" and add the characteristic IUPAC ending for all aldehydes, "al". 6. Alkenals involving Pi bonding will require that the Pi bond is located but the ending will still be "al". 7. If the -CHO group is attached to a ring the suffix -carbaldehyde is used. Systematic name (common name) Systematic name (common name) Methanal (formaldehyde) 3-bromo-5-methylhexanal Ethanal (ac Continue reading >>

On The Reaction Between Methyllithium And Carboxylic Acids

On The Reaction Between Methyllithium And Carboxylic Acids

In 1933, Gilman showed that on carbonation phenyllithium yielded 70% benzophenone and no benzoic acid, which is the main product on carbonation of the corresponding magnesium compound. They found that the reason for the high yield of ketone was the higher reactivity of the organolithium compound. If an aryllithium compound was allowed to react with carbon dioxide at temperatures between -50°C and -80°C the following reaction occurred: RLi + CO2 RCOOLi At a higher temperature (room temperature) another reaction took place. To the lithium salt of ArCOOH was added one mole of aryllithium, and a dilithium salt of a dihydroxymethane was obtained, which on hydrolysis yielded a ketone in accordance with the following general reaction: Only in one case, hitherto, has any comparison been made between the use of the free acid or its lithium salt: In the case of benzophenone Gilman and van Ess have made two syntheses. One started with the lithium benzoate, which was allowed to react with one mole of phenyllithium, and was found to give a 70% yield of ketone and no tertiary alcohol; the second experiment started with benzoic acid and two moles of phenyllithium and yielded 37.2% of ketone and 14.1% of triphenylcarbinol. Two possible explanations are given for the formation of the tertiary alcohol. The first is that benzoic acid is dehydrated by phenyllithium to give benzoic anhydride. This would react with one mole of phenyllithium to give lithium benzoate and "free" benzophenone, which would enter the ordinary reaction of a ketone yielding triphenylcarbinol: 2 C6H5COOH + 2 C6H5Li (C6H5CO)2O (C6H5CO)2O + C6H5Li (C6H5)2CO + C6H5COOLi (C6H5)2CO + C6H5Li (C6H5)3COLi -> (C6H5)3COH Another explanation is suggested, in which the phenyllithium is supposed to be added directly to the carb Continue reading >>

Synthesis Of Aldehydes, Ketones, And Carboxylic Acids From Lower Carbonyl Compounds By C-c Coupling Reactions

Synthesis Of Aldehydes, Ketones, And Carboxylic Acids From Lower Carbonyl Compounds By C-c Coupling Reactions

© Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published therein, is legally protected by copyright for the duration of the copyright period. Any use, exploitation or commercialization outside the narrow limits set by copyright legislation, without the publisher's consent, is illegal and liable to criminal prosecution. This applies in particular to photostat reproduction, copying, cyclostyling, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage. The methodology for the preparation of aldehydes, ketones, and carboxylic acids or their derivatives from lower carbonyl compounds by carbon-carbon bond forming reactions is reviewed. The material is presented according to the number of carbon atoms (1, 2, 3, or 4) that separate the carbonyl or acyl group, added during the carbon-carbon bond formation, from the original electrophilic center. 1. Introduction 2. Aldehydes and Ketones by One Carbon Elongations 2.1. Addition of Masked Acyl Anions 2.2. Reductive Nucleophilic Acylation 2.3. Nucleophilic Acylation Followed by Additional Carbonyl Elaboration 3. Carboxylic Acids or Their Derivatives by One Carbon Elongations 3.1. Addition of Masked Carboxyl Anions 3.2. Reductive Nucleophilic Carboxylation 3.3. Nucleophilic Carboxylation Followed by Additional Carbonyl Elaboration 4. Aldehydes and Ketones by Two Carbon Elongations 4.1. Aldol Condensation and Related Reactions 4.2. Wittig and Other Olefination Reactions 5. Carboxylic Acids or Their Derivatives by Two Carbon Elongations 5.1. Addition of Enolates of Carboxylic Acid Derivatives 5.2. Reaction with Ketene and Related Compounds 5.3. Wittig and Ot Continue reading >>

Ketone

Ketone

Not to be confused with ketone bodies. Ketone group Acetone In chemistry, a ketone (alkanone) /ˈkiːtoʊn/ is an organic compound with the structure RC(=O)R', where R and R' can be a variety of carbon-containing substituents. Ketones and aldehydes are simple compounds that contain a carbonyl group (a carbon-oxygen double bond). They are considered "simple" because they do not have reactive groups like −OH or −Cl attached directly to the carbon atom in the carbonyl group, as in carboxylic acids containing −COOH.[1] Many ketones are known and many are of great importance in industry and in biology. Examples include many sugars (ketoses) and the industrial solvent acetone, which is the smallest ketone. Nomenclature and etymology[edit] The word ketone is derived from Aketon, an old German word for acetone.[2][3] According to the rules of IUPAC nomenclature, ketones are named by changing the suffix -ane of the parent alkane to -anone. The position of the carbonyl group is usually denoted by a number. For the most important ketones, however, traditional nonsystematic names are still generally used, for example acetone and benzophenone. These nonsystematic names are considered retained IUPAC names,[4] although some introductory chemistry textbooks use systematic names such as "2-propanone" or "propan-2-one" for the simplest ketone (CH3−CO−CH3) instead of "acetone". The common names of ketones are obtained by writing separately the names of the two alkyl groups attached to the carbonyl group, followed by "ketone" as a separate word. The names of the alkyl groups are written alphabetically. When the two alkyl groups are the same, the prefix di- is added before the name of alkyl group. The positions of other groups are indicated by Greek letters, the α-carbon being th Continue reading >>

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