Synthesis Of Ketones By Cleavage Of Alkenes
Name Reactions Recent Literature The OsO4-catalyzed direct oxidation of olefins via the carbon-carbon cleavage of an osmate ester by the action of oxone allows the preparation of ketones or carboxylic acids in high yields. This method should be applicable as an alternative to ozonolysis. B. R. Travis, R. S. Narayan, B. Borhan, J. Am. Chem. Soc., 2002, 124, 3824-3825. N-hydroxyphthalimide (NHPI) catalyzes a metal-free, aerobic oxidative cleavage of olefins. This methodology avoids the use of toxic metals or overstoichiometric amounts of traditional oxidants, showing good economical and environmental advantages. Based on the experimental observations, a plausible mechanism is proposed. R. Lin, F. Chen, N. Jiao, Org. Lett., 2012, 14, 4158-4161. A mild and operationally simple protocol for the selective aerobic oxidation of aromatic olefins to carbonyl compounds is catalyzed by a Fe(III) species bearing a pyridine bisimidazoline ligand at 1 atm of O2. The method cleaves α- and β-substituted styrenes to afford benzaldehydes and aromatic ketones in high yields with excellent chemoselectivity and very good functional group tolerance. A. Gonzalez-de-Castro, J. Xiao, J. Am. Chem. Soc., 2015, 137, 8206-8218. In a 2,2-azobis(isobutyronitrile)-catalyzed oxidative cleavage of gem-disubstituted alkenes with molecular oxygen as the oxidant, carbonyl compounds were obtained as the desired products in high yield under mild conditions. G.-Z. Wang, X.-L. Li, J.-J. Dai, H.-J. Xu, J. Org. Chem., 2014, 79, 7220-7225. A gold(I)-catalyzed oxidative cleavage of alkenes with tert-butyl hydrogenperoxide (TBHP) as the oxidant in the presence of neocuproine afforded ketones or aldehydes as products. D. Xing, B. Guan, G. Cai, Z. Fang, L. Yang, Z. Shi, Org. Lett., 2006, 8, 693-696. Specific oxidati Continue reading >>
Synthesis Of Ketones By Oxidation Of Alkenes
Name Reactions Recent Literature The synergistic effect of photocatalysis and proton-reduction catalysis enables an unprecedented dehydrogenative oxygenation of β-alkyl styrenes and their derivatives with water under external-oxidant-free conditions. This dual catalytic system possesses the single anti-Markovnikov selectivity due to the property of the visible-light-induced alkene radical cation intermediate. G. Zhang, X. Hu, C.-W. Chiang, H. Yi, P. Pei, A. K. Singh, A. Lei, J. Am. Chem. Soc., 2016, 138, 12037-12040. Utilizing the full potential of IBX, a mild, selective, and facile method enables a direct conversion of olefins into the corresponding α-bromo ketones in the presence of 1.1 equivalents each of o-iodoxybenzoic acid and tetraethylammonium bromide. S. S. Deshmukh, K. H. Chaudhari, K. G. Akamanchi, Synlett, 2011, 81-83. In a Co-catalyzed reaction for the construction of 1,4-dicarbonyls, a cascade organocobalt addition/trapping/Kornblum-DeLaMare rearrangement were involved. The reaction offers easy availability of starting materials, wide substrate scope, high functionality tolerance, and operational simplicity. F. Zhang, P. Du, J. Chen, H. Wang, Q. Luo, X. Wan, Org. Lett., 2014, 16, 1932-1935. Oxidative ring expansion of methylenecyclopropanes with CAN under oxygen atmosphere was investigated. A facile conversion affording 2,2-diarylcyclobutanones occurred in good yields. V. Nair, T. D. Suja, K. Mohanan, Synthesis, 2006, 2531-2534. A practical and environmentally friendly method for the oxidative rearrangement of five- and six-membered cyclic tertiary allylic alcohols to α,β-unsaturated β-disubstituted ketones by IBX in DMSO is described. Several conventional protecting groups (e.g., Ac, MOM, and TBDPS) are tolerated. M. Shibuya, S. Ito, M. Takahashi, Y. Continue reading >>
Catalytic Addition Of Simple Alkenes To Carbonyl Compounds Using Group 10 Metals
Go to: 1 Introduction Functionalization of simple alkenes has long been a focus in organic chemistry, largely because alkenes are one of the most readily available classes of functional groups.1 Several indispensable catalytic transformations utilize olefins, such as Ziegler-Natta polymerization, the Wacker oxidation, hydroformylation, epoxidation, hydrometallation, and dihydroxylation, and thereby provide access to several important classes of other functional groups.2–4 Similarly important technologies are those that functionalize olefins while leaving the olefin intact, such as olefin cross-metathesis and the Heck reaction.5,6 The resulting functionalized alkenes serve as versatile building blocks for subsequent manipulations. Historically, the most direct methods for the synthesis of allylic and homoallylic alcohols from alkenes and carbonyl compounds are the Prins reaction and carbonyl-ene reaction (Scheme 1).7,8 These reactions generally form a new carbon–carbon bond at the less substituted carbon of the alkene. Typically, electron-rich alkenes, such as 1,1-disubstituted or trisubstituted olefins, react effectively with small and electron-deficient enophiles, including formaldehyde and glyoxylates. These processes proceed with heating and typically benefit from significant rate enhancement under the action of Lewis acid catalysts. Considerably less attention has been paid to extending the substrate scope to include electron-rich and sterically demanding aldehydes or less nucleophilic alkenes such as α-olefins.9–12 The typical carbonyl used in the intermolecular Prins reaction to make allylic alcohols is also largely limited to formaldehyde. In short, these traditional technologies are effective for only a small subset of the plethora of possible coupling pa Continue reading >>
Nucleophilic Addition
Reactions of aldehydes and ketones: oxidation reduction nucleophilic addition Aldehydes are easily oxidized, ketones are not. Aldehydes are more reactive in nucleophilic additions than ketones. alkane alcohol aldehyde ketone carboxylic acid oxidation reduction reduction addition product nucleophilic addition nucleophilic addition to carbonyl: Mechanism: nucleophilic addition to carbonyl 1) 2) Mechanism: nucleophilic addition to carbonyl, acid catalyzed 1) 2) 3) Aldehydes & ketones, reactions: Oxidation Reduction Addition of cyanide Addition of derivatives of ammonia Addition of alcohols Cannizzaro reaction Addition of Grignard reagents 8) (Alpha-halogenation of ketones) 9) (Addition of carbanions) 1) Oxidation Aldehydes (very easily oxidized!) CH3CH2CH2CH=O + KMnO4, etc. ïƒ CH3CH2CH2COOH carboxylic acid CH3CH2CH2CH=O + Ag+ ïƒ CH3CH2CH2COO- + Ag Tollen’s test for easily oxidized compounds like aldehydes. (AgNO3, NH4OH(aq)) Silver mirror Cyanohydrins have two functional groups plus one additional carbon. Nitriles can be hydrolyzed to carboxylic acids in acid or base: melting points of derivatives ketones bp semi- 2,4-dinitro- oxime carbazone phenylhydrazone 2-nonanone 195 119 56 acetophenone 202 199 240 60 menthone 209 189 146 59 2-methylacetophenone 214 205 159 61 1-phenyl-2-propanone 216 200 156 70 propiophenone 220 174 191 54 3-methylacetophenone 220 198 207 55 isobutyrophenone 222 181 163 94 Aldehydes & ketones, reactions: Oxidation Reduction Addition of cyanide Addition of derivatives of ammonia Addition of alcohols Cannizzaro reaction Addition of Grignard reagents 8) (Alpha-halogenation of ketones) 9) (Addition of carbanions) “The Grignard Song†(sung to the tune of “America the Beautifulâ€) Harry Wasserman The carbonyl is polarized, th Continue reading >>
Enolates With Aldehydes And Ketones
Mannich Reaction This is a typical example of a Mannich reaction. It involves an enolizable aldehyde or ketone, a secondary amine, formaldehyde as its aqueous solution, and catalytic HCl. The product is an amino-ketone from the addition of one molecule each of formaldehyde and the amine to the ketone. Below are shown the various stages of the Mannich reaction. 'Click' the different stages to view 3D animations of the reactions: Step 1: Imine formation Step 2: Addition of imine salt to ketone The Mannich products can be converted to enones. Enones such as that shown below, with two hydrogen atoms at the end of the double bond are called exo-methylene compounds. Whilst they are very reactive, they cannot easily be made or stored. Click the image to view the 3D animation T. F. Cummings and J. R. Shelton, J. Org. Chem, 1960, 25, 419–423. H. G. O. Alvim, E. N. da Silva Júnior and B. A. D. Neto, RSC Adv., 2014, 4, 54282–54299. 621 Continue reading >>
2 Departamento De Quãmica, Facultad Experimental De Ciencias, Universidad Del Zulia,
Reviews and Accounts ARKIVOC 2013 (i) 396-417 Page 396 © ARKAT-USA, Inc. Reagents for the synthesis of alkenes from carbonyl compounds: applications in the synthesis of terpenoid compounds William J. Vera, 1 Manuel S. Laya, 1 Po S. Poon, 1 Ajoy K. Banerjee, and Elvia V. Cabrera 2 1 Instituto Venezolano de Investigaciones CientÃficas (IVIC), Centro de QuÃmica, Apartado-21827, Caracas-1020A, Venezuela 2 Departamento de QuÃmica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Venezuela Email: [email protected] Abstract The carbon-carbon double bond has been introduced by replacing carbonyl group employing various reagents in several decalones and tetralones. The resulting unsaturated compounds have been utilized for the synthesis of natural products related to diterpenes triptolide, taxodione and sesquiterpenes, herbertene, cuauhtemone, warburganal, drim-8-en-7-one, occidol, mansonone F and biflorine. Keywords: Halide, tosylate, mesylate, alkene, dimethylformamide, 2,4-pentanediol Table of Contents 1. Introduction 2. Reagents for the Conversion of Carbonyl into Alkene 2.1. Lithium bromide (LiBr), lithium carbonate (Li2CO3) and dimethylformamide (DMF) 2.2. Thionyl chloride (SOCl2), phosphorus oxychloride (POCl3) and pyridine 2.3. Acid catalysed (p-toluenesulphonic acid, sulphuric acid, hydrochloric acid) dehydration 2.5. Grignard reagents (MeMgBr, Me2CHMgBr) 2.6. 2,4-Pentanediol and p-toluenesulfonic acid 3. Conclusions 4. Reference Reviews and Accounts ARKIVOC 2013 (i) 396-417 Page 397 © ARKAT-USA, Inc. 1. Introduction The formation of carbon-carbon double bond is of fundamental importance in organic synthesis because it allows the introduction of a wide variety of functional groups. As a result, many reactions and reagents have been develop Continue reading >>
Wacker Oxidation
The Wacker oxidation refers generally to the transformation of a terminal or 1,2-disubstituted alkene to a ketone through the action of catalytic palladium(II), water, and a co-oxidant. Variants of the reaction yield aldehydes, allylic/vinylic ethers, and allylic/vinylic amines. Because of the ease with which terminal alkenes may be prepared and the versatility of the methyl ketone group installed by the reaction, the Wacker oxidation has been employed extensively in organic synthesis.[1] The stoichiometric conversion of ethylene to acetaldehyde by an acidic, aqueous solution of PdCl2 was discovered over a century ago,[2] but fifty years passed between the discovery of this reaction and the development of a catalytic method. In 1959, researchers at Wacker Chemie reported that a similar transformation takes place in an aqueous, acidic solution of catalytic PdCl2 and a stoichiometric amount of CuCl2 through which oxygen is bubbled (Eq. 1).[3] (1) Since this initial report, the Wacker process has been widely applied in organic synthesis and has been extended to other classes of substrates and products. To encourage mixing of the organic reactants with the aqueous phase, a co-solvent is generally employed along with water. Dimethylformamide (DMF) is a common choice; when DMF is used as a co-solvent with a stoichiometric amount of CuCl under balloon pressure of oxygen, the reaction is called the "Tsuji-Wacker oxidation."[4] Applications of the Wacker oxidation to organic synthesis typically involve the installation of a methyl ketone moiety, which may subsequently undergo nucleophilic addition or deprotonation to form an enolate. Mechanism and Stereochemistry The mechanism of the Wacker oxidation has been studied both experimentally and theoretically (Eq. 2). The first step Continue reading >>
Synthesis Of Alkenes From Ketones Via Arylsulphonyl-hydrazones; Mechanistic Views; The Organic Chemistry Notebook Series, A Didactical Approach, N27
ARTÍCULOS ORIGINALES José A. Bravo1*, José L. Vila2 1 Department of Chemistry, Laboratorio de Fitoquímica, Instituto de Investigaciones en Productos Naturales IIPN, Universidad Mayor de San Andrés UMSA, P.O. Box 303, Calle Andrés Bello s/n, Ciudad Universitaria Cota Cota, Phone 59122792238, La Paz, Bolivia, [email protected] *Corresponding author: [email protected] 2Department of Chemistry, Laboratorio de Síntesis y Hemisíntesis, Instituto de Investigaciones en Productos Naturales IIPN, Universidad Mayor de San Andrés UMSA, P.O. Box 303, Calle Andrés Bello s/n, Ciudad Universitaria Cota Cota, Phone 59122795878, La Paz, Bolivia, [email protected] Abstract This is the seventh chapter in the series published by the same authors: "The Organic Chemistry Notebook Series, a Didactical Approach". The aim of this series of studies is to help students to have a graphical view of organic synthesis reactions of diverse nature. Here we describe the mechanistic views of the synthesis of alkenes from ketones via arylsulphonylhydrazones. These methods employ aliphatic and alicyclic ketones with one a-hydrogen, that react along with toluene-p-sulphonylhydrazones and two equivalents of an alkyl-lithium or lithium diisopropylamide. The mechanism views for the transformation of pinacolone into 3,3-dimethyl-1-butene are proposed. The formation of 3-phenylpropene using phenylacetone is explained step by step. An approach is made on the obtaining of alkenes from ketones using derived enol ethers or esters by means of reductive excision or by means of coupling with organocuprates. We have used various series of reactions reviewed by W. Carruthers in 'Some modern methods of organic synthesis', and we have proposed didactical and mechanistic views for them. This theme is included Continue reading >>
Alkenes From Aldehydes And Ketones: Wittig Reaction
The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide (often called a Wittig reagent) to give an alkene and triphenylphosphine oxide. The Wittig reaction was discovered in 1954 by Georg Wittig, for which he was awarded the Nobel Prize in Chemistry in 1979. It is widely used in organic synthesis for the preparation of alkenes. It should not be confused with the Wittig rearrangement. Wittig reactions are most commonly used to couple aldehydes and ketones to singly substituted phosphine ylides. With unstabilised ylides this results in almost exclusively the Z-alkene product. In order to obtain the E-alkene, stabilised ylides are used or unstabilised ylides using the Schlosser modification of the Wittig reaction can be performed. The steric bulk of the ylide 1 influences the stereochemical outcome of nucleophilic addition to give a predominance of the betaine 3 (cf. Bürgi–Dunitz angle). Note that for betaine 3 both R1 and R2 as well as PPh3+ and O− are positioned anti to one another. Carbon-carbon bond rotation gives the betaine 4, which then forms the oxaphosphetane 5. Elimination gives the desired Z-alkene 7 and triphenylphosphine oxide 6. With simple Wittig reagents, the first step occurs easily with both aldehydes and ketones, and the decomposition of the betaine (to form 5) is the rate-determining step. However, with stabilised ylides (where R1 stabilises the negative charge) the first step is the slowest step, so the overall rate of alkene formation decreases and a bigger proportion of the alkene product is the E-isomer. This also explains why stabilised reagents fail to react well with sterically hindered ketones. Mechanistic studies have focused on unstabilized ylides, because the intermedia Continue reading >>
Chelation-assisted Intermolecular Hydroacylation: Direct Synthesis Of Ketone From Aldehyde And 1-alkene
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Chapter 16: Aldehydes And Ketones (carbonyl Compounds)
The Carbonyl Double Bond Both the carbon and oxygen atoms are hybridized sp2, so the system is planar. The three oxygen sp2 AO’s are involved as follows: The two unshared electorn pairs of oxygen occupy two of these AO’s, and the third is involved in sigma bond formation to the carbonyl carbon. The three sp2 AO’s on the carbonyl carbon are involved as follows: One of them is involved in sigma bonding to one of the oxygen sp2 AO’s, and the other two are involved in bonding to the R substituents. The 2pz AO’s on oxygen and the carbonyl carbon are involved in pi overlap, forming a pi bond. The pi BMO, formed by positive overlap of the 2p orbitals, has a larger concentration of electron density on oxygen than carbon, because the electrons in this orbital are drawn to the more electronegative atom, where they are more highly stabilized. This result is reversed in the vacant antibonding MO. As a consequence of the distribution in the BMO, the pi bond (as is the case also with the sigma bond) is highly polar, with the negative end of the dipole on oxygen and the positive end on carbon. We will see that this polarity, which is absent in a carbon-carbon pi bond, has the effect of strongly stabilizing the C=O moiety. Resonance Treatment of the Carbonyl Pi Bond 1.Note that the ionic structure (the one on the right side) has one less covalent bond, but this latter is replaced with an ionic bond (electrostatic bond). 2.This structure is a relatively “good” one, therefore, and contributes extensively to the resonance hybrid, making this bond much more thermodynamically stable than the C=C pi bond, for which the corresponding ionic structure is much less favorable (negative charge is less stable on carbon than on oxygen). 3.The carbonyl carbon therefore has extensive car Continue reading >>
Preparation & Reactions Of Aldehydes And Ketones, Rho & Ror'
A couple of key points: Aldehydes and Ketones both contain a carbonyl group, but are also less reactive than acid chlorides. They do NOT react with organocopper reagents and weak hydride donors (as these weak reagents are involved in their own synthesis). The reactions are addition rather than substitution as there is no leaving group. They have one less bond to an electronegative atom than acid chlorides (no chlorine!). They can be formed through reduction of Acid Chloride: If an aromatic ring is being substituted then we must use friedel crafts acylation. For Acid Chloride to Aldehyde we use Bu3SnH as a source of weak Hydride ions which displace a Cl-. We do not use a more obvious source such as LiAlH4 as this will result in the over reduction of the aldehyde into a primary alcohol. For Acid Chloride to Ketone we use R’2CuLi as a source of nucleophilic R’ group. and via reactions with Alcohols: Simply, Primary alcohols lead to Aldehydes and secondary alcohols lead to Ketones when reacted with PCC. This is oxidation. Testing Laboratory Microbiology - Air Quality - Mold Asbestos - Environmental - Lead emsl.com and finally with Alkanes: Alkanes are just as simple as alcohols – just add O3 then PPh3 for an easy reaction! Simple alkenes lead to aldehydes and more complex lead to ketones. Synthesis Summary: In short: REDUCTION From Acid Chloride to Aldehyde – Bu3SnH (as a source of H-) From Acid Chloride to Ketone – R2CuLi (as a source of R) OXIDATION From Alcohol to Aldehyde/Ketone – PCC From Alkene to Aldehyde/Ketone – O3 then PPh3 – Reactions with Carbon Nucleophiles and Hydride Donors As mentioned earlier, aldehydes and ketones do not react with weak hydride donors (eh Bu3SnH) or organocopper reagents (eg R2CuLi) – they need more powerful reagents. The Continue reading >>
Synthesis Of Α-cf3 Ketones From Alkenes And Electrophilic Trifluoromethylating Reagents By Visible-light Driven Photoredox Catalysis
Highlights • • Visible light photoredox trifluoromethylation of alkenes is performed. • An electrophilic trifluoromethylating reagent (Togni's reagent) was used. • Abstract α-Trifluoromethyl ketones are important fluorinated intermediates and products in chemical synthesis and medicinal development. Herein, visible light-catalyzed photoredox trifluoromethylation of 1-aryl-2-alkyl substituted alkenes using an electrophilic trifluoromethylating reagent to produce α-trifluoromethyl ketones is reported. Two possible pathways involving either a trifluoromethyl radical or a styrene radical cation are proposed and discussed. Graphical abstract Continue reading >>
Ozonolysis
In this video, we're going to look at the cleavage of alkenes using a reaction called ozonolysis. So over here on the left I have my generic alkene, and to that alkene we're going to add O3 in the first step, which is ozone. And in the second step, we're going to add DMS, which is dimethyl sulfide. And be careful because there are different regions you could add in the second step, so make sure to learn the one that your professor wants you to use. If you use it DMS, you're going to get to a mixture of aldehydes and or ketones for your product, depending on what is attached to your initial alkene. So let's start by looking at a dot structure for ozone. So over here on the left is a possible structure for ozone. And we can draw a resonant structure by taking these electrons and moving them in here to form a double bond between those two oxygens. And now it pushed these electrons in here off onto the oxygen on the left. So let's go ahead and draw the other resonant structure. So now I would have a double bond between my two oxygens on the right. The oxygen on the far right has two lone pairs of electrons around it now. The oxygen in the center still has a lone pair of electrons on it, and the oxygen on the far left now has three lone pairs of electrons on it. So the oxygen on the far left now has a negative 1 formal charge, and the oxygen on the top here still has a plus 1 formal charge. And so those are our two resonant structures. Remember that the actual molecule is a hybrid of these two resonant structures. So let's go ahead and pick one of those resonant structures. I'm just going to take the one on the right. So let me just go ahead and redraw the resonant structure on the right. And so we're going to do the one that has the negative charge on the oxygen on the far Continue reading >>
Synthesis Of Aldehydes & Ketones
Aldehydes and ketones can be prepared using a wide variety of reactions. Although these reactions are discussed in greater detail in other sections, they are listed here as a summary and to help with planning multistep synthetic pathways. Please use the appropriate links to see more details about the reactions. Continue reading >>
