diabetestalk.net

Pka Of Ketone

Enolates, Enols, And Enamines

Enolates, Enols, And Enamines

Sort Define enolate, enol, and enamine. Give an example of each derived from acetone. 1.) Enolate: A molecule containing the C=C-O- functional group, or its resonance contributor -C-C=O. An enolate is the conjugate base of an enol. 2.) Enol: A molecule which has a hydroxyl group (OH) group directly bonded to an alkene (C=C). The name is a contraction derived from alkene alcohol. 3.) Enamine: A molecule containing the N-C=C functional group. The name is a contraction of alkene amine. Briefly explain why acetone (pKa 19) is more acidic than propane (pKa ~50). Recall: how do Ka and pKa work? (What does a large/small pKa indicate in terms of acidity?) - The conjugate base of acetone (the enolate) has significant resonance stabilization. - Whereas the conjugate base of propane (propyl carbanion) has NO resonance stabilization. - Bases that are more stable (weaker bases) are derived from stronger conjugate acids. Ka = [products]/[reactants] pKa = -logKa - Large pKa = weak acid - Small pKa = strong acid First draw (or look at pg. 244 thinkbook, Part 1 CFQ #4) and then rank the following compounds in order of pKa and briefly explain your logic: - Acetone - 2,4-Pentanedione - Methyl acetoacetate - Methyl acetate Considering the stability of conjugate bases helps us rank pKa values. - Everything else being equal, an enolate with a greater number of significant resonance contributors is more stable than an enolate with a lesser number of significant resonance contributors. - The enolates of 2,4-pentanedione and methyl acetoacetate each have three resonance contributors. One of these contributors is a minor, destabilizing contributor because the methoxy group can donate electron density to the adjacent carbonyl group by resonance. - This decreases the carbonyl's ability to accept e Continue reading >>

Ketone Bodies

Ketone Bodies

The use of ketone bodies as fuel by most tissues during a fast reduces the need for gluconeogenesis from amino acid carbon skeletons, slowing the loss of essential protein. During a fast, the liver is flooded with liberated FAs from adipose tissue. Liver mitochondria have the capacity to convert excess acetyl CoA, derived from fatty acid oxidation, into ketone bodies when the amount of Acetyl CoA exceeds oxidative capacity. These include acetoacetate, 3-hydroxybutyrate, and acetone. As ketone bodies are soluble, they can be transported in the blood to peripheral tissues where they can be reconverted into Acetyl CoA and oxidized in the TCA cycle. Production of Ketone Bodies During a fast, the liver is flooded with liberated FAs from adipose tissue. This inhibits pyruvate dehydrogenase in the TCA cycle and activates pyruvate carboxylase, shunting pyruvate towards OAA for transport out of the mitochondria and into gluconeogenesis. This leaves Acetyl CoA available for ketone body synthesis. Use of Ketone Bodies Ketone bodies are reconverted into acetyl CoA in the periphery, including brain, heart and muscle, although the liver cannot use them as fuel. Excessive Production of Ketone Bodies Excessive ketone production results in ketonemia and ketonuria, often observed in Type I diabetes. This results from high levels of fatty acid degradation and concomitant acetyl CoA synthesis. In diebetic individuals, urinary excretion can be as high as 5000 mg/d, and blood levels can go from 3 mg/dl (normal) to 90 mg/dl. Elevated ketone levels causes acidemia, as the pKa of the carboxyl group is 4. Excretion of glucose and ketone bodies also causes dehydration, and as a result, profound acidosis can occur. Ketoacidosis can also be the result of profound fasting. This information is for tr Continue reading >>

7.9: How Delocalized Electrons Affect Pka Values

7.9: How Delocalized Electrons Affect Pka Values

Resonance effects involving aromatic structures can have a dramatic influence on acidity and basicity. Notice, for example, the difference in acidity between phenol and cyclohexanol. Looking at the conjugate base of phenol, we see that the negative charge can be delocalized by resonance to three different carbons on the aromatic ring. Although these are all minor resonance contributors (negative charge is placed on a carbon rather than the more electronegative oxygen), they nonetheless have a significant effect on the acidity of the phenolic proton. Essentially, the benzene ring is acting as an electron-withdrawing group by resonance. As we begin to study in detail the mechanisms of biological organic reactions, we’ll see that the phenol side chain of the amino acid tyrosine (see table 5 at the back of the book), with its relatively acidic pKaof 9-10, often acts as a catalytic proton donor/acceptor in enzyme active sites. Exercise 7.4.1 Draw the conjugate base of 2-napthol (the major resonance contributor), and on your drawing indicate with arrows all of the atoms to which the negative charge can be delocalized by resonance. The base-stabilizing effect of an aromatic ring can be accentuated by the presence of an additional electron-withdrawing substituent, such as a carbonyl. For the conjugate base of the phenol derivative below, an additional resonance contributor can be drawn in which the negative formal charge is placed on the carbonyl oxygen. Now the negative charge on the conjugate base can be spread out over two oxygens (in addition to three aromatic carbons). The phenol acid therefore has a pKa similar to that of a carboxylic acid, where the negative charge on the conjugate base is also delocalized to two oxygen atoms. The ketone group is acting as an electron Continue reading >>

Chemistry Of Enolates And Enols – Acidity Of Alpha-hydrogens

Chemistry Of Enolates And Enols – Acidity Of Alpha-hydrogens

In the presence of carbonyl functional group, the alpha-hydrogens of a molecule exhibit acidity i.e. in the presence of a base they can be abstracted very easily to yield a carbanion. The acidity of the α-hydrogen of carbonyl compounds depends on the stability of the carbanion formed (which is the conjugate base in this case). If the carbanion is more stable, the alpha-hydrogen is more acidic. The carbanion can be stabilized either with resonance – i.e. the carbanion lone pair to the oxygen of the carbonyl to form the stabilized enolate, or by inductive effect – if electron withdrawing groups are directly attached to the alpha-carbon. Stabilization by inductive effect - if electron withdrawing groups are directly attached to the alpha-carbon. Note – Acidities of the alpha-hydrogen is measured in pKa. Lower pKa value of the hydrogen, more acidic it is. Comparison of Acidities of Alpha – Hydrogens Note – The pKa values are given assuming the R’ and R” groups are alkyl (mostly methyl group) and are an approximate value. 1] α-Hydrogens of Ketones vs Aldehydes The alpha-hydrogens of ketones (pKa = 20) are less acidic as compared to aldehydes (pKa = 17). This is because the alkyl group R” of ketones pushes electrons via inductive effect on to the alpha-carbon. This would increase the electron density at the alpha-carbon to slightly destabilize the formation of the conjugate base – carbanion. 2] α-Hydrogens of Ketones vs Esters The alpha-hydrogen of ketones (pKa = 20) is more acidic as compared to the alpha-hydrogens of esters (pKa = 25). The reason for this is that the ester functional group has free lone pairs on the oxygen which can participate in resonance with carbonyl group. This resonance competes with the resonance of the stabilization of the enola Continue reading >>

Chapter 18 Lecture 1 Enols

Chapter 18 Lecture 1 Enols

Chapter 18 Lecture 1 Enols Enolate Ions Carbonyl Reactivity Nucleophilic carbonyl oxygen Electrophilic carbonyl carbon a-carbon containing acidic a-protons (the subject of this chapter) Acidity of Aldehydes and Ketones pKa of protons alpha to an aldehyde or ketone carbonyl = 19-21 Ethene pKa = 44 Ethyne pKa = 25 Alcohol pKa = 15-18 Strong bases can remove a-hydrogens to produce an Enolate Ion Enolate Ion Why are carbonyl a-protons acidic? The conjugate base is stabilized by the enolate ion resonance structures The d+ carbon of the carbonyl destabilizes the a C—H bond C. Formation of Enolate Ions LDA (lithium diisopropyl amide) or other strong bases are used Aprotic solvents are used to prevent solvent deprotonation Enolate Resonance Hybrid The a-carbon and the oxygen of an enolate ion are both nucleophilic Ambident = “two-fanged†= a species that can react at 2 different sites to give 2 different products The carbon atom is the normal site of reaction by SN2. This type of reaction is called alkylation or C1-alkylation of the enolate ion. The oxygen atom is the normal site of protonation, forming an enol, which will tautomerize to the original ketone. II. Keto-Enol Equilibria Ketone—Enol Tautomerization This reaction is reversible, and the extent of reaction depends on conditions Base-catalyzed Enol-Keto Equilibration Base removes proton from the enol The mechanism is the reverse of the original enolate formation Acid Catalyzed Enol-Keto Equilibration Protonation occurs at the double bond Resonance stabilized C is next to O Protonated carbonyl deprotonates to give the keto form Both reaction are fast if the catalyst (B- or H+) are present Keto form is usually dominant Keto to enol tautomerization mechanisms are the reverse of those above Effects o Continue reading >>

Aldehyde

Aldehyde

An aldehyde Formaldehyde, the simplest of the aldehydes An aldehyde /ˈældɪhaɪd/ or alkanal is an organic compound containing a functional group with the structure −CHO, consisting of a carbonyl center (a carbon double-bonded to oxygen) with the carbon atom also bonded to hydrogen and to an R group,[1] which is any generic alkyl or side chain. The group—without R—is the aldehyde group, also known as the formyl group. Aldehydes are common in organic chemistry. Many fragrances are aldehydes. Structure and bonding[edit] Aldehydes feature an sp2-hybridized, planar carbon center that is connected by a double bond to oxygen and a single bond to hydrogen. The C–H bond is not ordinarily acidic. Because of resonance stabilization of the conjugate base, an α-hydrogen in an aldehyde (not shown in the picture above) is far more acidic, with a pKa near 17, compared to the acidity of a typical alkane (pKa about 50).[2] This acidification is attributed to (i) the electron-withdrawing quality of the formyl center and (ii) the fact that the conjugate base, an enolate anion, delocalizes its negative charge. Related to (i), the aldehyde group is somewhat polar. Aldehydes (except those without an alpha carbon, or without protons on the alpha carbon, such as formaldehyde and benzaldehyde) can exist in either the keto or the enol tautomer. Keto-enol tautomerism is catalyzed by either acid or base. Usually the enol is the minority tautomer, but it is more reactive. Nomenclature[edit] IUPAC names for aldehydes[edit] The common names for aldehydes do not strictly follow official guidelines, such as those recommended by IUPAC, but these rules are useful. IUPAC prescribes the following nomenclature for aldehydes:[3][4][5] Acyclic aliphatic aldehydes are named as derivatives of the lon Continue reading >>

The Pka Table Is Your Friend

The Pka Table Is Your Friend

The importance of pKas in organic chemistry can’t be overestimated, in my opinion. Not knowing pKa’s in organic chemistry is like not knowing the value of the hands in poker. In this scheme, alkyl anions are the equivalent of the royal flush – they win the proton from everything underneath them in the table. Why are pKas so important? Because every nucleophile is potentially a base, and vice versa. If you have a reaction where it looks like you might get SN2 or E2, look closely first – is there any chance of a simple acid-base reaction? For instance, take NaOH plus an alkyl thiol, R–SH. Is it an SN2? Or possibly an E2? Both are incorrect. The reaction that happens is the simplest one – deprotonation of SH, to provide water and the deprotonated thiol. Also, the pKa table tells you about leaving group ability. Good leaving groups are weak bases! If you don’t know the relative values of the pKas of the major functional groups, you’ll be flying blind in the course. Expect to hit a tree. PDF VERSION NOW AVAILABLE (click here) For more complete lists, be sure to check out Evans, Reich, and Stoltz. (check out the resources on Reich’s page by the way – fantastic!) Blessed are the OCD, for they produce the most beautiful and complete web resources. Organic Chemistry 2 builds on the concepts from Org 1 and introduces a lot of new reactions. Here is an index of posts for relevant topics in Organic Chemistry 2: [Hint – searching for something specific? Try CNTRL-F] General Posts About Organic Chemistry 2 Oxidation And Reduction Alcohols, Ethers, And Epoxides Conjugation, Dienes and Pericyclic Reactions Aromaticity and Aromatic Reactions Aldehydes and Ketones Carboxylic Acid Derivatives General Posts Concerning Organic Chemistry 2 Oxidation And Reduction Alcoho Continue reading >>

· Compounds With Lower Pka Values Are Relatively Stronger Acids.

· Compounds With Lower Pka Values Are Relatively Stronger Acids.

Acid/Base and pKa values Major concepts · A quantitative scale of the strength of an acid in protonating water gives us pKa values · Because all pKa values are relative to water, they can be used to determine the relative strength of acids to each other · Weaker acids are relatively more stable, less reactive, acids. Stronger acids are relatively less stable, more reactive, acids. · Stronger acids have weaker conjugate bases; weaker acids have stronger conjugate bases. This can be restated that “Less stable acids have more stable conjugate bases,†or “More reactive acids have less reactive conjugate bases.†· The equilibrium of a reaction lies toward the weaker acid/base pair because they are more stable. Vocabulary · pKa values · stronger/weaker; less stable/more stable; more reactive/less reactive Students should be able to: · Know the pKa values of the protons of typical functional groups from memory · Compare the relative acidity of two compounds using pKa values · Use both pKa values and base stability principles to determine direction of equilibrium · Given reagents, predict whether or not an acid/base reaction will happen and what the products will be. On the following page are a list of pKa values for functional groups and protonated functional groups. Eventually, you will need to know these! pKa chart of the functional groups: values to know 1. Protonated carbonyl pKa = -2 to -3 2. Protonated alcohol or ether pKa = -2 to -3 3. Carboxylic acid pKa = 4-5 4. Ammonium ion pKa = 9-10 5. Phenol pKa = 10 6. Thiol pKa = 10 7. Alcohol pKa = 16-18 8. Water pKa = 15.7 9. Amide pKa = 18 10. Alpha proton of ketone/aldehyde pKa = 20 11. Alpha proton of ester pKa = 25 12. Terminal alkyne pKa = 25 13. Amine pKa = 38-40 14. A Continue reading >>

Chapter 17 Notes - Carbonyl Compounds

Chapter 17 Notes - Carbonyl Compounds

Carbonyl Functional Groups usually subdivided into two families: aldehydes and ketones both R groups are C or H carboxyl derivatives X is some electronegative element (halogen, O, N, S, others) The Carbonyl Group - Structure and Properties polar C=O double bond O is nucleophilic reacts with acids & electrophiles C is electrophilic reacts with Lewis bases and nucleophiles alpha-C-H position is acidic (pKa ~ 20) Aldehyde Nomenclature IUPAC: alkanal -al suffix, with carbonyl assumed #1 in parent chain -carbaldehyde suffix (if aldehyde can't be part of the parent) e.g., cyclohexanecarbaldehyde common nomenclature: formaldehyde acetaldehyde propionaldehyde butyraldehyde benzaldehyde Ketone Nomenclature IUPAC: alkanone -one suffix, with number -oxo- prefix if necessary e.g., 4-oxopentanal common nomenclature: dialkyl ketone acetone acetophenone benzophenone acyl- as prefix e.g., acetyl or benzoyl, as in acetylcyclopropane Precedence Order of Functional Groups decides which gets to be the parent compound (suffix) lower functional groups must be named as substituents (prefixes) carboxylic acid aldehyde ketone alcohol amine thiol Characteristic Properties polar H-bond acceptors, but not H-bond donors Mass spec shows alpha cleavage (stable acylium ion RCO+) or McLafferty rearrangement (split between alpha and beta carbons) NMR shows aldehyde C-H at 9-10 ppm, C=O at 180-210 ppm IR shows strong C=O stretch at 1600-1800 cm-1 exact position depends on ring strain, conjugation UV shows weak n -> pi* at ~ 300 nm and pi -> pi* at ~ 200 nm exact position and strength of the absorption depends on conjugation Nucleophilic Addition to Carbonyls the major reaction of carbonyl compounds General Trends: aldehydes more reactive than ketones (due to steric hindrance with ketones) aromatic carbon Continue reading >>

R = Alkyl Or Aryl (c)

R = Alkyl Or Aryl (c)

17.2 How Aldehydes and Ketones React (Part I) 1 d+ Y = alkyl, aryl or H (class II) (No leaving group) d- Electron rich (Lewis base, Nu) Electron deficient (Lewis acid, E+) Main Menu Class I vs. Class II Carbonyl Compounds 2 Class II Y = NR’2 (amide) = OR’ (ester, carboxylic acid) = OCOR’ (acid anhydride) = X (acyl halide) Class I Y = H (aldehyde) = R’’ (ketone) H-H (pKa = 35) R-H (pKa = 50) Hydride (H-) and carboanion are not leaving groups Relative Reactivity of Class I and Class II Carbonyl Compounds 3 acyl halide >> > > > > acid anhydride ketone aldehyde ester amide Esters and amides are more stable than ketones and aldehydes due to their resonance stabilization. H R’ Nucleophilic Addition (Class II) 4 1. General mechanism in basic condition: 2. General mechanism in acidic condition: Important pKa to Remember 5 Names Acids H-Z Approx. pKa Conjugate Base, :Z General Roles of :Z Alkane (2°) 51 Base as Li+ salt Nucleophile as Grignard reagent Amine 38 Base and Nucleophile Hydrogen 35 Base in NaH, CaH2 Nucleophile in LiAlH4, NaBH4 Alcohol water 15-16 Often as a base but can be a nucleophile Ammonium 10-11 Weak base, but can be a nucleophile Thiol 10-11 Nucleophile Carboxylic Acid 4-5 Weak base, poor leaving group Hydrochloric Acid -7 Leaving group, poor nucleophile Types of Nucleophile for Class II Carbonyl Groups 6 1. Carbon as the nucleophilic atom pKa = 50 Basic condition 2. Hydrogen as the nucleophilic atom carboanion hydride Mostly basic condition 3. Nitrogen as the nucleophilic atom 1° and 2° amines Mostly acidic condition 4. Oxygen as the nucleophilic atom Acidic condition 1° alcohols Carbon as the Nucleophilic Atom: Grignard Reagents 7 Carboanions are highly reactive. pKa = 50 Hard to find a base to do the dep Continue reading >>

Enolate Formation From Ketones

Enolate Formation From Ketones

Voiceover: In order to see how to form enolate anions, and in this video we're just gonna look in more detail how to form enolate anions from ketones. And so the ketone we have here is acetone. To find our alpha carbon, we just look at the carbon next to our carbonyl carbon, so this could be an alpha carbon, and this could be an alpha carbon. Each one of those alpha carbons has three alpha protons, and so there's a total of six. I'm just gonna draw one in here, and this is the one that we're going to show being deprotonated here. So, the base that's going to deprotonate acetone, we're gonna use LDA, which is Lithium Diisopropyl Amide And, I could go ahead and draw in the Lithium here, so Li Plus, and then we see the two isopropyl groups like that, a negative one charge on our nitrogen. So this is a very strong base, it's also very bulky and sterically hindered. So you can think about a lone pair of electrons in the nitrogen, taking that proton, leaving these electrons behind on this carbon, so we can go ahead and draw the conjugate base here. We would have electrons on this carbon now, that's a carbanion, so let me go ahead and show those electrons, these electrons in here magenta, are gonna come off onto this carbon. And this carbon is a [carbanae] because remember there's also two other hydrogens attached to it. So that's what gives it a negative one formal charge here. We can draw our resonance structure, we can show these electrons in magenta moving in here, these electrons coming off onto our oxygen, so for our resonance structure we would show the negative charge is now on our oxygen, this would be a negative one formal charge like that now. So the electrons in magenta moved into here to form our double bond, and then we can show the electrons in here in the blue Continue reading >>

Acidity Of

Acidity Of

a-Hydrogens In the following table, the acidity of the H for various enolate systems and other closely related systems are given. You should be able to justify the trends in this data ! Why are the protons adjacent to carbonyl groups acidic ? As we have advocated before, look at the stabilisation of the conjugate base. Notice the proximity of the adjacent p system, and hence the possibility for RESONANCE stabilisation by delocalisation of the negative charge to the more electronegative oxygen atom. The more effective the resonance stabilisation of the negative charge, the more stable the conjugate base is and therefore the more acidic the parent system. Let's compare pKa of the common systems: aldehyde pKa = 17, ketone pKa = 19 and an ester pKa = 25, and try to justify the trend. The difference between the 3 systems is in the nature of the group attached to the common carbonyl. The aldehyde has a hydrogen, the ketone an alkyl- group and the ester an alkoxy- group. H atoms are regarded as having no electronic effect : they don't withdraw or donate electrons. Alkyl groups are weakly electron donating, they tend to destabilise anions (you should recall that they stabilise carbocations). This is because they will be "pushing" electrons towards a negative system which is unfavourable electrostatically. Hence, the anion of a ketone, where there are extra alkyl groups is less stable than that of an aldehyde, and so, a ketone is less acidic. In the ester, there is also a resonance donation from the alkoxy group towards the carbonyl that competes with the stabilisation of the enolate charge. This makes the ester enolate less stable than those of aldehydes and ketones so esters are even less acidic. The most important reactions of ester enolates are the Claisen and Dieckmann cond Continue reading >>

9/5/10

9/5/10

Ketoacidosis PY GENERAL - ketoacidosis is a high anion gap metabolic acidosis due to an excessive blood concentration of ketone bodies (keto-anions). - ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) are released into the blood from the liver when hepatic lipid metabolism has changed to a state of increased ketogenesis. - a relative or absolute insulin deficiency is present in all cases. CAUSES The three major types of ketosis are: (i) Starvation ketosis (ii) Alcoholic ketoacidosis (iii) Diabetic ketoacidosis Starvation Ketosis - when hepatic glycogen stores are exhausted (eg after 12-24 hours of total fasting), the liver produces ketones to provide an energy substrate for peripheral tissues. - ketoacidosis can appear after an overnight fast but it typically requires 3 to 14 days of starvation to reach maximal severity. - typical ketoanion levels are only 1 to 2 mmol/l and this will usually not alter the anion gap. - the acidosis even with quite prolonged fasting is only ever of mild to moderate severity with ketoanion levels up to a maximum of 3 to 5 mmol/l and plasma pH down to 7.3. - ketone bodies also stimulate some insulin release from the islets. - patients are usually not diabetic Alcoholic ketoacidosis Presentation - a chronic alcoholic who has a binge, then stops drinking and has little or no oral food intake for a few days (ethanol and fasting) - volume depletion is common and this can result in increased levels of counter regulatory hormones (eg glucagon) - levels of FFA can be high (eg up to 3.5mM) providing plenty of substrate for the altered hepatic lipid metabolism to produce plenty of ketoanions - GIT symptoms are common (eg nausea, vomiting, abdominal pain, haematemesis, melaena) - acidaemia may be severe (eg pH down to 7.0) - plasma glucose Continue reading >>

When A Compound Has A Low Pka It Is Able To

When A Compound Has A Low Pka It Is Able To

When a compound has a low pKa it is able to dissociate more easily than a compound The changes in pH caused the ethyl-4-amino benzoate to become polar or non-polar by The pKa of 9-fluoronone is 45 while the pKa of most ketone compounds are 20. Fluoronone has a greater pKa because there are double bonds bound by the carbon atoms so it The principles in this lab can be applied to everyday life such as how to determine how so there could be different reactions of medications due to the pH levels in specific organs. Continue reading >>

Equilibrium And Kinetic Acidities Of Benzylic Ketones. Application Of The Marcus Equation To The Deprotonation Of Carbon Acids

Equilibrium And Kinetic Acidities Of Benzylic Ketones. Application Of The Marcus Equation To The Deprotonation Of Carbon Acids

Note: In lieu of an abstract, this is the article's first page. This user does not have a subscription to this publication. Please contact your librarian to recommend that your institution subscribe to this publication. Purchase temporary access to this content. Use your free ACS Member Universal Access (if available) Continue reading >>

More in ketosis