Chem 232 Chapter 16

Pyridoxine

Vitamin B6, closely related to Pyridoxal phosphate (PLP)

Carboxylic acid treated with LiAlH4

carboxylic acid is reduced all they way to the primary alcohol because reagent is a very powerful reducing agent, aldehyde not formed

Acids and bases

catalyze the formation of hemiacetals

strong hydrogen bongs between their molecules

cause aldehydes and ketones to have lower boiling points than corresponding alcohols

(polar) carbonyl group

causes aldehydes and ketones to have higher boiling points that hydrocarbons of the same molecular weight

Enamine

consists of an amine function bonded to the sp2 carbon of an alkene.

Thioacetal formation with subsequent "desulfurization" with hydrogen and Raney nickel gives

conversion of carbonyl groups of aldehydes and ketones to ─CH2─ groups

Carboxylic acid treated with SOCl2

converted to acyl chloride

a,B-unsaturated acid formation

cyanohydrin + 95% H2SO4

a-Hydroxy acid formation

cyanohydrin + HCl/H20/heat

b-aminoalcohol formation

cyanohydrin + LiAlH4/H20

diisobutylaluminum hybride, (DIBAL-H)

derivative of aluminum hydride less reactive than LAH

lithium tri-tert-butoxy-aluminum hybride

derivative of aluminum hydride less reactive than LAH

What causes the addition reaction to be more favourable in ketones

electron-withdrawing substituents (e.g., ─CF3 or ─CCl3 groups) cause the carbonyl carbon to be more positive (and the starting compound to become less stable)

transamination

enzymatic reaction with PLP which converts amino acids to ketones for use in the citric acid cycle

Aldehydes and ketones reacted with secondary amines

form enamines

Aldehydes and ketones reacted with alcohols

form hemiacetals and acetals by equilibrium reaction

Aldehydes and ketones reacted with primary amines

form imines

Cyanohydrin undergoes acidic hydrolysis

forms a-hydroxyacids or a,B-unsaturated acids

Wolff-Kishner Reduction

Reduces ketone to a methylene group by heating the ketone with hydrazine and a base. NaNH2 and KOH.

Acid-catalyzed acetal formation

(from hemiacetal) -protonation of the hydroxyl group leads to elimination of water and formation of a highly reactive oxonium cation -attack on the carbon of the oxonium ion by a second molecule of the alcohol followed by removal of a proton

base-catalyzed hemiacetal formation

-An alkoxide anion acting as a nucleophile attacks the carbonyl carbon atom, an electron pair shifts onto the oxygen atom producing a new alkoxide anion -The alkoxide anion abstracts a proton from an alcohol molecule to produce the hemiacetal and regenerates an alkoxide anion

Wittig reaction mechanism

-The first reaction is a nucleophilic substitution reaction, the aldehyde or ketone combines with the ylide in a cycloaddition reaction to form the four-membered ring of an oxaphosphetane -The second reaction is an acid—base reaction, the oxaphosphetane decomposes to form the alkene and triphenylphosphine oxide. The driving force for the reaction is the formation of the very strong phosphorus-oxygen bond in triphenylphosphine oxide.

Baeyer-Villiger Oxidation Mechanism

-The peroxycarboxylic acid attacks the carbonyl group of the protonated ketone or aldehyde, leading to a tertrahedral intermeditate -a group bonded to the initial ketone or aldehyde carbon migrates to oxygen, producting the ester (or lactone) as the peroxycarboxylic acid is released as carboxylic acid.

Best conditions for cyanohydrin formation

-cyanide anion present to act as nucleophile, use of potassium cyanide, or any base that can generate cyanide anions from HCN, increases the reaction rate as compared to the use of HCN alone

Mechanism for the Wolff-Kishner Reduction

-hydrazine hydrate reacts with the carbonyl compound to form a hdrazone -base promoted tautomerizating transfers a proton from nitrogen to carbon -elimination of N2 leads to carbanion which is then protonated

acid-catalyzed hemiacetal formation

-protonation of the aldehyde or ketone oxygen makes the carbonyl carbon more susceptible to nucleophilic attack, -an alchol molecule adds to the carbon of the oxonium cation, -the transfer of a proton from the positive oxygen to another molecule of the alcohol leads to the formation of the product

Hydrate formation

-water attacks the aldehyde carbonyl carbon atom -a proton is lost from the positive oxygen atom and a proton is gained at the negative oxygen atom

Enamine formation mechanism

1. the amine adds to the ketone or aldehyde carbonyl to form a tetra hedral adduct. Intermolecular proton transfer leads to the aminoalcohol intermediate 2. The aminoalcohol intermediate is protonated by the catalystic acid. Contribution of an unshared electron pair from the nitrogen atom and departure of a water molecule leads to an iminium cation intermediate 3. A proton is removed from the carbon adjacent to iminium group. Proton removal occurs from the carbon because there is no proton to remove from the nitrogen of the iminium cation. This step form the product, neturalizes the formal charge and regenerates the cataylic acid

Reasons Aldehydes and ketones are especially susceptible to nucleophilic addition

1. the nucleophile can attack from above or below 2. the positive charge on the carbonyl oxygen atom means it is especially susceptible to attack by nucleophile 3. the negative charge on the carbonyl oxygen means that nucleophilic addition is susceptible to acid catalysis

Hemiacetal formation

1st step, alcohol attacks the carbonyl carbon, 2nd step, a proton is removed a from the positive oxygen and a proton is ganied at the negative oxygen

Cyanohydrin

A functional group consisting of a carbon atom bonded to a cyano group and to a hydroxyl group, i.e., RHC(OH)(CN) or R2C(OH)(CN), derived by adding HCN to an aldehyde or ketone.

hemiacetal

A functional group, consisting of an sp3 carbon atom bearing both an alkoxyl group and a hydroxyl group [i.e., RCH(OH)(OR′) or R2C(OH)(OR′)]. Results by nucelophilic addition of an alcohol oxygen to the carbonyl carbon of an aldehyde or a ketone

Imine

A structure with a carbon-nitrogen double bond. If the groups bonded to carbon are not the same, (E) and (Z) isomers are possible.

Hydrazone formation

Aldehyde or ketone + hydrazine

Thioacetal formation

Aldehyde or ketone reacted with thiol

Thioacetal

Aldehyde or ketone reacted with thiol, sulfur analogues of acetals. React with hydrogen and Raney nickel to yield hydrocarbons.

Carbaldehyde

Aldehydes in which the -CHO group is attached to a ring system

Ozonolysis

Alkenes cleaves, products are aldehydes and ketones

ylide

An electrically neutral molecule that has a negative carbon with an unshared electron pair adjacent to a positive heteroatom.

Oximes

An imine in which a hydroxyl group is bonded to the nitrogen atom. Derivatives of aldehydes and ketones, sometimes used to identify unknown aldehdes and ketones via melting points

Hydrazones

An imine in which an amino group (─NH2, ─NHR, ─NR2) is bonded to the nitrogen atom. Derivatives of aldehydes and ketones, sometimes used to identify unknown aldehdes and ketones via melting points

oxonium cation

Any compound containing a positively charged oxygen atom that forms three covalent bonds. Result of first step of nucleophilic addition when an acid catalyst is present and the nucleophile is weak.

Reason it is impossible to isolate most gem-diols from aqueous solutions

Evaporation of the water, for example, simply displaces the overall equilibrium to the right and the gem-diol (or hydrate) reverts to the carbonyl compound

Migratory aptitude of groups in Baeyer-Villiger Oxidation

H>phenyl>3 alkyl>2 alkyl>1 alkyl> methyl

Aldehyde treated with KMno4, HO- or Ah2), HO- then acid

OH replaces H group, aldehyde oxidization

Factors that favour aldhehyde reactivity in nucelophilic additions

Steric and Electronic

Tollen's Test (Silver Mirror Test)

The ease with which aldehydes undergo oxidation differentiates them from most ketones. Mixing aqueous silver nitrate with aqueous ammonia produces a solution known as Tollens' reagent. The reagent contains the diaminosilver(I) ion, Ag(NH3)2+. Although this ion is a very weak oxidizing agent, it oxidizes aldehydes to carboxylate anions. As it does this, silver is reduced from the +1 oxidation state [of Ag(NH3)2+] to metallic silver. If the rate of reaction is slow and the walls of the vessel are clean, metallic silver deposits on the walls of the test tube as a mirror; if not, it deposits as a gray-to-black precipitate. Tollens' reagent gives a negative result with all ketones except a-hydroxy ketones:

Horner-Wadsworth-Emmons reaction

a modification of the wittig reaction, involves the use of a phosphonate ester instead of a triphenylphosphonium salt, major product is the E-alkene isomer

Cyclic acetal

acetal favoured when ketone or aldehyde treated with an exccess of a 1,2-diol and a trace if acid

Hemiacetal treated with 2nd molar equivalent of alcohol

acetal formed

gem-diol

aldehyde hydrate, result of disolving aldehyde in water

2,4-dinitrophenylhydrazone formation

aldehyde or ketone + 2,4-dinitrophenylhydrazine

Oxime formation

aldehyde or ketone + hydroxylamine

phenylhydrazone formation

aldehyde or ketone + phenylhydrazine

Imine formation

aldehyde or ketone reacted with primary amine, takes place fastest between 4 and 5 pH, acid catalyzed, can form as a mixture of E and Z isomers 1. amine adds to the carbonyl group to form a dipolar tetrahedral intermediat 2. Proton transfer from nitrogen to oxygen produces an aminoalcohol 3. Protonation of the oxygen produces a good leaving group, loss of a molecule of water yields ion 4. transfer of a proton to water produces product and regenerates the catalytic hydronium ion

Electronic factors that favour aldhehyde reactivity in nucelophilic additions

alkyl groups are electron releasing, only one electron releasing group to patrially neutralize and thereby stabilize, the + charge at their carbon actom

Wittig reaction

allows the preparation of an alkene by the reaction of an aldehyde or ketone with the ylide generated from a phosphonium salt.

Swern oxidation

can prepare aldehydes from primary alcohols

PCC oxidation

can prepare aldehydes from primary alcohols with PCC and Ch2Cl2

acetal

has two ─OR groups attached to the same carbon atom

Aldehydes

have a carbonyl group bonded to a carbon atom on one side and a hydrogen atom on the other side

Ketones

have a carbonyl group bonded to carbon atoms on both sides

Cyclic hemiacetals

hemiacetal stable enough to be isolated

acetal formation

involves acid catalyzed formation of hemicetal then an acid-catalyzed elimination of water, followed by a second addition of the alcohol and loss of a proton. All reversible.

Friedal-Crafts Acylation

ketone created from arene

Common regaent used to carry our the Baeyer-Villiger oxidation

meta-chloroperoybenzoic acid (mCPBA)

In general, aldehydes are _____ reactive in nucelophilic additions than ketones

more

Acetal hydrolysis

place acetal in water and add acid catalyst acetal becomes aldehyde

Nucleophilic addition when an acid catalyst is present and the nucleophile is weak

reaction of the carbonyl oxygen with the acid enhances electrophilicity of the carbonyl group, in the first step the acid donates a proton to an electron pair of the carbonyl oxygen atom. The resulting protonated carbonyl compound, an oxonium cation, is highly reactive toward nucleophilic attack at the carbonyl carbon atom. The oxonium cation accepts the electron pair of the nucleophile then a base removes a proton from the postitively charged atom, regenerating the acid

Acyl chloride treated with lithium tri-tert-butoxy-aluminum hybride at −78 °C

reduced to aldehyde

Cyclic acetal treated with acid

reversal from cyclic acetal to aldehyde or ketone

Some bases that are typically used to form the ester carbanion in the HWE reaction

sodium hydride, potassium tert-butoxide, and butyllithium

Raney nickel

special nickel catalyst that contains adsorbed hydrogen

Acetal in basic solution

stable, acetal used as protecting group

Thiol

sulfur analogue of alcohols, reacts with aldehyde or ketone to form thioacetal

Chloral hydrate

textbook example of compound with strong electron withdrawing groups attached to the carbonyl group that can form stable gem-diols

Steric factors that disfavor ketone reactivity in nucelophilic additions

the two alkyl substituents at the carbonyl carbon cause greater steric crowding in the tetrahedral product and make it less stable. Therefore, a smaller concentration of the product is present at equilibrium.

Aldehyde or ketone reacted with thiol

thioacetal formed

Nucleophilic addition when the reagent is a strong nucleophile

trigonal planar aledehyde or ketone converted to tetrahedral product, nucleophile added to carbonyl carbon, hydrogen added to carbonyl oxygen

Electronic factors that disfavor ketone reactivity in nucelophilic additions

two electron-releasing groups and are stabilized more. Greater stabilization of the reactant relative to its product means that the equilibrium constant for the formation of the tetrahedral product from this reactant is smaller and the reaction is less favorable

Baeyer-Villiger oxidation

useful method for conversion of aldehydes or ketones to esters by the insertion of an oxygen from a peroxycarboxyilic acid (RCO3H). Widely used for synthesizing lactones from cyclic ketones.

Pyridoxal phosphate (PLP)

very very versatile, closely related to Pyridoxine (vitamin b6) , member of aldehyde family, often contins the clostely related functional group with a carbon-nitrogen double bond, the imine group.

Steric factors that favour aldhehyde reactivity in nucelophilic additions

when one group is hydrogen atom the central carbon of the tetrahedral product is less crowded and the product is more stable

Nitrile treated with Grignard reagent or an organolithium reagent followed by hydrolysis

yields a ketone