OXO compounds - unideb.hu

Classification of oxo compounds, bonding system of oxogroup, the stability of the C = O bond. Physical properties. The acid-base properties of aldehydes and ketones, keto-

enol tautomerism. Nucleophilic addition reactions with O-, S-, N- and C-nucleophiles, the reversible nature of the

addition. Condensation reactions. Oxidation and reduction reactions. The reactions of -carbon; aldol dimerization, -halogenation. The nucleophilic addition reactions of

,b-unsaturated oxo compounds. Preparation of aldehydes and ketones.

OXO compounds

Classification of compounds with C=O bond

Functional group:

Classification1. according to functional group 3. according to the attached hydro carbonyl chain

- aldehydes (RCHO) - aliphatic or aromatic / heteroaromatic- ketones (RR1CO) - non-cyclic or cyclic

2. numbers of functional groups- monoaldehyde/ketone- dialdehyde/diketone- polyaldehyde/polyketone

non-cyclic ketonecyclic aldehyde cyclic ketone

Aldehydes and ketones contain an acyl group bonded either to hydrogen or to anothercarbon.

acyl group

Nomenclature1. Aldehydes

Only substitutive nomenclature, NO functional class nomenclature- al suffix, prefix: formyl if there is a group with higher priority. Note: there is no location

number because the formyl group (-CHO, NOT -COH !!!) can be only the end of the chain ≥ 3 formyl groups: main chain + polyaldehyde suffix with location numbersSimilar if the aldehyde is cyclic!

When a formyl group (-CHO) is attached to a ring, the ring name is followed by thesuffix -carbaldehyde.

Certain common names of familiar aldehydes are acceptable as IUPAC names. A fewexamples include

Nomenclature 2.

Semi-trivial nomenclature of aldehydes – the Latin name of the corresponding carboxylic acid + "aldehyde" ending

Eg: „acidumaceticum” → acetaldehyde

And common names…

Nomenclature 3.

More examples

2. KetonesBoth substitutive and the functional class nomenclature!Substitutive ~: -one suffix, prefix: oxo if there is a group with higher priority. If there are more oxo groups: location numbers and multiplier

With ketones, the -e ending of an alkane is replaced by -one in the longest continuous chain containing the carbonyl group. The chain is numbered in the direction that provides the lower number for this group.

Functional class ~: related hydrocarbons + ketone end

Although substitutive names of the type just described are preferred, the IUPAC rules also permit ketones to be named by functional class nomenclature. The groups attached to the carbonyl group are named as separate words followed by the word “ketone.” The groups are listed alphabetically.

Nomenclature 4.

Semi-trivial and common names

Nomenclature 5.

More examples

Fuctional groups

Bonding system of C=O bond

Heteronuclear + bond system with sp2

pillar atoms – similarity to alkenes

Difference to alkenes: different EN strongly polarised bond

Approx.: 40-50% ionic bondDipole molecules (μ = 2.1-2.5 D)

C=O double bond shorter and stronger bonds, planar trigonal arrangement (depending the size of the attached groups and nonbonding e-pairs

dC=O ~0.121 nm ↔ dC-O = 0.143 nm (EtOH, Me2O)

Comparing bond energies (E)

Bond E (kJ/mól)

Bond E (kJ/mol)

CH3-CH3 369 CH3-OH 321

CH2=CH2 592 CH2=O 687

A C=O bond is stronger then C=C double bond and stronger then

2xC-O single bond!!

Special thermodynamic stability

Cleavage of C=O bond is not favoured

reversible AdN reactions

Comparison of the stability of aldehydes and ketones

- electron donating groups (alkyl) → ketones are more stable than aldehydes

Electronic effect of carbonyl group → -I (inductive effect) and –M (mesomeric effect)

The pz orbital of the carbon is empty decreased e-density

(Important!! –M if only a neighbouring -system is exists!)

Physical properties if C=O compounds

1. Melting point, boiling point Mp (oC) Mp (oC)

HCHO -92 - -

MeCHO -122 - -

EtCHO -81 Me2CO -95

PrCHO -99 MeCOEt -87

BuCHO -92 MeCOPr

EtCOEt

-78

-40

Mp:Homologous series exists, but there is no characteristic path

Bp (oC) Bp (oC)

HCHO -21 - -

MeCHO 20 - -

EtCHO 50 Me2CO 56

PrCHO 76 MeCOEt 80

BuCHO 103 MeCOPr

EtCOEt

102

102

C5H12 BuCl Et2O PrCHO EtCOMe BuOH

Mw 72 78 74 72 72 74

Bp (oC) 36 47 35 76 80 118

Bp values of different analogues

Bp:dipole-dipole interactions are stronger compare to

R-Cl / R2O But weaker than H-bond interactions (alcohols) !!

2. Solubility in water – determining factors: the stability of H-bonds

S[g/mL] 8 4 37 0.07

Generally C5, C6 significant solubility in water and also in organic solventsTypically: dipolar aprotic solvents

Chemical properties of C=O compounds

H-bridge acceptor character!!

1. Acid-base properties1.1. Acidity: carbonyl group –I, –M effect -H is easily can be cleaved! The carbonyl group acts as a powerful electron-withdrawing substituent, increasing the acidity of protons on the adjacent carbons. (like an acid: C-H acidity)

Delocalized (stable)

electron system

Under basic condition the -C become nucleophilic

C-C bond formation (see latter)

This proton is far

more acidic than a

hydrogen in an

alkane.

1.2. Basicity of carbonyl compounds – reaction with Brönsted or Lewis acids

Similar reactivity toward Lewis acids, too! Due to the two mesomeric structures stability is considerable! acid

catalysed reactions are important (enol formation)

Aldehydes and ketones are in equilibrium with their enol isomers.

1.3. Keto-enol tautomerism

Enols are related to an aldehyde or a ketone by a proton-transfer equilibrium known asketo–enol tautomerism. (Tautomerism refers to an interconversion between two structures that differ by the placement of an atom or a group. The keto and enol forms areconstitutional isomers. Using older terminology they are referred to as tautomers of each other.

The rate of enolization is catalyzed by acids

With unsymmetrical ketones, enolization may occur in either of two directions:

The ketone is by far the most abundant species present at equilibrium. Both enols arealso present, but in very small concentrations.

It is important to recognize that an enol is a real substance, capable of independentexistence. An enol is not a resonance form of a carbonyl compound; the two areconstitutional isomers of each other.

A 1,3 arrangement of two carbonyl groups (compounds called b-diketones) leads to a situation in which the keto and enol forms are of comparable stability.

The two most important structural features that stabilize the enol of a b-dicarbonylcompound are (1) conjugation of its double bond with the remaining carbonyl group and (2)the presence of a strong intramolecular hydrogen bond between the enolic hydroxylgroup and the carbonyl oxygen.In b-diketones it is the methylene group flanked by the two carbonyls that isinvolved in enolization. The alternative enol does not have its carbon–carbon double bond conjugated with the carbonyl group, is not as stable, and is present in negligible amounts at equilibrium.

methylene group flanked by the two carbonyls

BASE-CATALYZED ENOLIZATION: ENOLATE ANIONS

The proton-transfer equilibrium that interconverts a carbonyl compound and its enol canbe catalyzed by bases as well as by acids.

The key intermediate in this process, the conjugate base of the carbonyl compound, is referred to as an enolateion, since it is the conjugate base of anenol. Protonation of this anion can occur either at the carbon or at oxygen. Protonation of the carbon simply returns the anion to the starting aldehyde or ketone. Protonation of oxygen produces the enol.

Acid or base catalysis, equilibrium. Keto form is favoured (thermodynamic reason) except there is chance for conjugation or

intramolecular H-bond

Oxo Enol contant (%)

Me2CO 2.5 x 10-4

Cyclohexanone 0.02

PhCH2COCH3 3

MeCOCH2COOEt 8

MeCOCH2COMe 76

conjugation

H-bond

Conclusion

electrophile sp2 C Nu attack

AdNC=O driving force: the O has large EN and it readily forms OƟ, and it can take on H+

BUT the reaction is still reverse!!! Thermodynamic factors – C=O large bond E, stability reversible addition, < 100% conversion2 x C-O < C=O!

Many factors affect the location of the equilibrium.● electronic factors: a C=O increasing e- deficiency (electrophilicity) is better

ketone < aldehyde < HCHO● steric factors – sp2 C more crowded/angle tension easier addition

2. Addition with different Nu2.1. O-nucleophiles2.1.1. Water addition (hydration) – strongly depends on the

substituents!geminal diol product oxo K

HCHO 2280

MeCHO 1.06

Me3CCHO 0.23

CF3CHO 3.9 x 104

Me2CO 1.4 x 10-3

(CF3)2CO 1.2 x 106

2.1.2. Alcohol addition – in 2 steps (hemiacetal / acetal) The hemiacetals are usually unstable, not isolable(carbohydrates are exceptional)

Acetals are stableit can be cleaved under acidicconditions good protecting groups !!!

hemiacetal acetal

2.2. S-nucleophiles: thiol addition

Analogy to R-OH addition, Mostly: used as C=O protecting groups2.3. N-nucleophiles –R-NH2

● acid catalysis● addition is followed by a water elimination condensation reaction

The driving force for water elimination: X(N) = C double bond has greater thermodynamic stability than the addition product!

thioacetal

The most important condensation products (so-called „oxo derivatives")

2.4. C-nucleophiles– carbanion-type: C-C bond formation, chain prolongation

Irreversible reactionReason: no chance for elimination

2.4.1. Cyanide anion addition → cyanohydrins

Important use:

Methyl methacrylate (MMA)Polymethyl methacrylate (MMA) : Plexiglas

PMMA (Plexiglas)

Methyl methacrylate

Polymethyl methacrylate

2-Me-propenoic acid

2.4.2. Grignard compounds → alcohol formation

Formally: :CƟ equivalent

2.4.3. Terminal alkynes: deprotonation results a carbanion→ alcohol formation

Z1, Z2 = EWG ( C-H acidity!)

2.4.4. Aldol dimerization: C-H acidity of aldehydes and ketones

Generally:

Deprotonation: concentrated basic solution (NaOH); -H!!!The double role of the aldehyde /ketone – nucleophile source AND electrophileWater elimination: by acid catalysed or spontaneous depending on the substituentsReactivity: RCHO > R1R2CO

„Crossed” aldol dimerization2 nucleophile +

2 electrophile 4 products!

If ArCHO, 3o CHO, ketone –

selectivity

Only one partner can be electrophile, similar reaction with 3o aldehydes, too A typical example: synthesis of chalconesStarting material for flavonoids, heterocycles

-carbanion source: acid anhydrideInstead of ArCHO 3o aldehyde also can be used

Carboxylate is required to generate the corresponding nucleophilic carbanion

Knoevenagel-Doebner synthesis

Darzens condensation

LG = Hlg

C-Nu: from the -C of malonic acid

Wittig reaction – you know this☺

A ylide is neutral dipolar moleculecontaining a formally negatively charged atom (usually a carbanion) directly attached to a heteroatomwith a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both atoms have full octets of electrons.

3. Oxidation and reduction transformationsStarting point: intermediate oxidation level both reaction takes place

3.1. Reduction3.1.1. Reduction to alcohols

3.1.1.1. Catalytic hydrogenation - H2/Pd or Pt, NiSimilarity to the reduction of alkenes! (check alkenes!)

Chemisorption on the surface of the catalyst -bonding and H-H bond loosening

Generally, cis-addition - explanation: "four-center" model

3.1.1.2. Reduction with metal hydrides NaBH4, LiAlH4 (LAH) and modified derivatives

Actually hydride ion (: H) as a specific nucleophile AdN reaction C=O then protonation

3.1.2. Reduction to alkanes (formation to methylene group)

3.1.2.1. Clemmensen reduction – reduction of ketones with Zn amalgam

Strongly basic medium, an aqueous or alcoholic solution

Extension: Huang-Minlon (1946)Solvent: ethylene glycol-based compounds (K

complexing, high boiling point).

3.1.2.2. Kishner-Wolff-reduction – reduction of hydrazones

3.2. Oxidation3.2.1. Oxidation of aldehydes - simple oxygen insertion, takes place easily, the process leading to a single producttypical reagents: KMnO4, H2CrO4 and other Cr(VI), Br2/H2O, …

Fehling’s test- complexed Cu (II) → Cu (I) redox processFehling’s A solution: CuSO4/H2OFehling’s B solution: K-Na-tartarate + NaOH /H2O

Fehling's solution is prepared by combining two separate solutions, known as Fehling's A and Fehling's B. Fehling's A is aqueous solution of copper(II) sulfate, which is deep blue. Fehling's B is a colorless solution of aqueous potassium sodium tartarate (also known as Rochelle salt) made in a strong alkali, commonly with sodium hydroxide. Typically, the L-tartrate salt is used. The copper(II) complex in Fehling's solution is an oxidizing agent and the active reagent in the test. The deep blue active ingredient in Fehling's solution is the bis(tartrate) complex of Cu2+. The tartrate tetraanions serve as bidentate alkoxide ligands.

Cu2O (red precipitate) is formed

Special oxidative reactions (test reactions)To distinguish aldehydes and ketones use the Fehling and Silver mirror tests

Silver mirror reaction (Tollens’ reaction)

Tollens’ reagent is a chemical reagent used to determine the presence of an aldehyde, aromatic aldehyde and alpha-hydroxy ketone functional groups. The reagent consists of a solution of silver nitrate and ammonia. It was named after its discoverer, the German chemist Bernhard Tollens. A positive test with Tollens' reagent is indicated by the precipitation of elemental silver, often producing a characteristic "silver mirror" on the inner surface of the reaction vessel. - complexed Ag (I) → Ag (0) redox process withaldehydes (metallic silver precipitation); Tollens reagent: AgNO3 + NH4OH → Ag[NH3]2;

2 [Ag(NH3)2]+ + RCHO + H2O → 2 Ag(s) + 4 NH3 + RCO2H + 2 H+

● Cannizzaro reaction –by disproportionation!

Parallel formation of carboxylic acid and 1o alcohol. Requirement: the R group does NOT contain any -hydrogen!! E.g. benzaldehyde

● Autooxidation of aromatic aldehydes – radical chain reaction(h, light), in the presence of oxygene (air) Storage: in brown bottle, in the presence of stabilizer materials

3.2.1. Oxidation of ketones – stronger conditions, a mixture of carboxylic acids

typical reagent : KMnO4/H

Synthetic significance is smaller!

4. Reactions of -carbon atom – enol intermediate! The presence of -hydrogen is a fundamental criterion.

4.1. -Halogenation

ox.

The Cannizzaro reaction, named after its discoverer Stanislao Cannizzaro, is a chemical reaction that involves the base-induced disproportionation of a non-enolizable aldehyde

Autoxidation is any oxidation that occurs in open air or in the presence of oxygen (and sometimes UV radiation).

formally substitution (~ halogenation of alkanes)BUT! ● not photocatalysis,● acid or base catalysis● substitution ONLY in -position● possible successive -halogenation (di- and trihalogenation) „haloform”-reaction

Electrophile: NO

Dominant tautomer: -oximinoketone (reason: conjugation)

5. Nucleophile addition reaction of ,b-unsaturated aldehydes and ketones

Check: mesomeric structures of ,b-unsaturated oxo compounds

Two electrophilic centres, two possible attacks!

4.2. -Nitrosation

Due to lower the stability of the enol

formally 3,4-adduct!

Full range of nucleophiles: O, S, N, C (even Hlg!) –if C-nucleophile then

Significance: carbon chain extension

6. Quinones and their reactions

Quinone: conjugated cyclic diketone Typical products at the oxidation ofphenols/anilines

BUT! hydrogen peroxide production

High stability, although less than forthe aromatic systems.

Preparation of oxo compounds

1. Oxidation methodsAlkene, Ar-CH3/ArCH2R oxidation only in special cases• Ozonation, or periodic acid ( HIO4) oxidation• Preparation of ArCHO: CrO2Cl2 (chromyl chloride), MnO2/H2SO4, SeO2

or

Oxidation of alcohols: 1° → RCHO 2 ° → R2C=OH2CrO4: CrO3/H2SO4-H2O (Jones), CrO3*2py (Collins), PCC=py*HCl*CrO3 (Corey) industry: Cu v. Cu2O

2. Reduction methods – Obviously, only for aldehydesDifficulty: difficult to stop at aldehyde levels

Rosemund reductionRCOCl + H2/ Pd/BaSO4

RCOOR1 + DIBAH/DIBAL-H ≡ (iBu)2Al-HLiAlH(OtBu)3

Stephen reduction (only in the case of aromatic compounds)

4. Acylation of aromatic compounds

▪ Friedel-Crafts acylation (RCOCl or (RCO)2O/Lewis-acid

Phenoles as starting materials: RCOOH/ZnCl2

▪ Gatterman-Koch (formylation of aromatic compounds, synthesis of aromatic aldehydes): CO + HCl/AlCl3+Cu3Cl2

▪ Gatterman (formylation of aromatic compounds, synthesis of aromatic aldehydes; phenoles and phenol ethers as starting materials): HCN + HCl/ZnCl2 or Zn(CN)2

▪ Houben-Hoesch (synthesis of ketones): RCN + HCl/ZnCl2

formally

only in situ

3. Organometallic CompoundsGrignard no, only with reverse addition (1 eq.) or special R2Cd reagent