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 (acetaldehyde)	2-methyl-4-hexenal
Propanal (propionaldehyde)	3-hydroxybutanal (aldol)
Butanal (butryaldehyde)	Cyclohexanecarbaldehyde
Pentanal (valeraldehyde)	Benzenecarbaldehyde (benzaldehyde)
Propenal (acrolein)

Ketone Nomenclature
1. Identify the longest continuous chain of carbons with the carbonyl carbon as on of the carbons in the chain.
2. Number the carbons so that the carbonyl carbon has the lowest possible number. If it makes no difference to the carbonyl carbon then number so that the branched groups are attached to the lowest possible carbon numbers.
3. Identify the branched groups by naming them in alphabetical order and prefixing the carbon number they are attached to onto the name. If more than one of the same group is present use the Greek prefixes (di for 2 tri for 3, etc).
4. Use the alkane name corresponding to the number of carbons in the chain and prefix the carbon number that the carbonyl carbon has to the front of the alkane name.
5. Drop the "e" in the alkane name and add the characteristic IUPAC ending for ketones which is "one".
6. When it is necessary to refer to the RCO- group as a substituent, the term acyl is used and the name ending -yl is attached. For example, CH₃CO- is an acetyl group, -CHO is a formyl group, and C₆H₅CO is a benzoyl group. If other functional groups are present and the doubly bonded oxygen is considered a substituent, the prefix oxo- is used.
 

Propanone (acetone)	2-Butanone (methy lethyl ketone)
4,4-dimethyl-2-pentanone	Acetophenone (methyl phenyl ketone)
cyclopentanone	Benzophenone
1-bromo-5-methyl-3-heptanone	Methyl-3-oxohexanoate CH3CH2CH2COCH2CO2CH3
4-hydroxy-2-cylohexenone

A. Aldehyde Synthesis
A1. Oxidation of primary alcohols by pyridinium chlorochromate (PCC) in dichloromethane.
                      PCC
R-CH₂-OH  ----------->   R-CHO
1^o alcohol     CH₂Cl₂          Aldehyde

A2. Alkenes with at least one vinylic hydrogen undergo oxidative cleavage when treated with ozone.
                                 1. ozone
1-methylcyclohexene -----------------> 6-oxoheptanal
                                  2. Zn, HAc

A3. Esters are partially reduced by diisobutylaluminum hydride (DIBAH), normally at -78^oC (dry-ice temperature) in toluene.
                    1. DIBAH, toluene, -78^oC
R-CO₂R’ ----------------------------------> RCHO
Ester            2. H₃O⁺                                     Aldehyde

B. Ketone Synthesis
B1. Secondary alcohols are oxidized by a variety of reagents such as PCC.
                        PCC
R-CHOH-R --------------> R-CO-R
2^o alcohol        CH₂Cl₂         Ketone

B2. Ozonolysis of alkenes yields ketones if one of the unsaturated carbon atoms is disubstituted.
                     1. ozone
CR₂=CH₂ ----------------> R-CO-R  +  H₂CO
                     2. Zn, HAc

B3. Aryl ketones are prepared by Friedel-Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl₃.
                                                ACl₃
Ar       +      RCOCl             -----------> Ar-CO-R
Aromatic     Acid Chloride      Heat

B4. Methyl ketones are prepared by hydration of terminal alkynes in the presence of Hg²⁺.
                        H₃O⁺
R-C=CH     ------------> RCOCH₃
Alkyne         HgSO₄         Methyl Ketone

B5. Certain carboxylic derivatives can be converted to ketones by using such reagents as dimethylcopperlithium reacting with acid chlorides.
R-COCl       + (CH₃)₂CuLi   --------------------> RCOCH₃
Acid chloride     Dimethyl copper lithium                   Ketone

Rxns of Aldehydes and Ketones
A. Oxidation of Aldehydes: Aldehyde + [O] -----> carboxylic acid
[O] = HNO₃, KMnO₄, Jones reagent [CrO₃ in aqueous acid], Tollens reagent [Ag₂O in aqueous ammonia].
                           CrO₃, H₃O⁺
RCHO         -------------------->   RCO₂H
Aldehyde             Acetone, 0^oC    Carboxylic acid

Tollens reagent leaves C=C bonds and other functional groups.
                    AgO₂
PhCHO    ------------------------>    PhCO₂H
Aldehyde     NH₄OH, H₂O, EtOH     Carboxylic acid

B. Oxidation of Ketones: Ketone + [O] ----> NR
Ketones are inert to most oxidizing agents but undergo a slow cleavage to carboxylic acids reaction when treated with hot alkaline KMnO₄.
                1. KMnO₄, NaOH(aq), Heat
Acetone -----------------------------------> 2 Acetic acid
               2. H₃O⁺

                           1. KMnO₄, NaOH(aq), Heat
Cyclohexanone -----------------------------------> Hexanedioic acid
                         2. H₃O⁺

C. Nucleophilic Addition Rxns of Aldehydes and Ketones
C1. Nucleophilic Addition of Water: Hydration
>C=O + water -----> gemdiol
Rxn favors starting materials.

C2. Nucleophilic Addition of HCN: Cyanohydrins
RCHO + HCN ---> RCH(OH)CN (cyanohydrin)

Nitriles (RCN) can be reduced with LiAlH₄ to yield primary amines
                             1. LiAlH₄, THF
RCH(OH)CN --------------------------> RCH(OH)CH₂NH₂
                            2. H₂O

and can be hydrolyzed by hot aqueous acid to yield carboxylic acids.
                            H₃O⁺, Heat
RCH(OH)CN -----------------> RCH(OH)CO₂H

C3. Nucleophilic Add’n of Grignard & Hydride Reagents: Alcohol Formation
C3a. Formaldehyde + Grignard -----> 1^o alcohol
               1. CH₃MgCl, Et₂O
H₂CHO -----------------------> CH₃CH₂OH
               2. H₃O⁺

C3b. Aldehyde + Grignard -----> 2^o alcohol
                 1. PhMgCl, Et₂O
CH₃CHO -----------------------> CH₃CH(OH)Ph
                 2. H₃O⁺

C3c. Ketone + Grignard -----> 3^o alcohol
                       1. PhMgCl, Et₂O
CH₃COCH₃ -----------------------> (CH₃)₂C(OH)Ph
                       2. H₃O⁺

C3d. >C=O + LiAlH₄ or NaBH₄ -----> alcohol
Reducing agents such as lithium aluminum hydride (LiAlH₄), sodium borohydride (NaBH₄), or hydrogen and a catalyst.
Benzaldehyde + LiAlH₄ ---> Benzyl alcohol
Cyclohexanone + NaBH₄ ---> Cyclohexanol
                                Pt
Acetaldehyde + H₂ ----> Ethanol

C4. Nucleophilic Addition of Amines: Imine and Enamine Formation
>C=O + 1^o amine -----> Imine
>C=O + 2^o amine -----> Enamimine
Net result is the substitution of O by N of the amine.
Primary amines, RNH₂, react with aldehydes and ketones to yield imines, RN=C(R)₂.
Hydroxylamine, NH₂OH, yield oximes
Semicarbazide, NH₂NHCONH₂, yield semicarbazones
2,4-dinitrophenylhydrazine yield 2,4-dinitrophenylhydrazones (2,4-DNP's)
Secondary amines, R₂NH, react to yield enamines, R₂N-C=C<

C5. Nucleophilic addition of Hydrazine: The Wolff-Kishner Reaction
Converts aldehydes or ketones to alkanes
             H₂NNH₂, KOH
>C=O --------------------------> >CH₂

C6. Clemmensen reduction accomplishes the same using amalgamated zinc, Zn(Hg), and concentrated HCl. Used when starting materials are sensitive to base.
                Zn(Hg)
>C=O --------------->   >CH₂
                HCl, Heat

C7. Nucleophilic Addition of Alcohols: Acetal Formation
>C=O + 2 ROH -----> >C(OR)₂ acetal
One mole of carbonyl plus 2 moles of alcohol.
Rxn of carbonyl with ethylene glycol (HOCH₂CH₂OH) yields a cyclic acetal.
Acetals are useful because they can serve as protecting groups for aldehydes and ketones in the same way that trimethylsilyl ethers serve as protecting groups for alcohols.

C8. Nucleophilic Addition of Phosphorous Ylides: The Wittig Reaction
Ketones and aldehydes are converted to alkenes by reaction with a phosphorus ylide, R₂C^--P⁺(C₆H₅)₃.
>C=O + (R)₂C^--P⁺(C₆H₅)₃ -----> >C=C(R)₂
The net result is replacement of the carbonyl oxygen atom by the R₂C= group.

D. The Cannizzaro reaction
Aldehydes with no a hydrogens (i.e. formaldehdye and benzaldehydes) when heated with hydroxide yield one equivalent of carboxylic acid and one equivalent of alcohol.
                   1. OH^-
2 PhCHO ------------->  PhCO₂H  +  PhCH₂OH
                  2. H₃O⁺

E. Conjugate Nucleophilic Addition to a,b-Unsaturated carbonyl Groups
The net effect is addition of the nucleophile to the b-carbon of the C=C double bond, with the carbonyl group itself unchanged.
E1. Conjugate Addition of Amines
Primary and secondary amines add to a,b-unsaturated carbonyl compounds to yield b-amino carbonyl compounds.

E2. Conjugate Addition of Alkyl Groups: Organocopper Reactions
Conjugate addition of an alkyl group to a,b-unsaturated ketone is carried out by treating the ketone with lithium diorganocopper reagent (Gilman reagent). Primary, secondary, and even tertiary alkyl groups work as do aryl and alkenyl groups.

Spectroscopic Analysis of Ketones and Aldehydes
IR
Aldehydes and ketones show a strong C=O bond absorption in the infrared region from 1660 to 1770 cm^-1.
Aldehydes show two characteristic C-H absorptions in the infrared region from 2720 -2820^-1.

NMR
Aldehydic protons – 10d
There is spin-spin coupling of the aldehydic proton.
a-carbon hydrogens are deshielded and absorb 2.0-2.3d.
methyl ketones show a characteristic three-proton singlet near 2.1d.

Mass Spectroscopy
Aliphatic aldehydes and ketones that have hydrogens on the gamma (g) carbon atoms undergo a spectral cleavage (McLafferty rearrangement.)

Nature of The Carboxyl Group
The functional group present in organic acids is known as the carboxyl group.
The carboxyl group can be symbolized as -COOH or -CO₂H.

Nomenclature
Acids derived from open chain alkanes: replace -e with -oic acid.
Acids with -COOH bonded to a ring: use the suffix -carboxylic acid.

Structure                Systematic Name            Common Name
HCO₂H                 Methanoic acid                Formic acid
CH₃CO₂H             Ethanoic acid                   Acetic acid
CH₃CH₂CO₂H      Propanoic acid                 Propionic acid
C₆H₄CO₂H            Benzoic acid

Structure and Physical Properties of Carboxylic Acids
Strongly associated due to hydrogen bonding.

Carboxylic acids with more than six carbons are only slightly soluble in water.
Alkali metal salts are generally quite water soluble.
For most carboxylic acids, K_a = approximately 10^-5.    Acetic acid K_a = 1.76 x 10^-5.
 K_a values near 10^-5 mean only about 0.1% of the molecules in a 0.1 M solution are dissociated as opposed
to the 100% dissociation found with strong mineral acids such as HCl.

Stabilization of carboxylate anion increases acidity and vice versa.
Electron withdrawing groups (e.g. halogen) (EAS deactivators) increase acidity.
Electron donating groups (e.g.-R,-OR) (EAS activators) decrease acidity.

Synthesis of Carboxylic Acids
A.   Oxidation of substituted alkylbenzenes (Ph-R) with KMnO₄ or Na₂Cr₂O₇ yield benzoic acids.
    R = only 1^o or 2 ^o. 3 ^o groups are not affected.
                1. KMnO₄, OH^-, Heat
    Ph-R -----------------------------> Ph-CO₂H
                2. H₃O⁺
B. Alkenes with at least one vinylic hydrogen are oxidatively cleaved with KMnO₄ to produce carboxylic acids. If the other carbon of the alkene has two hydrogens it produces carbon dioxide.
                            1. KMnO₄
    RCH=CH₂ --------------------> R-CO₂H + CO₂
                            2. H₃O⁺
C. Oxidation of 1^o alcohols and aldehydes. Alcohols by Jones' reagent (CrO₃, H₂O, H₂SO₄). Aldehydes by Jone’s or Tollens' reagent.
                        CrO₃, H₂O,
    RCH₂-OH ------------------> RCO₂H
                        H₂SO₄

                 CrO₃, H₃O⁺
RCHO -----------------------> RCO₂H
                Acetone, 0^oC

D. Hydrolysis of nitriles by either hot aqueous acid or base.

                H₃O⁺, Heat   or    OH^-, Heat
R-CN ----------------------------------------> RCO₂H

E. Carboxylation of Grignard reagents
               1. CO₂, Et₂O
RMgX -----------------> RCO₂H
                2. H₃O⁺

Reactions of Carboxylic Acids
A.   Deprotonation               Acid + Base ----> Salt
The sodium and potassium salts of long-chain acids (fatty acids) are referred to as soaps.
RCO₂H + NaOH -----> RCO₂^-Na⁺ + H₂O
 

B.   Reduction
Reduction by LiAlH₄, THF, and Heat yields primary alcohols.

                1. LiAlH₄, THF, Heat
RCO₂H ------------------------------> RCH₂OH
                2. H₃O⁺

Borane in tetrahydrofuran (BH₃/THF) at room temp. Nitro groups or carbonyls are not reduced by this method.
                1. BH₃, THF
RCO₂H ------------------------> RCH₂OH
                2. H₃O⁺

(NaBH₄ does not reduce carboxylic acids.)

Suggested problems for Chapter 20 Carboxylic Acids
20.17; 20.19; 20.20; 20.22; 20.23; 20.24; 20.29; 20.31; 20.32; 20.34