Aldehydes and Ketones
Nature of The Carbonyl Group
The carbonyl group consists of a carbon double bonded to an oxygen.
     >C=O

Similar to alkenes
- >C=C< >C=O
- carbon is sp2 hybridized
- 120o bond angles
- planar about the double bond

Polar
  d+ d-    +      -
>C==O « >CO

- C is electrophilic
- O is nucleophilic

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
1o 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 -78oC (dry-ice temperature) in toluene.
                    1. DIBAH, toluene, -78oC
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
2o 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, 0oC    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 Addn of Grignard & Hydride Reagents: Alcohol Formation
C3a. Formaldehyde + Grignard -----> 1o alcohol
               1. CH3MgCl, Et2O
H2CHO -----------------------> CH3CH2OH
               2. H3O+

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

C3c. Ketone + Grignard -----> 3o 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 + 1o amine -----> Imine
>C=O + 2o 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.)


CARBOXYLIC ACIDS

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, Ka = approximately 10-5.    Acetic acid Ka = 1.76 x 10-5.
 Ka 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 1o 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 1o alcohols and aldehydes. Alcohols by Jones' reagent (CrO3, H2O, H2SO4). Aldehydes by Jones or Tollens' reagent.
                        CrO3, H2O,
    RCH2-OH ------------------> RCO2H
                        H2SO4

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

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 19 Aldehydes and Ketones
19.25; 19.26; 19.27; 19.28; 19.29; 19.30; 19.31; 19.32; 19.34; 19.37; 19.38; 19.43; 19.44

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