Organic II Test 3
Compounds containing carbonyl groups undergo what two types of reactions?
1. Nucleophilic addition
2. Nucleophilic substitution
Which is more reactive, aldehydes or ketones?
The first step of nucleophilic addition is:
The second step of nucleophilic addition is:
The first step of nucleophilic substitution is:
The second step of nucleophilic substitution is:
Loss of leaving group
Most useful agents for reducing aldehydes and ketones
1. Sodium borohydride (NaBH)
2. Lithium aluminum hydride (LiAlH)
3. Polar metal H-bond
Reduction reactions start with ___ C-O bond(s) and end with ___ C-O bond(s).
A ketone reacting with NaBH4 or CH3OH yields -->
A ketone reacting with H2 in the presence of excess Pd-C yields -->
A ketone reacting with H2 yields -->
Redox reactions of carbonyl compounds yields a __:__ mixture.
Treatment of a ketone or aldehyde with a halogen (X) and either acid or base results in substitution of __ for __ on a alpha-C.
Example of a chiral reducing agent:
*used in the presence of H2O
(R)-CBS or (S)-CBS
(R)-CBS yields -->
(S)-CBS yields -->
(S) = minor
(R) = major
A biological reducing agent is:
Mild reducing agents:
Acid halides and esters convert to either _________ or _________, depending on the reagent.
aldehyde, 1-degree alcohol (Ex. RCH2OH)
LiAlH4 reduces carboxylic acids to:
LiAlH4 reduces amides to:
Reagents used for oxidation of aldehydes:
General structure of organometallic reagent:
C bonded to a metal (R-M)
Most common metals used in organometallic reagents:
Li, Mg, Cu
The more polar the metal, the ____ reactive the reagent.
Organometallic reagents are _____ bases that readily abstract a proton from water to form hydrocarbons.
Aldehydes and ketones form ________ in the presence of organometallic reagents.
Carboxylic acid derivatives form ________ or ________ in the presence of organometallic reagents.
ketones or alcohols
Other functional groups form ________ or _________in the presence of organometallic reagents.
Carboxylic acids or alcohols
3 step strategy for protecting groups:
1. Convert OH into another functional group that does not interfere
2. Carry out reaction
3. Remove protecting group
Common OH protecting group:
Organocuprates are _____ reactive organometallics.
General structure for organocuprate:
Grignard reagents react with CO2 to produce:
Preparation of aldehydes involves oxidation of a ___________ with __________.
1-degree alcohol, PCC
Cyclohexone reacting with NaBH4/LiAlH4 in the presence of H2O yields -->
Cyclohexone reacting with RMgX/RLi in the presence of H2O yields -->
Cyclohexone reacting with -CN in the presence of HCl yields -->
Cyclohexone reacting with Ph3P+--CR2 yields --> oxaphosphetene which reacts with -Ph2P=O to yield -->
Cyclohexone reacting with RNH2 (1-degree amine) in the presence of a mild acid yields --> carbinolamine, which in the presence of H2O yields -->
Cyclohexone reacting with R2NH (2-degree amine) in the presence of a mild acid yields --> cabinolamine, which in the presence of H2O yields -->
Cyclohexone reacting with ROH, H+ yields --> hemiacetal -->
An alkene reacts with O3 in the presence of Zn/H2O or CH3SCH3 to yield _________ and _________.
Witting reactions use C nucleophiles for form __________.
In a witting reaction, the carbonyl group is converted to a _____________.
The two resonance structures of the Witting reagent are:
Treatment of an aldehyde or ketone with a 1-degree amine yields -->
Imines are classified as 1-, 2-, or 3-degree based on the number of ______ groups bonded to the N atom
An imine has a bond angle of:
Imines form fastest when reaction medium is weakly _______.
Treatment of an aldehyde or ketone with a 2-degree amine yields -->
General structure of enamine:
General structure of imine:
Imines and enamines can be converted back to carbonyl compounds by reacting with _____.
Treatment of carbonyl compounds with H2O in the presence of acid or base catalysts adds H and OH across the C-O pi bond to form a __________.
Aldehydes and ketones react with 2 equivalents of alcohol in the presence of H+ to form:
General structure of acetal:
R -- C -- R'
Aldehydes and ketones react with 1 equivalent of alcohol in the presence of H+ to form:
General structure of hemiacetals:
Reacting a ketone with a vicinal diol (OH on different Cs) yields -->
Three types of anhydrides:
1. Symmetrical (both R groups identical)
2. Unsymmetrical (R groups different)
3. Cyclic (R groups are two points on cyclic compound)
To name an acyclic acid chloride, change suffix -ic acid of parent carboxylic acid to suffix ___ __________.
-Ex. Acetic acid -->
--> Acetyl chloride
To name an anhydride, change suffix acid to _________.
-Ex. Acetic acid -->
--> Acetic anhydride
To name an ester, follow these steps:
1. Name R' group bonded to O atom as an alkyl group
2. Name acyl group (RCOO-) by changing the -ic acid of parent carboxylic acid to -ate
To name a 1-degree amine, replace the suffix with _______.
-Ex. Acetic acid -->
Anhydride + H2O -->
Anhydride + R'OH (alcohol) -->
Anhydride + 2 NH3 -->
RCOOH (carboxylic acid) + SOCl2 -->
RCOCl (acyl chloride) + SO2 + HCl
The reaction of a carboxylic acid (RCOOH) and an alcohol (ROH) in the presence of H2SO4 is called _______ ___________.
R-COOH + R-OH + H2 SO4 -->
R-COOR + H2O
DCC (dicyclohexylcarbodimine) is a(n) __________ agent.
Structure of DCC:
When ester is hydrolized with water in the presence of acid, it yields -->
When ester is hydrolized with water in the presence of base, it yields -->
Esters react with NH3 and amines to form:
1-, 2-, and 3- amines
Amides are the _____ reactive derivatives.
Amides in the presence of acid yield-->
Carboxylic acid and ammonium (by-product)
Amides in the presence of a base yield -->
Ester anion and neutral amine (by-product)
General structure of a nitrile:
Nitriles are prepared by the SN2 reaction of:
unhindered methyl and 1-degree alkyl halides with -CN
Hydrolysis of nitriles in the presence of acid yields -->
Hydrolysis of nitriles in the presence of a base yields -->
Reduction of a nitrile with LiAlH4 yields -->
Reduction of a nitrile with DIBAL-H yields -->
Reduction of a nitrile with an organometallic reagent yields -->
Reactions at the C alpha to the carbonyl group proceed by way of ________ and __________.
General structure of an enol:
General structure of an enolate:
In keto-enol tautomerization, equilibrium favors _________.
In 1,3-dicarbonyl compounds, equilibrium favors __________.
pKa value of C-C:
pKa value of CH2=CHCH3:
pKa value of (CH3)2C=O:
pKa value of CH3-CH2-OH:
pKa of CH3-CO2-H:
pKa of amide:
pKa of nitrile:
pKa of ester:
pKa of ketone:
pKa of aldehyde:
pKa of 1,3-diester:
pKa of 1,3-dinitrile:
pKa of B-keto ester:
pKa of B-diketone:
pka of H2O:
LDA quickly ________________ all carbonyl starting materials.
pKa of diisopropylamine:
For unsymmetrical carbonyls, two enolate paths are possible:
1. 2-degree removal
2. 3-degree removal
For unsymmetrical carbonyls, the removal of the __-degree H is faster.
For unsymmetrical carbonyls, the removal of the __-degree H is more stable.
Removal of the 2-degree H in unsymmetrical carbonyls is a ________ process.
Removal of the 3-degree H in unsymmetrical carbonyls is a _________ process.
3 conditions favoring kinetic enolates:
1. Strong nucleophilic base (LDA) --> ensures enolate forms rapidly
2. Polar aprotic solvent (THF) --> dissolves starting materials
3. Low temperatures --> -78 C
3 conditions favoring thermodynamic enolates:
1. Strong base
- Na+ -OCH2CH3
- K+ -OC(CH3)2
2. Polar protic solvent (CH3CH2OH)
3. Room temperature
Treatment of a ketone of aldehyde with a halogen (X) and either acid or base results in substitution of __ for __ on a alpha-C.
Treatment of a ketone or aldehyde with a halogen (X) in the presence of acid requires two steps:
1. tautomerization of the carbonyl compound to the enol form
2. reaction of enol with halogen
Treatment of a ketone or aldehyde with a halogen (X) in the presence of a base is _____ useful.
When a ketone or aldehyde is treated with X2 in the presence of an acid -->
one alpha-H is replaced with X
When a ketone or aldehyde is treated with X2 in the presence of a base -->
both alpha-H are replaced with X
Methyl ketone + X2 (excess) + -OH -->
Carboxylate anion + CHX3 (haloform)
General structure of haloform:
Treatment of an aldehyde or ketone with a base and alkyl halide results in ____________.
Four steps of malonic ester synthesis:
1. Form enolate
2. SN2 reaction
3. Hydrolysis of ester
4. Remove CO2
Malonic ester synthesis converts diethyl malonate to __________ ______.
Four steps of acetoacetic ester synthesis:
Two molecules of an aldehyde or ketone react with each other in the presence of a(n) _______ to form a B-hydroxy carbonyl compound.