Ochem 2 Flashcards
- Aldehydes & Ketones
- Formation of Acetals/Hemiacetals and Ketals/Hemiketals
- Describe the 4 steps of formation
- Formation of Acetals/Hemiacetals and Ketals/Hemiketals
- An alcohol acts as the nucleophile
- Attacking the electrophilic carbonyl carbon and
- pushing the pi electrons from the C=O bond up onto the oxygen
- The negatively charged oxygen is protonated to form an alcohol and
- the original alcohol is deprotonated to form an ether
- This yields:
- a hemiacetal if it was originally an aldehyde, or
- a hemiketal if it was a ketone
- This yields:
- The alcohol is protonated again to form the good leaving group water
* a second equivalent of alcohol attacks the central carbon - Deprotonation of the second alcohol results in another ether,
- yielding:
- an acetal if it was originally an aldehyde
- or a ketal if it was a ketone
- Acid (Acyl) Chloride
- Acid Chloride Formation
- Formula=?
- What 3 reagents readily produce acid chlorides when added to carboxylic acids?
- Acid Chloride Formation
RCOOH + PCl3 ⇒ RCOCl + H2O
- Three reagents readily produce acid chlorides when added to carboxylic acids:
- PCl3
- PCl5
- SOCl2
- Acid Chloride
- Acid Chloride Formation
- Addition of chloride ion (Cl-) to a carboxylic acid does NOT produce an acid chloride
- Provide a possible explanation for WHY
- Acid Chloride Formation
- A chloride ion IS capable of attacking the carbonyl carbon of a carboxylic acid
- However, when the electrons in the carbonyl bond are kicked up onto the oxygen, and then collapse back down, the substituent that is the best leaving group will leave
- …regardless of the original structure of the molecule
- However, when the electrons in the carbonyl bond are kicked up onto the oxygen, and then collapse back down, the substituent that is the best leaving group will leave
- Chloride ion is more stable (i.e., it is a weaker base) than hydroxide ion
- so the chlorine will be kicked off to reform the acid
- Acid Chlorides (a.k.a.___)
- Definition
- Nomenclature
- Common Names (3)
Definition:
- An acid chloride (a.k.a. “acyl chloride”) is any compound containing:
- a carbonyl
- with a chlorine substituent on the carbonyl carbon
- a carbonyl
Nomenclature:
- Acid chlorides are named with the “–oyl chloride” suffix
- Ex: propanoyl chloride
Common Names:
- Know the same three non-IUPAC names we’ve been highlighting for each functional group
- Formyl chloride
- Acetyl chloride
- BenzOYL chloride
Take note that benZYL chloride is NOT an acid chloride
- It is a chlorine attached to a benzyl group
- Acid Chloride
- What property of Acid Chlorides make them IMPORTANT?
- What 2 things are the cause of this property?
- Acid Chlorides are important because:
- they are the most reactive of the carboxylic acid derivatives
- Their reactivity is due to:
- The withdrawing power of the chlorine
- which makes the partial positive charge on the carbonyl larger than normal
- The fact that chloride ion is a superb LG
- The withdrawing power of the chlorine
- Acid Chlorides
- Provide a reactant that will form each of the following when reacted with an acid chloride
- An ester
- An amide
- An anhydride
- A carboxylic acid
- Provide a reactant that will form each of the following when reacted with an acid chloride
- ROH
- RNH2
- RCOOH
- H2O
- Aldehydes & Ketones
- General Characteristics
- Why don’t aldehydes and ketones undergo substitution reactions?
- ex: SN1, SN2
- Why don’t aldehydes and ketones undergo substitution reactions?
- General Characteristics
In order for a substitution to occur, there must be a LEAVING GROUP
-
Acid derivatives all have leaving groups:
- Cl- in the case of acid chlorides
- -OH in the case of carboxylic acids
- a Carboxylate ion in the case of anhydrides, etc.
- The stability of these groups after they leave varies widely, but in the case of an aldehyde or ketone:
- there are NO groups that would be reasonably stable,
- and therefore NO candidates to act as leaving groups
- The aldehyde hydrogen will not leave as H:- , nor will an R group leave from a ketone as a carbanion R:-
- In both cases, the leaving group would become a strong base
- Recall that strong bases** **NEVER** **make good leaving groups
- Good leaving groups must be WEAK bases that are stable AFTER they leave
- For this reason, aldehydes and ketones only undergo addition reactions—lacking a suitable leaving group to undergo substitution
- Recall that strong bases** **NEVER** **make good leaving groups
- Aldehydes & Ketones
- General Characteristics
- Aldehydes and ketones can also function as Lewis ___s, accepting electrons when WHAT happens?
- General Characteristics
- Aldehydes and ketones can also function as Lewis ACIDS, accepting electrons when
- a base abstracts an alpha hydrogen
- Aldehydes & Ketones
- Aldol Condensation
- Describe
- Explain the 3 steps
- Aldol Condensation
Aldol Condensation
- The condensation of one aldehyde or ketone with another aldehyde or ketone
STEPS:
- A base abstracts an alpha hydrogen, creating a carbanion
- The carbanion will attack any carbonyl carbon in the solution
- The oxygen is protonated to form an alcohol
- Aldehydes & Ketones
- Aldol Condensation
- What’s a common mistake students make with aldol condensations?
- How can you avoid this mistake?
- Aldol Condensation
THE MCAT LOVES ALDOL CONDENSATIONS!
The common mistake seems to be for students to lose track of the carbanion carbon—often drawing a product with the two original carbonyl carbons adjacent to one another
To avoid this:
- Always draw out the product
- Do NOT try to predict it in your head
- Draw the carbanion nearby the carbonyl and then immediately draw a bond between them
In the product there should always be one carbon in between:
- the carbonyl carbon
- the carbon bearing the hydroxyl group
This could also be avoided by counting the total carbons before and after the reaction
- Aldehydes & Ketones
- α-β Unsaturated Carbonyls
- Describe
- Is an α-β unsaturated carbonyl a base, a nucleophile, or an electrophile?
- α-β Unsaturated Carbonyls
An aldehyde or ketone with a double bond between the alpha and beta carbons
- In terms of the MCAT, you should think of an α-β-unsaturated carbonyl as an ELECTROPHILE
- It might be tempting to think of the double bond between the alpha and beta carbons as a nucleophile that will undergo electrophilic addition
- However, the withdrawing effect of the carbonyl decreases the electron density of the double bond deactivating it toward electrophilic addition
- Anhydrides
- Definition
- Nomenclature
- Common Names (3)
Definition:
- An anhydride is a compound with two acyl groups connected to one another by a single oxygen
- Viewed another way, an anhydride is an ester where the –R group is a carbonyl
Nomenclature:
- Named by replacing the “-oic” ending of the corresponding carboxylic acid with “-oic anhydride”
- i.e., benzoic acid⇒benzoic anhydride
- Mixed acid anhydrides are named alphabetically
- i.e., ethanoic methanoic anhydride
Common Names:
- The MCAT will expect you to recognize:
- formic anhydride
- acetic anhydride
- acetic formic anhydride
- If it is a mixed anhydride made from:
- ethanoic acid and methanoic acid
- Aldehydes & Ketones
- General Characteristics
- Which is more acidic, the alpha hydrogen of a ketone, or the alpha hydrogen of an aldehyde?
- Provide a possible explanation
- General Characteristics
The alpha hydrogen of an aldehyde is more acidic than a comparable alpha hydrogen on a ketone
- because the conjugate base in the case of the aldehyde is more stable
In an aldehyde, a hydrogen is attached to the carbonyl carbon
- Hydrogen is defined as neither a withdrawing group nor a donating group
However, in the case of a ketone, an –R group is attached to that same carbonyl carbon
- and –R groups are weakly electron donating
- This will decrease the magnitude of the partial positive charge on the carbonyl carbon in the ketone
- making it less able to stabilize the negative charge of the carbanion in the conjugate base
- This will decrease the magnitude of the partial positive charge on the carbonyl carbon in the ketone
- Aldehydes & Ketones
- General Characteristics
- Substitution vs. Addition
- Aldehydes & Ketones undergo…?
- What 4 FG’s undergo nucleophilic SUBSTITUTION?
- Substitution vs. Addition
- General Characteristics
Aldehydes and Ketones undergo:
- nucleophilic ADDITION
- Carboxylic Acids
- Amides
- Esters
- Anhydrides
undergo. ..
* nucleophilic SUBSTITUTION
- Aldehydes & Ketones
- General Characteristics
- MAJOR FUNCTION=?
- General Characteristics
ELECTROPHILES!
with their carbonyl carbon being attacked by Nu:’s
Aldehydes & Ketones
-
Halogenation of an Aldehyde or Ketone
- Describe
- List the 2 steps
- Substitution of a Br, Cl or I for one of the alpha hydrogens on an aldehyde or ketone
- Multiple halogenations often occur
STEPS:
- A base abstracts an alpha hydrogen
- leaving a carbanion
- The carbanion attacks a diatomic halogen (Br2)
- Aldehydes & Ketones
- Keto-Enol Tautomerization
- Aldehydes and ketones cannot act as H-bond donors
- An exception to this rule is 1,3-dicarbonyl compounds
- They can act as hydrogen bond donors
- An exception to this rule is 1,3-dicarbonyl compounds
- Draw out a 1,3 dicarbonyl compound and propose an explanation
- Aldehydes and ketones cannot act as H-bond donors
- Keto-Enol Tautomerization
A 1,3-dicarbonyl can undergo an intramolecular hydrogen bond when:
- one of the carbonyls is in the keto form and
- the other is in the enol form
- This significantly stabilizes the enol compared to a stand-alone enol
- In this condition:
- the enol is acting as the hydrogen-bond donor
- the carbonyl as the hydrogen bond acceptor
The MCAT loves alpha hydrogens so much, it wouldn’t be right to mention 1,3-dicarbonyls without also pointing out that they have ULTRA ACIDIC alpha protons on the carbon between the two carbonyl carbons
- b/c there’s DOUBLE resonance stabilization!
- Aldehydes & Ketones
- Keto-Enol Tautomerization
- Draw a step-wise mechanism for the tautomerization
- Keto-Enol Tautomerization
- Aldehydes & Ketones
- Keto-Enol Tautomerization
- Which is more stable, the keto or the enol tautomer?
- Why?
- Keto-Enol Tautomerization
The keto and enol forms are in an equilibrium with one another that strongly favors the keto form at room temperature
- The keto form is more stable
- because the sum of its bond energies is greater than the sum of the bond energies in the enol form
- The keto form has a C=O bond, a C-C bond, and a C-H bond
- that are replaced by a C-O bond, a C=C bond, and an O-H bond in the enol form
- C-H and O-H bonds are quite close in bond energy
- C=C has about 250 kJ/mol more bond energy than a C-C bond (almost double)
- The real difference comes in the difference between a C-O bond and a C=O bond
- A C=O bond has about 450 kJ/mole more bond energy!
- What you should know is that carbonyl bonds are much shorter and stronger than alkene bonds
- That is the most significant difference between the two forms and is the reason the keto form is favored.
- Aldehydes & Ketones
- Nomenclature
- There are a few common aldehydes and ketones for which the MCAT will use non-IUPAC names
- Name the 4 we need to know
- Hint: FABA
- There are a few common aldehydes and ketones for which the MCAT will use non-IUPAC names
- Nomenclature
- There are a few common aldehydes and ketones for which the MCAT will use non-IUPAC names
- These include:
-
formaldehyde
- HCOH
-
acetaldehyde
- CH3COH
-
benzaldehyde
- C6H5COH
-
acetone
- CH3COCH3
-
formaldehyde
- These include:
- Aldehydes & Ketones
- Nomenclature
- What suffixes are they associated with each?
- If a ketone must be named as a FG, what suffix does it use?
- What must the parent chain contain?
- Nomenclature
Aldehydes
- are named with the “–al” ending
- Aldehyde carbons are always considered carbon #1 for numbering purposes
Ketones
- are named with the “–one” ending
- If a ketone MUST be named as a substituent, it is called an “-oxo” group
- as in 4-oxopentanal
In either case, the parent chain must be the longest chain that includes the carbonyl
Aldehydes & Ketones
- Ketones are given the name “-oxo” as substituents
- What is an aldehyde named if it must be labeled as a substituent?
- Aldehydes and ketones can ONLY be substituents when WHAT is present?
- If the aldehyde or ketone is the TOP priority functional group:
- Which Carbon is labeled as C-1?
Surprisingly, substituent aldehydes are given the SAME “-oxo” name as ketone substituents!
There really should not be any confusion, however, because:
- if the identified carbon is TERMINAL:
-
it MUST be an aldehyde
- and cannot be a ketone
-
it MUST be an aldehyde
- and if it is SECONDARY:
-
it MUST be a ketone
- and cannot be an aldehyde
-
it MUST be a ketone
Remember that aldehydes and ketones can ONLY be substituents when:
- there is a HIGHER priority functional group present*
- such as a carboxylic acid
If the aldehyde or ketone is the *TOP* priority functional group:
then the carbonyl carbon is always labeled as C-1
- Aldehydes & Ketones
- Physical Properties
- Solubility & BP trends
- Aldeyhdes and ketones can act as _____recipients, but NOT as____donors
- Solubility & BP trends
- Physical Properties
- Aldeyhdes and ketones can act as H-bond recipients, but NOT as H-bond donors
- Aldehydes & Ketones
- Physical Properties
- Solubility & BP trends
- Use your knowledge of structure and function to predict the relative water solubility of aldehydes and ketones compared to comparable alkanes or alcohols
- How will boiling point differ between these same species?
- Solubility & BP trends
- Physical Properties
SOLUBILITY:
Alkanes
- Alkanes are non-polar and therefore insoluble in water
- Aldehydes and ketones can act as hydrogen-bond acceptors when dissolved in water, with water acting as the hydrogen bond donor
- Therefore, aldehydes and ketones will be far more soluble than alkanes
- Finally, alcohols can hydrogen bond as both a donor and acceptor with water, so they will be the most soluble
- These trends assume comparable molecular weight, chain length, etc
- This is important because a small alcohol such as methanol is water soluble, but dodecanol (big) is considered insoluble
- These trends assume comparable molecular weight, chain length, etc
BOILING POINTS
Alkanes
- The boiling point of alkanes will be the lowest
- because their only intermolecular attraction would be van der Waals forces
- Aldehydes and ketones do NOT hydrogen bond with one another
- but they are both polar and will therefore have much higher boiling points than alkanes
- Finally, alcohols will have the highest boiling points
- due to intramolecular hydrogen bonding (Strong IMFs)
- Aldehydes & Ketones
- Keto-Enol Tautomerization
Keto-Enol Tautomerization:
- This is the process by which an alpha hydrogen adjacent to an aldehyde or ketone becomes bonded to the carbonyl oxygen,
- ……while the double bond is switched from the carbonoxygen bond to the bond between the carbonyl carbon and the alpha carbon
- Aldehydes & Ketones
- α-β Unsaturated Carbonyls
- What are the 2 possible ways to visualize this mechanism?
- α-β Unsaturated Carbonyls
STEPS:
- There are two possible ways to visualize this mechanism, based on which resonance form you start with:
- With the double bond between the alpha and beta carbons, the nucleophile attacks the beta carbon
- pushing the double bond over one carbon and forcing the C=O electrons up onto the oxygen
- With a carbocation on the beta carbon, the nucleophile simply attacks the beta carbon directly
- Starting with either resonance form, the oxygen will get protonated to form an alcohol
- Note that the protonated oxygen is really just the enol form of a keto-enol tautomer
- Aldehydes & Ketones
- α-β Unsaturated Carbonyls
- Draw two possible resonance structures for an α-β unsaturated carbonyl
- Which one will be the major contributor to the resonance hybrid?
- α-β Unsaturated Carbonyls
- The one on the left is clearly the more significant contributor to the actual structure
- because it has no formal charges, compared to a charge separation in the structure on the right
- Aldehydres & Ketones
- Define
Aldehyde
- is any compound containing a carbonyl…
- with one or more hydrogen substituents on the carbonyl carbon
Ketone
- is any compound containing a carbonyl…
- with two carbon substituents on the carbonyl carbon
- Amide
- Properties
- Among acid derivatives, amides are…?
- Describe the reactivity of an amide’s carbonyl carbon
- Properties
- Amides are theMOST STABLE of all acid derivatives
- Their carbonyl carbons are UNreactive
- This is because –NH2 is NOT a good leaving group
- Their carbonyl carbons are UNreactive
- Amide
- Properties
- 1° and 2º amides can do what?
- What about 3º amides?
- What is the BIOCHEMISTRY connection here?
- Properties
- Primary and secondary amides can HYDROGEN BOND
- ∴ amides are water soluble as long as:
- they lack long alkyl chains
- ∴ amides are water soluble as long as:
- Tertiary amides cannot H-bond
Biochemistry Connection:
- Amide hydrogen bonding is perfectly illustrated in the secondary structure of proteins
- In an alpha helix every amine hydrogen forms an H-bond with the carbonyl four residues previous to it in the chain
Amides
-
Hoffman Degradation
- What happens to the Carbon Chain in this reaction?
- What does the mechanism include?
- What do you reach with what, to produce what?
Why is this reaction important?
-
Primary amides (amides with only hydrogens on the nitrogen) react in strong, basic solutions of Cl2 or Br2 to form primary amines
- The mechanism includes decarboxylation,
- and thus SHORTENS (!!) the length of the carbon chain
- The mechanism includes decarboxylation,
This reaction is important because it allows you to ADD AN AMIDE TO A TERTIARY CARBON
- Amides
- Physical Properties
- The nitrogen of an amINE is normally sp3 hybridized
- What is the expected hybridization of the nitrogen in an amIDE?
- Physical Properties
-
Because the nitrogen in an amide donates its lone pair via resonance, both the C-O and the C-N bond have double-bond character
- Therefore the hydbridization of the nitrogen will be closer to sp2 than to sp3
- Amides
- Physical Properties
- What does Resonance (aka “Double Bond character”) do to amides?
- Physical Properties
Resonance (Double Bond Character) LIMITS ROTATION:
- The lone pair on the amide nitrogen resonates with the carbonyl double bond
- …giving both the C-O and the C-N bonds double bond character
- This prevents rotation
- …giving both the C-O and the C-N bonds double bond character
- Amides
- Properties
- Would you expect amIDES to be more or less basic than comparable amINES?
- Why?
- Properties
- Nitrogen has less electron density in an amide than it would in a normal amine
- b/c of donation of the lone pair on the nitrogen into the conjugated system
- Therefore, it will be LESS BASIC than comparable amines
- b/c of donation of the lone pair on the nitrogen into the conjugated system
One could also consider the effect of induction
- The carbonyl carbon has a strong partial positive charge
- ….which will withdraw electron density from the amine through the sigma bond
- Amides
- Definition
- Nomenclature
Definition
- An amide is any compound containing a carbonyl with an amine substituent on the carbonyl carbon
Nomenclature
- Named by replacing the “-oic” ending of the corresponding carboxylic acid with “amide”
- i.e., benzoic acid⇒benzamide
- Amines
- Addition of Amines to Carbonyls
- aka, the Formation of ___s and ___s
- Amines add to ___ and ___ to form these ^^^
- aka, the Formation of ___s and ___s
- Describe the 3 steps
- Addition of Amines to Carbonyls
Addition of Amines to Carbonyls….
aka Formation of ENAMINES and IMINES
- Amines add to aldehydes and ketones to form imines and enamines
STEPS:
- The amine acts as a nucleophile
- …attacking the electrophilic carbonyl carbon
- The oxygen is protonated twice
- creating the good LG water
- A base abstracts a hydrogen from the nitrogen and kicks off water in an E2 mechanism
- This forms either an imine or an enamine
- (depending on the substitution pattern of the nitrogen)
- This forms either an imine or an enamine
- Amines
- Addition of Amines to Carbonyls (Formation of Enamines and Imines)
- What do 1°, 2°, and 3° amines yield, respectively?
- Addition of Amines to Carbonyls (Formation of Enamines and Imines)
- Primary (1°) amines:
- yield IMINES
- Secondary (2°) amines:
- yield ENAMINES
- Tertiary (3°) amines
- DO NOT REACT
- Amines
- Definition
- Properties
- Amines can act as either…?
- 1° and 2° amines usually act as?
- 3° amines always act as?
- Why?
- Amines with 4 R groups act as…?
- as long as…?
- Amines are capable of…?
- Amines can act as either…?
Definition:
- An amine is any organic compound that contains a basic nitrogen atom
Properties
-
Amines can act as either bases or nucleophiles
- Primary or secondary amines usually act as nucleophiles
- Tertiary amines ALWAYS act as bases
- (because they are too sterically hindered to act as nucleophiles)
-
Amine Basicity:
- Basicity decreases from tertiary to secondary to primary to ammonia due to the electron donating effects of the R- groups
- Amines attached to aromatic rings are significantly less basic than standard amines
-
Amines with four substituents act as *ELECTROPHILES*
- as long as they have at least one hydrogen
- ex: Ammonium, NH4+
- Amines are capable of *hydrogen bonding*
- Amines
- Gabriel Synthesis
- Describe the steps
- Draw the e- pushing mechanism
- Gabriel Synthesis
STEPS:
- The phthalimide ion (a reactive species with a full negative charge on the nitrogen) acts as a nucleophile
- …attacking the alkyl halide
- via SN2
- …attacking the alkyl halide
- Amines
- Gabriel Synthesis
- = the formation of what from what?
- What does this rxn AVOID?
- Gabriel Synthesis
Formation of a 1° amine from a 1° alkyl halide
- Avoids the side products of alkyl amine synthesis
- Amines
- Properties
- Which functional group forms stronger hydrogen bonds, alcohols or amines?
- Properties
-
ALCOHOLS will form stronger hydrogen bonds
- because there is a greater difference in electronegativity between oxygen and hydrogen than there is between nitrogen and hydrogen
- This greater dipole will create a stronger electrostatic attraction
- …and therefore a stronger hydrogen bond
- Amines
- Nomenclature
- It’s UNIQUE for amines
- Describe the 4 steps for naming amines
- Hint: It does matter whether the amine is primary, secondary, etc.
- Nomenclature
Naming amines is a bit unique, so be sure you understand the system:
- Name the alkane to which the N is attached e.g., propane)
- Add “amine” in place of the “e” on the end of “ane” (e.g., propanamine)
- It is also acceptable to separate the substituent name (e.g., propyl amine)
- If the amine is secondary, the longest chain is included in the name as indicated above
- The other chain is added at the beginning, proceeded by the letter “N-“
- e.g., N-ethylpropanamine
- The other chain is added at the beginning, proceeded by the letter “N-“
- If the amine is tertiary or quaternary, add additional substituents to the front of the name in alphabetical order, all with the prefix N- included
- e.g., N,N-diethylpropanamine, or N-ethyl-Nmethylpropanamine, or N,N-dimethyl-N-ethylpropanamine (ATTACHED)
- Amines
- Reduction Synthesis of Amines
- Describe the reduction of Nitro and Nitrile groups
- What do they both get REDUCED TO?
- What do most O-Chem books focus on these groups being reduced by?
- Reduction Synthesis of Amines
Nitro groups
- can be reduced to the associated primary amine
- via all of the listed reducing agents
- e.g., LiAlH4, NaBH4, and H2/catalyst with pressure
- via all of the listed reducing agents
- Most O-Chem books focus on nitro groups being reduced by:
-
metals in HCl M•HCl
- M=Fe, Zn, Sn
-
metals in HCl M•HCl
Nitrile groups
- can be reduced to the associated primary amine
- via all of the above listed reducing agents
- Most O-Chem books focus on nitriles being reduced by:
- LiAlH4
- Amines
- Reduction Synthesis of Amines
- Describe the reduction of Imine and AmIDE groups
- What are both reduced TO?
- What do most O-chem books focus on these groups being reduced BY?
- Describe the reduction of Imine and AmIDE groups
- Reduction Synthesis of Amines
Hint: Amides can only be reduced with ONE reducing agent….
Imines
- can be reduced to the associated 1° amine
- via all of the above listed reducing agents
- O-Chem books focus on Imines being reduced by:
- BH3
- -:CN or
- H2 / catalyst
Amides
- reduce to the associated 1° amine
- via LiAlH4 ONLY
- Amines
- Tautomerization
- Define
- what is it analogous to?
- Draw
- Define
- Tautomerization
Tautomerization
- An enamine and imine interchange
- via a proton shift
Analogous to the keto-enol tautomerization
- Amines
- Amine Basicity
- Offer a plausible explanation for the decreased basicity of aromatic amines
- Amine Basicity
- Aromatic amines are less basic because they donate their electron pair into the ring
- forming a conjugated system with the ring
- Amines
- Addition of Amines to Carbonyls (Formation of Enamines and Imines)
- Provide a possible explanation for why tertiary amines DO NOT REACT with carbonyls
- Hint: Attempt to draw out a mechanism
- Provide a possible explanation for why tertiary amines DO NOT REACT with carbonyls
- Addition of Amines to Carbonyls (Formation of Enamines and Imines)
- Tertiary amines are not good nucleophiles
- because they are TOO STERICALLY HINDERED
- They are more likely to act as a base
-
Even if they were to attack the carbonyl carbon, this would form:
- an unstable quaternary amine
- with a full positive (+) formal charge
- This would be a better LG than the water formed by protonation of the carbonyl
- …and would therefore be kicked back off anyway
- an unstable quaternary amine
- Amines
- “Reduction Synthesis of Amines”
- …Is the reduction of what 4 groups?
- using common reducing agents, such as? (3)
- …Is the reduction of what 4 groups?
- “Reduction Synthesis of Amines”
- Reduction of:
- AmIDES
- Imines
- Nitriles
- Nitro groups
- using common reducing agents such as:
- LiAlH4
- NaBH4
- H2/catalyst with pressure.
- Amines
- Synthesis of Alkyl Amines
- Describe
- Formula=?
- Describe the 2 Steps
- Remember that this rxn results in many side products
- Why?
- Synthesis of Alkyl Amines
Formation of an alkylamine from an amine and an alkyl halide
NH3 + CH3Br ⇒ NH2CH3 + HBr
STEPS:
- Ammonia acts as a nucleophile, attacking the alkyl halide via SN2
- …and kicking off the halide ion
- The halide ion acts as a base, abstracting a hydrogen
- This quenches the charge on the nitrogen
NOTE:
This reaction results in many side products
- because the resultant amine is still a good nucleophile and can react again
- Amines
- _____synthesis is the most common human-body example of an amine acting as a nucleophile
Protein Synthesis
- the amine acts as a nucleophile
- attacking the carbonyl carbon of another amino acid to form a peptide bond
- Anhydrides
- Properties
- Anhydrides are excellent _____
- Properties
Anhydrides are excellent ELECTROPHILES!
- The two carbonyl carbons are highly reactive to nucleophiles
- because the leaving group is a resonance-stabilized carboxylate ion
- Carboxylic Acids
- Decarboxylation
- Draw a mechanism for the base-catalyzed decarboxylation of a β-keto acid
- Decarboxylation
-
Without a base catalyst, this mechanism can also be visualized as a 6- member, concerted, “ring-like” intramolecular reaction
- ….that does not require protonation of the enolate ion
- Carboxylic Acids
- Describe “Decarboxylation”
- What is lost, what is left behind?
- What does the process usually require?
- Describe “Decarboxylation”
Decarboxylation
- The loss of a CO2 molecule from a beta-keto carboxylic acid
- leaving behind a resonance-stabilized carbanion
- The process usually requires catalysis by a base
- The carboxylate ion usually retakes the hydrogen from the base, forming a keto-enol tautomer
- Carboxylic Acids
- Esterification
- Define
- Formula=?
- What is required 1st in order for this rxn to proceed?
- How can you get higher yields?
- Esterification is how ____s are formed
- Esterification
Reaction of an alcohol with a carboxylic acid to form an ester (ROR)
RCOOH + ROH ⇒ RCOOR + H2O
- The hydroxyl group will never leave without being protonated first
- ….to form the “good leaving group water”
- thus this reaction requires an acid catalyst
- ….to form the “good leaving group water”
- Higher yields can be obtained by reacting an anhydride with an alcohol
This is how triacylglycerols are formed:
- A glycerol undergoes esterification with three fatty acids
- Carboxylic Acids
- Nucleophilic Attack of Carbonyls
- Formula=?
- Nucleophilic Attack of Carbonyls
(ex: __+__⇒__)
RCOOH + H2O ⇒ RCOOH2+ + Nu:- ⇒ RCONu + H2O
- Carboxylic Acids
- Physical Properties
- Surprisingly, short-chain carboxylic acids are also soluble in many relatively non-polar solvents
- Such as chloroform (even though they are clearly polar)
- Provide a possible explanation for this observation
- Surprisingly, short-chain carboxylic acids are also soluble in many relatively non-polar solvents
- Physical Properties
- Theoretically, the carboxylic acid dimer (pictured below) would have no net dipole moment
This explains its solubility in non-polar solvents
- Carboxylic Acids
- Describe the “3 Key Features of Carboxylic Acids”
-
Resonance Stabilization
- The carboxylate ion is uniquely stable due to resonance stabilization
-
Induction
- Alpha substituents can either donate or withdraw from the carboxylate ion
-
increasing or decreasing acidity
- REMEMBER: To predict acidity examine the stability of the conjugate base!
- (A principle applicable to any acid)
- REMEMBER: To predict acidity examine the stability of the conjugate base!
-
increasing or decreasing acidity
- Alpha substituents can either donate or withdraw from the carboxylate ion
-
Hydrogen Bonding
- It is worth mentioning twice; don’t forget that carboxylic acids can not only hydrogen bond, but do it twice—to form dimers