Orgo Exam 3 Reactions and Important Materials

Grignard Reagents (Carbon Nucleophiles)

Reaction #1 - _________

• Reduce ketone to OH and insert the carbons (located behind Mg) on the same carbon where the ketone was attached.

C-Mg

Synthesis of Grignard Reagents

• Grignard reagent is characterized by the presence of a ______ bond. Carbon is more electronegative than magnesium, so the carbon atoms withdraws electricity from magnesium via induction. This gives rise to a partial negative charge on the carbon atom.

  • The difference in electronegativity between C and Mg is so large that the bond can be treated as ionic

---

• Mg and ether → synthesizes grignard by placing the Mg “behind” the halogen

Cyanohydrin Formation (Carbon Nucleophiles)

Reaction #2 - ________

• Reduce C=O to OH and insert CN on the same carbon. (May form a chrial center)

Reduction to NH2

Reaction #2a) - _________

• Replace CN with NH2

Reduction to Carboxylic Acid

Reaction #2b) - ______

• Replace CN with carboxylic acid

Wittig Reaction

Reaction #3) - ________

• Extension of carbon chain

• C=C bond formation

• Preparation is in situ (prepared and used immediately)

• Spontaneous reaction, driven by the formation of P=O bond

**Add carbons attached to PPh3 onto double bond (where C=O) → must determine if bond is E/Z

Preparation of Ylid Reagents

Reaction #3a) - ___________

Common Bases: NaH, PhLi, n-BuLi, NaNH2

• R-X must be methyl, primary or secondary does not work with tertiary. (Steric hindrance)

• Z

• E

Reaction #3 - Witting Reaction

• Unstabilized ylids (no resonance) = ___ selective

• Stabilized ylids (resonance) = ____ selective

Baeyer-Villiger Oxidation

Reaction #4) - __________

• Formation of an ester, which is inserted on whichever side of the C=O bond is more likely to migrate

  • mCPBA

  • CF3CO3H

  • H2O2, AcOH

• The group that migrates has the ability to stabilize positive charge during migration

Migratory Aptitude

Reaction #4)

Baeyer-Villiger Oxidation - ____

Protons

Shielding and Deshielding Effect from Hb and Ha

• Protons deshield neighboring _____due to their orientation in the applied magnetic field.

Ratios

Integration _____ of Individual Peaks

• utilizes pascals triangle.

Review

Review

distance

Coupling Constant (J value, Hz)

Coupling constant is the _____ between peaks within a H-NMR signal.

• Coupled protons have the same J value → next to each other

  • “a split b” = “b split a”

Splitting Tree

______ Diagram

• Utilizes pascals triangle and J values, start by splitting with the largest J value.

Simple Spin Multiplicity

When all J values are equal, we observe a ___________.

Complex Spin Multiplicity

When all J values are NOT equal, we observe a___________.

Tri-Substituted Alkene System

System 1: Comlex Spin Multiplicity in ___________

• Geminal

• Cis

• Trans

0-3 Hz (small)

Complex Spin Multiplicity in Tri-Substituted Alkene System

• 2J geminal = _____

6-12 Hz (medium)

Complex Spin Multiplicity in Tri-Substituted Alkene System

• 3J cis = _____

12-18 Hz (large)

Complex Spin Multiplicity in Tri-Substituted Alkene System

• 3J trans = _____

10-16 Hz

~7 Hz

4-10 Hz

0.5-2 Hz

0-1 Hz

6-9 Hz

1-3 Hz

0-1 Hz

*Para protons don’t really couple

Couple

• Acidic protons do not ____ because it hops around

Pratice

Practice

oic acid

Nomenclature of Carboxylic Acids

1) The suffix “______” indicates a carboxyl group.

**The parent chain must contain a carboxylic group as it has the highest priority among functional groups

Carboxylic Acid

Nomenclature of Carboxylic Acids

** A carboxyl group that is conntected to a ring is called “________”

• IUPAC: Methanoic Acid

• Common: Formic Acid

• IUPAC: Ethanoic Acid

• Common: Acetic Acid

IUPAC: Propanoic Acid

Common: Propionic Acid

IUPAC: Butanoic Acid

Common: Butyric Acid

Benzoic Acid

Pyruvic Acid

dioic acid

Nomenclature of Diacids

1) The suffix “______” indicates two carboxyl groups

Oxalic Acid

Malonic Acid

Succinic Acid

Glutaric Acid

Adipic Acid

Trigonal Planar

Physical Properties of Carboxylic Acids

(1) Molecular Geometry: ______

Boiling Point

Physical Properties of Carboxylic Acids

(2) Higher ______ than alcohol due to a higher extent of hydrogen-bonding interactions.

Water

Physical Properties of Carboxylic Acids

(3) Higher _____ in water compared to alcohols and aldehydes

• Water solubuility decreases as the relative size of they hydrophobic protion of the molecule increases (Hydrophobic tail)

Acidic

Physical Properties of Carboxylic Acids

(4) It is the most _____ among functional groups

• It is more acidic due to a resoance stabilized conjugate base.

Acidity

Acidity of Carboxylic Acids

• Inductive substitutents can increase _____, however the effect decreases with distance.

Electron-Withdrawing Groups (EWG’s)

Acidity of Carboxylic Acids

• ______ enhance the acidity of benzoic acid due to that it stabilizes the conjugate base by introducing a positive charge to stabilize the negative charge.

Conjugate Base and Acid (HH eq.)

Ratio of ____________

Henderseon-Hasselbach Equation

Determination of Forms of Pyruvic Acid at Physiological pH

• Utilize the ____ equation to determine which form is most formed at a specific pH.

  • Guesstimate by the number determined by pH-pka and 1:1000 (number of zeros)

Review Preparation of Carboxylic Acids

Review Preparation of Carboxylic Acids

Carboxylation of Grignard Reagents

Reaction #5) - ______________

• Formation of a carboxylic acid using CO2 and a Grignard Reagent

• “R” group of Grignard becomes “left” side of COOH

Protic

Reaction #5) - Carboxylation of Grignard Reagents

• Do not add a “_____” solvent together with Grignard

Hydrolysis of Nitriles

Reaction #6) - ___________

• Formation of a carboxylic Acid from a nitrile

  • “Slice in” carboxylic acid at the carbon of the nitrile

Carboxylic Acid Reduction

Reaction #7) - _________

• Reduction process that reduces BOTH ketones and COOH down to an alcohol

Carboxylic Acid Reduction #2

Reaction #8) - ________

• Reduction process that selectively reduces Carboxylic Acids (slices off C=O)

Fischer Esterification

Reaction #9) - _________

• Forms an Ester “on” the -OH of the carboxylic acid using the “R” of the alcohol utilized.

Conversion to Acid Chloride

Reaction #10)- ____________

• Replace OH with Cl, forming SO2 and HCl

al

Nomenclature of Aldehydes

• The suffix “___” indicates an aldehyde

  • The parent chain must include an aldehydic group (it will be number one in the chain)

Over

Nomenclature of Aldehydes

• Aldehyde has a priority ____ alcohol, alkene, and alkyne.

Carbaldehyde

Nomenclature of Aldehydes

• An aldehydic group adjacent to a ring is called “______”

Benzaldehyde

Formaldehyde

Acetaldehyde

One

Nomenclature of Ketones

• Suffix “_____” indicates a ketone group

Over

Nomenclature of Ketones

• The ketone group has priority ____ alcohol, alkene, and alkyne.

Derivatives

Carboxylic Acid _______

• Acid Chloride

• Acid anhydride

• Ester

• Amide

• Cyanide

Acid Halides

Naming Carboxylic Acid Derivatives

(1) _______: replace “-ic acid” with “-yl halide”

Acid Anhydride

Naming Carboxylic Acid Derivatives

(2) _______: replace “-ic acid” with “-ic anhyride”

• Split anhydride into two carboxylic acids

Ester

Naming Carboxylic Acid Derivatives

(3) _______: replace “-ic acid” with (alcohol + acid) “ate”

Amide

Naming Carboxylic Acid Derivatives

(4) _______: replace “-oic acid” with “-amide”

Nitriles

Naming Carboxylic Acid Derivatives

(5) _______: alkanenitrile

Nucleophilic Acyl Substitution

Reaction #11) - _______

• Leaving group on a carboxylic acid derivative is replaced by a nucleophile.

  • Tetrahedral Intermediate

  • Mechanism pattern depends on strength/reactivity of reagent and derivative. → Derivatives with more stable leaving groups are more reactive

LESS

Reaction #11) - Nucelophilic Acyl Substitution

• The relative reactivity of COOH derivatives is based on the stability of the leaving group and how resonance stabilized the deivative is → if it is resonance stabilized it is _____reactive

Review

Review

Reactive Starting Material + Strong Reagent

Reaction #11)

Pattern #1 - _________

• Nucelophilic Attack → Loss of Leaving Group

  • Nucelophile is strong enough to attack right away

Reactive Starting Material + Weak Reagent

Reaction #11)

Pattern #2 - _________

• Nucelophilic Attack → Loss of Leaving Group → Proton Transfer

  • Deprotonation of Nucelophile is required

Less Reactive Starting Material + Strong Reagent

Reaction #11)

Pattern #3 - _________

• Nucelophilic Attack → Loss of Leaving Group

  • Nucelophile is strong enough to attack right away

Less Reactive Starting Material + Weak Reagent

Reaction #11)

Pattern #4 - _________

• Proton Transfer → Nucelophilic Attack → Proton Transfer (x2) → Loss of Leaving Group → Proton Transfer

  • Reaction is too slow without protonation, reaction is must faster by adding a catalyst

    • Acid catalyst activates starting material so nucelophile can attack

Sufficiently Reactive

Nucelophilic Acyl Substitution

• The core pattern involves nucleophilic attack followed by loss of a leaving group

  • Proton Transfer occurs when

1. The starting material is not ______

2. The intermediate is a strong acid

3. You must convert a poor leaving group to a better leaving group (for loss of leaving group)

Preparation of Acid Chlorides

Reaction #12) - ___________

• Replace OH with Cl

Hydrolysis of Acid Chlorides

Reactions of Acid Chlorides

Reaction #13) - ________ (Weak Nucelophile)

• Replace Cl with OH

Alcoholysis of Acid Chlorides

Reactions of Acid Chlorides

Reaction #14) - ________ (Weak Nucelophile)

• Replace Cl with alcohol (ROH minus the H)

Aminolysis of Acid Chloride

Reactions of Acid Chlorides

Reaction #15) - ________ (Weak Nucelophile)

• Replace Cl with Nitrogen group minus one hydrogen

Reduction of Acid Chloride

Reactions of Acid Chlorides

Reaction #16) - ________

• xs LiAlH4 reduces all the way to alcohol

• LiAl(O-t-Bu)3H is sterically hindered so it only reduces down to an aldehyde.

Reaction with Organometallic Reagents

Reactions of Acid Chlorides

Reaction #17) - ________

• xs RMgBr = adds 2 “R’s” to carbon and reduces C=O to an alcohol

• R2CuLi = adds 1 “R” to carbon (replaces Cl) does not reduce C=O to alcohol