Chem 2380 Final Exam Reagents/Reactions

S_N2 Reaction

Need a nucelophile and a good leaving group. Concerted mechanism. Mechanism is required

S_N1 Reaction

Need a leaving group and a nucelophile. Forms a carbocation. Which will move to the more substituted carbon. Stepwise mechanism.

E1 Reaction

Does not require strong base, carbocation rearrangement is possible for a more stable carbocation.

E2 Reaction

Requires a strong base, C—H bond must be 180 degrees to the C-LG bond.

Addition Reaction

Reactions of alkene. It is protonated by a strong acid. Forms a carbocation intermediate.

Catalytic Hydrogenation in the presence of a ketone/aldehyde

A reducing agent. H₂ and a metal such as Pt, Pd, or Ni.

Sodium Borohydride in the presence of a ketone/aldehyde

A reducing agent. NaBH₄ in a EtOH, MeOH, or H₂O (protic solvent)

Lithium Aluminum Hydride (LAH) in the presence of a ketone/aldehyde

A reducing agent. LiAlH₄ in a protic solvent (often water). Far more reactive than NaBH₄

Chromic acid in the presence of a primary alcohol.

Oxidizing agent, CrO₃ or Na₂Cr₂O₇ in aqeuous acid. Will oxidize a primary alcohol to a carboxyilic acid.

PCC in presence of a primary alcohol

Oxidizing agent. PCC or pyridinium cholorochromate used to produce an aldehyde.

PCC or Chromic acid in presence of secondary alcohol

Oxidizing agent. Will convert any secondary alcohol into a ketone.

Swern Oxidation

Oxidation of primary alcohols to aldehydes and secondary alcohols to ketones. Using DMSO (dimethyl sulfoxide) and oxalyl chloride to form active oxidant. Et₃N facilitates elimination to form pi bond. Mechanism is required.

Dess-Martin Oxidation

Oxidizing reagent. DMP (Dess-Martin Periodane) oxidizes primary alcohols to aldehydes and secondary alcohols to ketones.

Grignard Reagent in the presence of a ketone/aldehyde.

Strong base and nucleophile. RMgX. Have to use aprotic solvents or protecting groups such as TMS.

Preparation of conjugated diene via elimination

Using a sterically hindered strong base.

Electrophilic Addition to conjugated dienes

Adding X₂ to a conjugated system resultings in the 1,2- and 1,4- addition products.

Diels-Alder Reaction

A conjugated system with an alkene form a cyclic or bicyclic system with a single pi bond or dimer. Dieneophile must posess an electron withdrawing group such as an R, OR, OH, or CN group. Diene must be in the s-cis conformation.

Permanganate in the presence benzylic positions

An oxidation reagent. KMnO₄ with water and heat. Produces the deprotonated benzylic acid, add H₃O⁺ to produce benzylic acid.

Free Radical Bromination

Benzylic positions can readily undergo free radical bromination using NBS and peroxides (ROOR)

Alkenes in benzylic positions

Using H₂ and Pt at 2 atm alkenes can be selectively hydrogenated in the presence of a benzene ring.

Reduction of Benzene

Using excess H₂ and Ni at 100 atom. Benzene can be reduced to cyclohexane.

Electrophilic Aromatic Subsitution - Halogenation

Using X₂ and a metal catalyst such as FeCl₃/FeBr₃/AlBr₃. Mechanism required.

Electrophilic Aromatic Subsitution - Sulfonation

Using SO₃ as the electrophile and H₂SO₄ as the catalyst. This whole reaction is equilibria.

Electrophilic Aromatic Subsitution - Nitration

Using HNO₃ and H₂SO₄ as the acid catalyst.

Formation of Aniline from Nitration

Using Fe or Zn, along with HCL and a strong base, usally NaOH forms Aniline a type of amine.

Benzene to Aniline

1. HNO₃/ H₂SO₄

2. Fe or Zn, HCl

3. NaOH

Friedel-Crafts Akylation

Using an akyl halide and AlCl₃ as the acid catalyst produces a benzene with an akyl group. The carbocation acts as the electrophile. This reaction can also be done using a terminal alkene and H⁺ (a tertiary carbocation) or using cyclohexanol and BF₃ where the OH-BF₃ will act as a LG and form a secondary carbocation.

Friedel-Crafts Acylation

Using an acyl halogen (usually Cl) and AlCl₃ to produce a aromatic ketone or acylbenzene.

The Clemmensen Reduction

From an acylbenzene it can be reduced using Zn/Hg with HCl (reflux). Similar to Wolff-Kishner.

Nucleophilic Aromatic Substitution (S_NAr)

A strong nucleophile attacks an electron poor benzene. The ring must possess a strong EWG and a good leaving group. This LG must be ortho/para to EWG.

Elimination-Addition / Formation of Benzyne intermediate

Using NaNH₂, NH₃(l) and H₃O⁺ in the presence of an chlorobenzene or another halobenzene. Produces it into Aniline. This forms the benzyne intermediate.

Ozonolysis of Alkenes

This will cleave a C=C double bond. This can form two aldehydes, two ketones, or one of each.

Acid-Catalyzed Hydration

In the presence of a terminal alkyne using H₂SO₄, H₂O and HgSO₄ this can produce a methyl ketone after tautomerization.

Reduction of Ester/Aldehydes and Acyl Chlorides

Using LAH or LiAlH₄ on any of the above forms a primary alcohol.

Lithium Aluminum Hydride (LAH) in the presence of an acyl chloride

LAH with (O^tBu)₃ in cold temps will form an aldehyde. This will also work on acylbenzenes,

DIBAL-H in the presence of esters and nitriles

Using DIBAL-H in hexanes, then adding water will form aldehydes. In a cyclic ester this will produce an aldehyde and an alcohol.

Carboxyilic Acid to Aldehyde

Using SOCl₂ to form an acyl chloride then using LAH in Et₂O and water to form aldehyde.

Acetals - Aldehydes

In the presence of an aldehyde using excess strong base, and strong acid will form an acetal and water. The acetal is favored at equilibrium.

Acetals - Ketones

In the presence of a ketone using excess strong base, and strong acid will form an acetal and water. The acetal is NOT favored at equilibrium.

Hydrolysis of Acetals

Under acidic conditions acetals will react with water to reform the corresponding ketone/aldehyde. Acetals are stable under basic conditions and will not react.

Diol in the presence of ketones

Excess diol and strong acid will turn the ketone into a cyclic acetal. This is reversible under acidic conditions.

Cylic and non-cyclic thioacetals

Ketones/aldehydes in the presence of sulfur nueclophiles will form thioacetals and thiols will form cyclic thioacetals.

Alkanes in the presence of thioacetals

Thioacetals can be converted into alkanes when Raney nickel is present. Good for reducing ketones/aldehyde to the corresponding alkane.

Primary amines in the presence of aldehydes/ketones

When primary amines are in the presence of a ketone/aldehyde with strong acid, it will form an imine and water. Almost identical to enamine formation.

Secondary amines in the presence of aldehydes/ketones

When secondary amines are in the presence of aldehydes/ketones with catalytic acid it will form an enamine and water. Almost identical to imine formation.

Wolff-Kishner Reduction

A two-step synthesis converting a ketone to an alkane. Using H₂N—NH₂ (strong acid) and dehydration. Then using a strong base/ water and heat. Similar to Clemmensen Reduction.

Hydrolysis of Imines and Enamines

Using water and strong acid, imines and enamines will oxidize back to a ketone and the respective electrophile.

Cyanohydric Acid in the presence of ketones/aldehydes

Using HCN or cyanohydric acid on a ketone or aldehyde will result in cyanohydrin formation. This reaction works better under basic conditions so KCN is often used alongside HCN. Chirality is possible.

Wittg Reaction

From a ketone or aldehyde using a yilde will result in a new C=C double bond.

Horner-Wadsworth-Emmons (HWE) reaction

Using a reagent similar to Wittig. It is a resonance stabilitized carbanion. Made by a phosphonate ester and NaH. Used to create a C=C double bond from a ketone or aldehyde.

Baeyer-Villiger Oxidation

An aldehyde or ketone is converted to a carboxyilic acid acid or ester respectively. Using a peroxy acid R-COOOH / MCPBA meta-Chloroperoxybenzoic acid

Primary Alkyl Halide to Carboxyilic acid

Using 1. HCN 2. H⁺ with water and heat carboxyilic acid can be synthesized.

Synthesis of Acyl Chlorides from Carboxyilic Acids

Using SOCl₂ (COCl)₂ or PCl₃/PCl₅

From Acyl Chloride to Carboxyilic acid

Using water and a strong base like KOH an acyl chloride can be made into a carboxyilic acid.

Acyl Chloride to Ester

Using R’OH and pyridine on an acyl chloride will produce an ester

Acyl Chloride to Amide

Using R’NH₂ on an acyl chloride will synthesize an ester

Acyl Chloride to an Acid Anhydride

Using a RCOOH base on an acyl chloride will synthesize an acid anhydride

Fischer Esterification

From a carboxyilic acid using MeOH (methanol) and strong acid creates an equilibria to an ester and water. The reverse of this would be hydrolysis under acidic conditions and will use the ester to produce carb. acid and methanol.

Saponification

The hydrolysis of esters under basic conditions. an acid work-up is necessary to obtain the neutral carboxylic acid product. From an ester using a strong base such as NaOH then using H₃O⁺ will synthesize the corresponding carboxylic acid and alcohol.

Lactone

When an alcohol and carb. acid are on the same molecule they can intramolecularly react to form a lactone.

Amides from Carb. Anhydrides

Using exccess secondary amine on a carb. anhydride will produce a amide and a carboxylate salt.

Amides from Esters

From an ester combined with secondary amine can produce an amide with the corresponding alcohol

Acid/Base Hydrolysis with Amide

An amide when combined with strong acid/base with heat and water will produce a carb. acid or a carboxylate ion with ammonium or ammonia respectively.

Amide into Nitrile

Using P₄O₁₀ you can dehyrdate the amide and turn it into a nitrile. This photo also shows the chemical pathway from a alkyl halide to a nitrile.

Hydrolysis of a nitrile

Adding a strong acid or base with water and heat.

Acidic Tautomerization

By adding a strong acid to a ketone it tautomerizes into an enol

Basic Tautomerization

By adding a strong base a ketone will tautomerize into an enol

Lithium diisopropylamide for the formation of Enolates

LDA is a strong base but a very weak nucleophile and is used to remove the less hindered alpha hydrogen to form an enolate. if an aldehyde is added to an enolate a directed aldol addtion occurs.

Alpha-Halogenation Acidic conditions

Using a strong acid ketones/aldehydes can undergo alpha halogenation with a diatomic halogen gas

Alpha-Halogenation Basic Conditions

Under basic conditions a ketone/aldehyde will under go alpha-halogenation. This typically results in poly-halogenation and multiple of the same halogen will be added to the same carbon.

Haloform Reaction

Under basic conditions methyl ketones are converted to carb. acids using excess halogen and hydroxide

Hell-Volhard-Zelinski Reaction

Excess halogen gas and phosphorus with water in the presence of a carb acid will perform alpha halogenation

Alpha-substitution of esters

Using LDA, THF and a R-X group will substitute the alpha hydrogen for the R group.

Synthesis of dialkylacetic acid

Using a strong base and a alkyl halide the alpha hydrogen is replaced with the R group. Using a tert-butyl base and another R-X group to poly akylate the middle cardbob then applying heat to separate the two ketones.

Synthesis with Acetoacetate

Similar to the Synthesis of dialkylacetic acid, the synthesis with acetoacetate uses strong bases and akyl halide groups to add R groups to connected ketones.

Aldol Additions

If an enolate attacks an aldehyde an aldol addition reaction occurs. Using a strong base and a water solvent. The reverse is the retro-aldol reaction.

Aldol Condensations

When an aldol is heated or placed under basic/acidic conditions an unsaturated carbonyl forms.

Intramoleculelar Aldol Reactions

If both an aldehyde or ketone are present on a long enough carbon chain, along with a strong base. They can undergo an intramolecular aldol reaction and form a cyclic compound with a C=C double bond.

Claisen Condensations

Esters when combined witha strong base and water will form a beta-keto ester. Dieckmann cyclization are intramolecular claisen condensations.

Conjugate Addition

strong nucleophiles will tend towards 1,2 whereas weaker nucelophiles will add towards 1.4

Stork-Enamine Synthesis

This takes a ketone and uses an aniline to form an enamine.

Robinson Annulation

Two steps:

1. Michael addition (with a strong base)

2. Intramolecular aldol condensation

Amine from Carboxyilic acid

SOCl₂ with excess NH₃ will create an amide. This can then be made into an amine using LAH and water.

Azide Synthesis

Conversion fo an akyl halide to an azide via S_n2 by a nucelophile like NaN₃ then using a strong base or LAH to conver the N₃ to an NH₂

Gabriel Synthesis

Synthesis of primary and secondary amines from phthalimide. Using strong base and alkyl halide. Then using hydrazine (NH₂NH₂) and a strong base to produce a primary amine.

Reductive Amination

Ketone or aldehyde is converted into an imine, then into an amine using a primary amine, dehydration and water.

Sodium Cyanoborohydride

Similar to NaBH₄. Must be formed in situ to yeild the desired amine.

Diazotization

primary amine with NaNO₂ will yield a diazonium salt. This can then be used for Sandmeyer reactions.

Carbon Dioxide in the presence of Grignard reagent

Using R-MgX and a strong acid. Carb. acid can be synthesized.