Chem 215 Reactions

Ketones/Aldehydes -> Alkylated ketone/aldehyde

Conditions: LDA or THF, then alkyl halide, in cold conditions | Mechanism: LDA or THF attacks the less-substituted carbon, creating a carbanion. The carbanion grabs the C with the halogen on it, the halogen leaves | Notes: LDA/THF attacks the less-substituted alpha carbon

Ketones/Aldehydes -> Alkylated ketone/aldehyde

Conditions: t-BuO, then alkyl halide, in warm conditions | Mechanism: Tertbutoxide attacks the more-substituted carbon, creating a carbanion. The carbanion grabs the C with the halogen on it, the halogen leaves. | Notes: tBuO attacks the more-substituted alpha carbon

Ketones/Aldehydes -> Polyhalogenated ketone/aldehyde

Conditions: Any strong base, then a dihalide | Mechanism: Strong base deprotonates one of the alpha Cs. The new carbanion grabs one halogen, the other leaves. Repeat until all Hs have become halogens | Notes: If a chiral center is made, it produces a mixture of enantiomers

Ketones/Aldehydes -> Monohalogenated ketone/aldehyde

Conditions: Any strong acid, then a dihalide | Mechanism: Acid protonates the oxygen. Its conjugate base steals a hydrogen, the new carbanion attacks the halogen and the other leaves. The other halogen will then deprotonate the OH and it becomes a carbonyl again. | Notes: If a chiral center is made, it produces a mixture of enantiomers

Ketones/Aldehydes -> Alcohol with 1-2 R groups and 1-2 Hs

Conditions: 1. LiAlH4 with Et2O or THF / 2. Acid workup | Mechanism: The H-Al bond attacks the carbonyl carbon, and one of the C=O bonds attacks the aluminum. Then, the H-O bond from the acid removes the AlH3 from its temporary spot on the oxygen, and the O-Al bond deprotonates the acid. | Notes: LiAlH4 reduces all carbonyls to [1] level

Ketones/Aldehydes -> Alcohol with 1-2 R groups and 1-2 Hs

Conditions: 1. NaBH4 / 2. MeOH or EtOH | Mechanism: The H-B bond attacks the carbonyl carbon, and one of the C=O bonds attacks the boron. Then, the H-O bond from the acid removes the boron from its temporary spot on the oxygen, and the O-B bond deprotonates the acid. | Notes: NaBH4 can only reduce [2] (2 bonds to electrophilic atoms) carbonyls

Ketones/Aldehydes -> Alcohol with 2-3 R groups and 1-2 Hs

Conditions: 1. Grignard reagent with Et2O or THF / 2. Acid workup | Mechanism: The bond to the Mg attacks the carbonyl carbon. The C=O bond and the lone pair on O attack the Mg. Then, the O-Mg bond deprotonates the acid, and the O-H bond in the acid removes the Mg from the O. | Notes: Mg0 goes "between" the R-X. To make a carbonyl from just a Grignard, add CO2 (s) as the second step. The acid workup must be a separate step.

Ketones/Aldehydes -> Alcohol with 2-3 R groups and 1-2 Hs

Conditions: 1. RLi and a hexane / 2. Acid workup | Mechanism: The bond to the Li attacks the carbonyl carbon. The C=O bond and the lone pair on O attack the Li. Then, the O-Li bond deprotonates the acid, and the O-H bond in the acid removes the Li from the O. | Notes: Li0 goes "between" the R-X. The acid workup must be a separate step.

Ketones/Aldehydes -> Alcohols with 1-2 R groups and the acetyl group.

Conditions: 1. Acetylide anion (deprotonated alkyne) / 2. Acid workup | Mechanism: The carbanion electrons attack the carbonyl carbon and the C-O bond becomes a lone pair on the O. One of the O's lone pairs will then deprotonate the acid. | Notes: This reaction is limited because of the triple bond. Use a Grignard instead.

Ketones/Aldehydes -> Alkene with 3-4 R groups and 0-1Hs

Conditions: Wittig reagent (R)3P=CR2 | Mechanism: The C=O bond attacks the P and the carbanion electrons attack the carbonyl C (this forms a PO box). Then, the C-O bond moves to become a P=O bond, and the P-C bond moves to become a double bond at the alpha carbon. | Notes: Make a Wittig reagent: add triphenyl phosphate to a 1/methyl alkyl halide. Then add nBuLi

Ketones/Aldehydes -> Enolate

Conditions: NaH (or any non-nucleophilic strong base) | Mechanism: The H- electrons deprotonate the alpha carbon, and the H-C bond becomes a lone pair on the carbon. The resonance structure is where the double bond now lies between the alpha carbon and the carbonyl carbon, and the negative charge is on the oxygen.

Alkenes -> Alkyne

Conditions: 1. Strong, bulky base / 2. Acid workup | Mechanism: Base deprotonates one of the carbons, creating a new multiple bond, the halogen leaves. This may repeat if there are multiple halogens. | Notes: Requires an acid workup if terminal. This is just an elimination reaction, and the alkene must have a halogen on it.

Alkenes -> Alkyl halide or alcohol

Conditions: H-X (strong Bronstead Acid) | Mechanism: Hydrogen adds across the double bond. X adds to the carbocation | Notes: Creates all possible configurations at the new stereocenter. X will add to the more-substituted carbocation. Prone to C+ rearrangements

Alkenes -> Alkane

Conditions: H2, along with Pt, Pd, or Ni catalyst | Notes: Syn addition of the hydrogens

Alkenes -> Alcohol (more-substituted)

Conditions: 1. Hg(OAc)2, H2O / 2. BH4 | Mechanism: Hg adds across the double bond, one of the OAc groups leaves. H2O then attacks and the ring opens. With NaBH4, the Hg becomes an H. The H2O deprotonates itself | Notes: Backside attack of the ring, but stereochemistry is scrambled. No C+ rearrangements.

Alkenes -> Halohydrin or a dihalide

Conditions: X2 in CCl4, H2O, or base | Mechanism: X2 adds across double bond, one of the Xs leaves. Then either water adds, the other X adds, or base adds, and the ring opens. | Notes: Backside attack for the second addition. Creates a mixture of enantiomers if chiral center made. Water adds to the more substituted carbon of the ring

Alkenes -> Alcohol (less-substituted)

Conditions: BH3, then H2O2/NaOH and an acid workup | Mechanism: H-BH2 adds across the double bond. The H2O2/NaOH makes the BH2 become an OH group. | Notes: Antimarkovnikov addition, H adds to more-substituted

Alkenes -> Epoxide

Conditions: MCPBA | Mechanism: The O in the OH group adds across the double bond. The currently double-bonded O will deprotonate it. The bond from the ester will go to it as a lone pair, and the double bond moves from the carbonyl to the previous ester | Notes: Double bond stereochem conserved, mixture of enantiomers if make chiral center

Alkenes -> Cyclopropane ring

Conditions: Diazomethane (CH2N2) + heat/light | Mechanism: Heat/light causes N2 to leave. CH2 adds across the double bond. | Notes: Double bond stereochem conserved, mixture of enantiomers if make chiral center

Alkenes -> 1,2 or 1,4 adduct

Conditions: H-X (strong Bronstead Acid) | Mechanism: H adds across a double bond. Resonance/rearrangements occur, then the halogen adds to the carbocation. | Notes: Happens to a conjugated diene

Alkynes -> Geminal dihalide or ketone

Conditions: Excess H-X (strong Bronstead Acid) | Mechanism: Hydrogen adds across the triple bond. X adds to the carbocation. Repeat. | Notes: X adds to the more-substituted carbon (Markovnikov's rule)

Alkynes -> Cis alkene, or an alkane

Conditions: H2, along with Pt, Pd, or Ni catalyst | Notes: Syn addition of hydrogens. For an alkene, use a Lindlar catalyst to stop after the first addition

Alkynes -> Ketone

Conditions: 1. Hg(OAc)2, H2O / 2. BH4 | Mechanism: Hg adds across the double bond, one of the OAc groups leaves. H2O then attacks and the ring opens. With NaBH4, the Hg becomes an H. The H2O deprotonates itself | Notes: Backside attack of the ring, but stereochemistry is scrambled. No C+ rearrangements.

Alkynes -> Cyclopropene ring

Conditions: Diazomethane (CH2N2) + heat/light | Mechanism: Heat/light causes N2 to leave. CH2 adds across the triple bond. | Notes: Double bond stereochem conserved, mixture of enantiomers if make chiral center

Alkynes -> Deprotonated terminal alkyne

Conditions: Strong base, then epoxide, then acid workup | Mechanism: Base deprotonates alkyne, alkyne/grignard reagent attacks the less-substituted side of the epoxide, epoxide opens, then is reprotonated by the strong acid

Alkynes -> Aldehyde

Conditions: 1. HBR2, where R is bulky alkyl group. / 2. H2O2 and NaOH / 3. Acid workup | Mechanism: H-BH2 adds across the double bond. The H2O2/NaOH makes the BH2 become an OH group. | Notes: H adds to the more substituted group: anti-Markovnikov addition

Alkyl Halides -> Ether

Conditions: RONa | Mechanism: Oxygen anion attacks carbon, halogen leaves | Notes: Backside attack of the carbon, can form symmetric and asymmetric ethers

Alcohols -> Ether

Conditions: Two alcohols, H2SO4, and heat | Mechanism: Acid protonates one alcohol, H2O leaves. New carbocation is attacked by the other OH group. CB of acid deprotonates the OH | Notes: Backside attack of the carbon. Forms only symmetric ethers, but the conditions are quite extreme.

Alcohols -> Alkyl halide (good leaving group)

Conditions: PBr3 or PCl3 | Mechanism: O grabs the P, one of the halogens leaves. The whole OHPBr2 leaves, the free Br attacks from the backside | Notes: Backside attack at the carbon with the leaving group

Alcohols -> Alkyl halide (good leaving group)

Conditions: Strong Bronstead acid | Mechanism: Protonate the OH so it can leave as water | Notes: Backside attack of carbon with leaving group. Very extreme conditions only--other FGs will react with the alcohol

Amines -> Alkene

Conditions: CH3I, strong base, heat to promote E2 step | Mechanism: Quaternary ammonium salt synthesis occurs (nitrogen repeatedly grabs the CH3 and the I leaves, until N has four bonds to carbon groups). Then, the base will deprotonate a beta hydrogen, form a double bond, and cause the nitrogen to leave. | Notes: Forms the anti-Zaitsev product, so the least substituted alkene is the most favored

Carboxylic acid -> Methyl ester

Conditions: Diazomethane | Mechanism: CH2 of diazomethane deprotonates the O on carboxylic acid. The new oxyanion then grabs the CH3 group and the N2 group leaves. | Notes: Backside attack of the oxygen

Ketones/Aldehydes -> Cyanohydrin

Conditions: KCN, HCN | Mechanism: The lone pair on cyanide's carbon attacks the carbonyl C, and the C=O bond becomes a lone pair on the O. The lone pair on the O deprotonates H-CN. | Notes: Reversible (can become a carbonyl if deprotonated)

Ketones/Aldehydes -> Imine/Schiff Base (C=N-R)

Conditions: Primary amine (NH2R) HCl catalyst, in a pH of 4-5 (buffered solution) | Mechanism: The lone pair on the nitrogen attacks the carbonyl C, and the C=O bond becomes a lone pair on the O. The lone pair on O deprotonates the H-Cl. A second equivalent of the primary amine deprotonates the amine that is now attached to the carbon, forming a hemiaminal. The lone pairs on the oxygen then deprotonate the conjugate acid of the primary amine. Water leaves, and nitrogen's lone pair swings down to become a double bond. One more equivalent of the primary amine then deprotonates the nitrogen one last time. | Notes: Reversible. Only class A carbonyls.

Ketones/Aldehydes -> Enamine (C-N-R2)

Conditions: Secondary amine (NHR2), HCl catalyst, in a pH of 4-5 (buffered solution) | Mechanism: The lone pair on the nitrogen attacks the carbonyl C, and the C=O bond becomes a lone pair on the O. The lone pair on O deprotonates the H-Cl. A second equivalent of the secondary amine deprotonates the amine that is now attached to the carbon, forming a hemiaminal. The lone pairs on the oxygen then deprotonate the conjugate acid of the secondary amine. Water leaves, and nitrogen's lone pair swings down to become a double bond. One more equivalent of the secondary amine then deprotonates the amine one last time. | Notes: Reversible. Only class A carbonyls

Ketones/Aldehydes -> Amine

Conditions: Secondary amine (NHR2), NaBH3CN or NaBH(OAc)3, and AcOH (pH 4-5) | Mechanism: Not necessary. Iminium cation forms after first step (C=N replaces C=O), then through the previous BH4 mechanism in this section, it becomes an amine

Ketones/Aldehydes -> CH2(R2/RH)

Conditions: 1. NH2NH2 (hydrazine), H+ catalyst (buffered pH 4-5) / 2. NaOH, H2O, and heat. OR NH2NH2, KOH, H20/triethylene glycol, heat | Mechanism: Follows the steps for imine formation using hydrazine. NaOH then deprotonates the N and it gains a negative charge. The resonance structure of this, with N=N and a lone pair on the carbon, will deprotonate water. NaOH will then deprotonate the N again, creating a negative charge. This prompts N2 to leave, leaving a lone pair on the carbon. This lone pair will then deprotonate water to form the product | Notes: Wolff-Kishner Reaction. Must draw resonance structures. The leaving of N2 is IRREVERSIBLE, the rest of the reaction up until that point is reversible.

Ketones/Aldehydes -> Geminal diol (OH-C-OH)

Conditions: H2O w/ H+ catalyst | Mechanism: The lone pair on the oxygen deprotonates the acid. The lone pair on water attacks the carbonyl C, and the C=O bond becomes a lone pair on the O. The conjugate base then deprotonates the water.

Ketones/Aldehydes -> Hemiacetal/acetal (OH-C-OR or OR-C-OR)

Conditions: ROH w/ H+ catalyst | Mechanism: The lone pair on the oxygen deprotonates the acid. The oxygen of ROH then attacks the carbonyl C, and the C=O bond becomes a lone pair on the O. Another equivalent of the ROH then deprotonates the one attached to the carbonyl C, forming a hemiacetal. To continue, the lone pair on the O of OH will deprotonate the conjugate acid of ROH, forming water. Water will leave, and the lone pair on the other oxygen will swing down to become a double bond. Another ROH will then attack the C and the double bond becomes a lone pair. The conjugate base deprotonates the attached ROH. | Notes: For hemiacetal, use 1 equiv. ROH. For acetal, use excess ROH. Reversible

Ketones/Aldehydes -> Cyclic acetates

Conditions: HO-C-C-(C)-OH (ethylene/propylene glycol) w/ H+ catalyst | Mechanism: The lone pair on the oxygen deprotonates the acid. One oxygen of the glycol then attacks the carbonyl C, and the C=O bond becomes a lone pair on the O. The conjugate base deprotonates the O in the glycol. The other OH then deprotonates the acid, then leaves as water. The other OH of the glycol attacks the C, and the C=O bond becomes a lone pair. The conjugate base then deprotonates the final OH | Notes: Reversible

Ketones/Aldehydes -> beta-hydroxy carbonyl

Conditions: NaOH in H2O | Mechanism: The base deprotonates the alpha H, which becomes a lone pair on the carbon. The carbanion then attacks the other carbonyl carbon, and the C=O bond becomes another lone pair on the O. The O- now deprotonates water. | Notes: Base-catalyzed aldol addition

Ketones/Aldehydes -> alpha, beta-unsaturated carbonyl

Conditions: NaOH in heat | Mechanism: The base deprotonates the alpha H, which becomes a lone pair on the carbon. The lone pair then becomes a double bond between the alpha and beta carbons and the OH leaves. | Notes: Base-catalyzed aldol condensation

Ketones/Aldehydes -> beta-hydroxy carbonyl

Conditions: H3O+ in heat | Mechanism: The C=O tautomerizes, and the O is protonated. The lone pair on the O then becomes a new C=O double bond and the C=alpha C double bond attacks the other carbonyl C, and its C=O bond becomes a new lone pair. Water deprotonates the positively charged OH. | Notes: Acid-catalyzed aldol addition

Ketones/Aldehydes -> alpha, beta-unsaturated carbonyl

Conditions: H3O+ | Mechanism: The lone pair on the OH attacks a proton. It then leaves as water. Water then deprotonates the alpha carbon, and the C-H bond becomes a double bond between the alpha and beta carbons. | Notes: Acid-catalyzed aldol condensation

Ketones/Aldehydes -> 1,4 adduct then aldol condensation

Conditions: One a-b unsaturated carbonyl, one regular carbonyl, w/ NaOEt, EtOH in heat | Mechanism: OEt deprotonates the most acidic alpha carbon. That carbon's lone pair attacks the unsaturated beta carbon, its double bond jumps to be between the a-carbonyl carbon, and the C=O double bond becomes a lone pair on the O. The lone pair on the O then resonances to become a double bond and the C-aC double bond deprotonates H-OEt. NaOEt deprotonates the other alpha carbon (on the previously unsaturated carbonyl). That new carbanion attacks another carbonyl C, and its C=O bond becomes a lone pair on the oxygen