OCHEM common reactions, mechanisms, mechanistic steps, and reagents (Important things I often forget)

Markovnikov's Rule

the intermediate that is going to form is going to be the most stable possible intermediate.

Bases vs. Nucleophiles

we use the word base to indicate a Bronsted Lowry base, we use the word nucleophile to indicate a Lewis base.

Nucleophilicity vs. Basicity

Basicity increases with steric hindrance and nucleophilicity decreases

polar protic vs aprotic

Protic solvents are capable of intermolecular hydrogen bonding bc they contain an O-H or N-H bond. Aprotic solvents only solvate cations well (thus, Sn2 and E2 do not form carbocations).

nonnucleophilic bases

Sterically hindered bases. Ex: tert-butoxide (CH3)3CO^-

What are the two possible mechanisms for Nucleophilic substitution?

1. The mechanism has one step and both bond breaking and making occur at the same time. The rate is second order meaning it is dependent on both starting materials.

2. The mechanism has two steps and bond breaking occurs before bond making and a carbocation is thus formed as an intermediate. The rate is first order meaning it is dependent on only one starting material (RX/alkyl halide).

SN2 reaction mechanism characteristics?

1. 1 step Rate=k[RX][Nu^-]

2. nucleophile always attack's from the back

3. Inversion of configuration (if stereochemistry is involved)

4. Unhindered halides react fastest (methyl>primary>secondary...etc.)

5. Favors polar aprotic solvents (they enhance the reactivity of the nucleophile)

SN1 reaction mechanism characteristics?

1. 2 steps Rate=k[RX]

2. Nucleophile attacks from both the front and backsides of the carbocation intermediate.

3. Both inversion of configuration (front side attack) and retention of configuration (backside attack) occur yielding two racemic enantiomeric products. (if stereochemistry is involved)

4. Sterically hindered halides react fastest (tertiary>secondary, primary/methyl= no RXN)

5. Favors polar protic solvents (stabilizing the carbocation intermediate)

Groups vs. Periods (periodic table)

Groups are vertical and periods are horizontal

dehydrohalgenation

An elimination reaction that removes a hydrogen and a halide (usually E2).

E2 reaction characteristics

- 1 step

- second order, rate = k[HX][Base]

- Favored by strong bases

- More substituted halides are favored

- Requires an anti-coplanar arrangement of H and leaving group.

- Better leaving group = faster reaction

- Favors polar aprotic solvents

E2 reaction mechanism

1. The base OH^- removes a proton from the beta carbon, forming H2O (a by product)

2. the electron pair in the anti-co/periplanar beta C-H bond forms the new pi bond.

3. leaving group Br^- comes off with the electron pair in the C-Br bond.

- All processes occur simultaneously.

E1 mechanism

1. The heterolysis of the C-I bond forms a carbocation (rate determining step).

2. A base (either H2O or I^-) removes a proton from a beta carbon and the electron pair from the C-H bond forms the new pi bond.

- all processes occur on at a time (two step reaction)

E1 reaction characteristics

- first order

- two steps

- more substituted halides react faster

- favored by weaker bases; Ex: H2O and ROH

- a better leaving group makes this reaction faster because the bond to the leaving group is partially broken in the rate-determining step.

- polar protic solvents that solvate the ionic intermediates are needed.

Cl^-

Nucleophile only

Br^-

Nucleophile only

I^-

Nucleophile only

HS^-

Nucleophile only

RS^-

Nucleophile only

H2S

Nucleophile only

RSH

Nucleophile only

H^- (of NaH)

Base only

DBN

Base only

DBU

Base only

HO^-

Strong Nuc/Strong Base

MeO^-

Strong Nuc/Strong Base

EtO^-

Strong Nuc/Strong Base

KOt-Bu

Weak nuc./bulky base

H2O

Weak Nuc/ Weak Base

MeOH

Weak Nuc/ Weak Base

EtOH

Weak Nuc/ Weak Base

Nucleophile only; primary

SN2

Nucleophile only; secondary

SN2 or SN1

Nucleophile only; tertiary

SN1

Base only; primary, secondary, or tertiary

E2

Strong Nuc/ Strong Base; primary

SN2 (major product) E2 (minor product)

Strong Nuc/ Strong Base; secondary

E2 (major product) SN2 (minor product)

Strong Nuc/ Strong Base; tertiary

E2

Weak Nuc/ Weak Base; tertiary

SN1 (generally favored) E1 (favored in elevated temps)

Enantiomers

- stereoisomers that are non-superimposable mirror images.

- opposite configurations at ALL chirality centers

Diastereomers

- stereoisomers that are non-superimposable NON-mirror images.

- opposite configurations at SOME chirality centers

Which of the following reaction quantities will have an effect on reaction rate? Why? K_eq, E_a, ΔH°, ΔG°

E_a, becuase the activation energy is the minimum amount of energy needed for a reaction to take place the lower the activation energy the faster the reaction.

Which of the following alkyl halides would react the fastest with -OH in SN2 reaction? Why?CH3CH2Br, CH3CH2Cl, CH3CH2F, CH3CH2I

CH3CH2I, The order of reactivity of alkyl halides for Sn2 reactions relies on which of the halogen atoms is most weakly bonded to the carbon atom. Due to the fact that as atoms get bigger from F to I, bonds get longer, and weaker. The weaker the bond, the more easily it is broken, the lower the activation energy for the reaction and the faster the rate at which it will occur. The carbon-fluorine bond is perhaps one of the strongest bonds in chemistry, and generally regarded as the strongest in organic chemistry, meaning alkylflourides are very inert (unreactive). This is due to Fluorine's extremely high electronegativity.

Which of the following is most likely to react as a nucleophile rather than a base? KOC(CH3)3, CH3COO^-, DBU, DBN

CH3COO^-

Comparing and Contrasting E1 and SN1

-both unimolecular

-both consist of two steps

-the first step of both reactions is exactly the same (the spontaneous loss of the leaving to give the intermediate carbocation)

-the only thing that differentiates them is how the reagent reacts, it either acts as a base (by gaining a proton) or nucleophile (by donating a lone electron pair)

-In an SN1 reaction, a nucleophile attacks the carbocation, forming a substitution product.

-In an E1 reaction, a base removes a proton, forming a new pi bond.

C6H5

phenyl group

POCl3, pyridine

Is used for the dehydration of alcohols to alkenes. Converts alcohol into a good leaving group, and then proceeds by an E2 mechanism using pyridine as a base. Can also be used to convert amides (RC(=O)NR′R″) to nitriles (R−C≡N).

POCl3, pyridine is similar to what reagents?

LiAlH4 (LAH), LiAlH(Ot-Bu)3

1. BH3 (Borane) 2. NaOH, H2O2 are used for?

The Hydroboration of alkenes (converts alkenes to alcohols) and alkynes (converts alkynes to aldehydes).

BH3 (Borane) is similar too?

B2H6(diborane), BH3+THF, BH3+SMe2, 9-BBN

Hydroboration of alkenes regioselectivity?

For instance, when using BH3, boron (BH2) adds to the less substituted end of the alkene and the H attaches to the more substituted end. The H and BH2 add syn to the double bond (syn-addition).

Reactions of acetylide anions with epoxides characteristics?

- Acetylide anions are strong nucleophiles that open up epoxide rings through backside attack on the less substituted carbon (Sn2 mechanism).

-If both carbons are equally substituted will obtain two enantiomeric products

NaNH2(sodium amide) is used for?

- Very strong base

- useful for the deprotonation of alkynes to make acetylides and also in elimination reactions toward the formation of alkynes from dihalides.

- It can also be used to generate arynes (benzynes) which can undergo nucleophilic attack.

NaNH2 is similar to?

LiNH2, KNH2, and

LD; but less sterically hindered.

The reaction of acetylide anions with alkyl halides? Follows what type of mechanism? Common reagents?

- the reactions follows an Sn2 mechanism

- The reaction works best with CH3X and RCH2X.

Formation of acetylide anions from terminal alkynes? Typical reagents used?

Bases such as NaNH2 and NaH

The reaction of acetylide anions with epoxides? Follows what type of mechanism?

-Sn2

-Opening of the ring occurs from the back side at the less substituted end of the epoxide.

What are some typical bases used for the formation of acetylide anions with terminal alkynes?

NaNH2 and NaH

Hydrohalogenation of Alkynes? Follows what rule? Why?

- Addition of HX (X = Cl, Br, I)

- Markovnikov's rule. H bonds to the less substituted C to form the more table carbocation.

Halogenation of alkynes? What intermediates are formed?

- anti-addition of X2 (syn-addition when only 1 equivalent of X2)

- Bridged Halonium ions are formed as intermediates.

Hydration of alkynes? Follows what rule? Why? What is formed?

- addition of H2O

- Markovnikov's rule is followed. H bonds to the less substituted C to form the more stable carbocation.

- An unstable enol is first formed, which rearranges to a carbonyl group.

Hydroboration-Oxidation of Alkynes? What is formed?

- addition of H2O

- An unstable enol is first formed, which rearranges to a carbonyl group.

Hydrohalogenation of alkenes? Common reagents? # of steps? Intermediates/rearrangements? Follows what rule? Stereochemical preferences?

-Reagents: HCl, HBr, or KI + H3PO4

-Addition

-Carbocation intermediates, rearrangements possible

-Markovnikov addition, H bonds to the less substituted C to form the more stable carbocation.

-No stereochemical preference (syn and anti addition occur)

Hydration of alkenes? # of steps? Intermediates/rearrangements? Follows what rule? Stereochemical preferences? Reagents?

- addition of H2O or ROH

- mechanism has 3 steps

- carbocations are formed as intermediates

- Markovnikov's rule is followed. H bonds to the less substituted C to form the more stable carbocation.

-No stereochemical preference (syn and anti addition occur)

- H2O + H2SO4

- ROH + H2SO4

Halogenation of alkenes? Reagents? Intermediates? Rearrangements? Stereochemical preferences?

- anti addition of X2; X = Cl or Br

-Reagents: Br2, Cl2, or I2 in CH2CL2 or CCl4

-Bromonium or chloronium (bridged Halonium ions) intermediates

- no rearrangements can occur

-Anti addition stereochemical preference

Halohydrin Formation with an alkene starting material? # of steps? Intermediates/rearrangements? Follows what rule? Stereochemical preferences? Reagents?

- addition of OH and X; X = Cl, Br.

- 3 step mechanism.

- Bromonium or chloronium (bridged Halonium ions) intermediates

- No rearrangements can occur.

- Anti-markonikov X bonds to the less substituted C.

- Anti addition occurs.

- NBS in DMSO and H2O adds Br and OH in the same fashion.

Hydroboration-Oxidation of Alkenes? Reagents? # of steps? Follows what rule? Rearrangements/intermediates? Stereochemical preferences?

- reagents: 1. BH3, THF or 9-BBN

2. H2O2, NaOH

- 1 step mechanism

- anti-Markovnikov, the OH bonds to the less substituted C.

- Syn addition of H2O results.

Cl2 (chlorine) is used for? Similar to?

-Chlorine is a very good electrophile. It will react with double and triple bonds, as well as aromatics, enols, and enolates to give chlorinated products. In addition, it will substitute Cl for Halogens when treated with light (free-radical conditions). It also assists with the rearrangement of amides to amines ( the Hoffmann rearrangement)

- NCS, Br2, NBS, I2, NIS

NaH (sodium Hydride)? used for? similar to?

- A strong base and a poor nucleophile (bc H only has one lone pair of e^-)

- It is useful for deprotonating alcohols and alkynes, among others. One advantage of using NaH is that the by-product is H2, a gas that does not further interfere with the reaction.

- similar to LiH, KH

Which of the following ethers cannot be prepared by the Williamson ether synthesis?

tert-Butyl phenyl ether

tert-Butyl methyl ether

Methyl phenyl ether

Isopropyl methyl ether

tert-Butyl phenyl ether

Which of the following reactions will provide the best yield of ether by the Williamson ether synthesis?

Phenol and sodium methoxide

Sodium phenoxide and bromomethane

Bromobenzene and bromomethane

Bromobenzene and sodium methoxide

Sodium phenoxide and bromomethane

Williamson Ether Synthesis

The Williamson ether synthesis is an organic reaction, forming an ether from an organohalide and a deprotonated alcohol (alkoxide). This reaction was developed by Alexander Williamson in 1850. Typically it involves the reaction of an alkoxide ion with a primary alkyl halide via an S N 2 reaction.

H2SO4 (sulfuric acid)? Used for?

- Strong acid, pka -3

- It is useful for elimination since its conjugate base [HSO4^-] is a very poor nucleophile (deprotonates alcohols). It finds use in many other reactions as a general strong acid.

[1] Br2; [2] 2eq. NaNH2

TsOH (tosic acid, or TosOH) is used for?

- strong acid pka -2.8, similar in strength to sulfuric acid.

- The conjugate base is poor nucleophile, which makes it useful for the dehydration of alcohols to alkenes.

- Elimination conversion of alcohols to alkenes

TsCl, pyridine is used for?

- Tosyl chloride will convert alcohols to sulfonates, which are exelent leaving groups in elimination and substitution reactions.

- Converts alcohols to alkyl tosylates.

KOC(CH3)3 or KOt-Bu (potassium t-butoxide)? used for? similar to?

- strong sterically hindered (bulky) base

- Useful in elimination reactions for forming the less substituted "non-Zaitsev/Hofmann" alkene product.

- NaOtBu, LiOtBu, LDA (stronger bulky base)

Br2, H2O is used for?

Convert alkenes to halohydrins

SOCl2, pyridine

Substitutes Cl for OH with inverted configuration. Cl is a good LG.

Anti.

Primary or secondary only.

Under basic conditions, nucleophiles will attack epoxides at?

the least sterically hindered position (least substituted carbon)

Under acidic conditions, nucleophiles will attack epoxides at?

the most sterically hindered position (most substituted carbon)

Which of the statements about the reactions of ethers with strong acids is true?

HCl, HBr, and HI can all be used.

The mechanism of ether cleavage is SN1 and SN2.

The mechanism of ether cleavage is SN1 only.

The mechanism of ether cleavage is SN2 only.

The mechanism of ether cleavage is SN1 and SN2.

If the reaction of an alcohol with PBr3 follows an SN2 mechanism, what is the stereochemistry of the alkyl bromide formed from

(R)−butan−2−ol?

S

Z configuration

the highest priority groups are on the same side of the double bond

E configuration

the highest priority groups are on the opposite side of the double bond

Addition reaction

- A reaction in which a reagent is added to an unsaturated starting material (ring, alkene, alkyne) to make a saturated molecule.

- Reverse/opposite of elimination reactions

H2, Pd/C

- H2 (hydrogen gas) is used for the reduction of alkenes, alkynes, and many other species with multiple bonds, with catalysts such as Pd/C and Pt.

The synthesis of 2,2,3,3,-tetrachloro-6-methylheptane form trans-6-methyl-2-heptene?

The synthesis of 1-butyne from ethyne and ethanol?

Alkyne with H2O, H2SO4, HGSO4 reaction produces?

Alkyne with R2BH, H2O2, OH^- reaction produces?

Reduction

-Adding H's because protons are electron donors

- Breaking pi bonds to saturate a molecule w more protons is reduction.

Oxidation

- Addition of oxygen results in the loss of electrons due to the fact that oxygens are electron with drawing groups.

- releases energy (endothermic)

oxidation state/number

- the number of electrons exchanged between atoms during the formation of a molecule.

- Oxidation state is the number of electrons a particular atom can lose, gain or share with another atom.

Reduction reactions

Addition of H2; gains of electrons

Reduction of alkenes occurs by? Stereochemistry? Common reagents?

- Catalytic hydrogenation (adding H2 by a metal catalyst)

- syn addition of 2 hydrogens

- treating alkene with H2 will saturate all double bonds (pi bonds); only the degree of unsaturation from rings will remain.

- H2, Pd-C (Pt-C, Ni, Ru)

- The more substituted the carbons on the carbon-carbon double bond, the slower the reaction

- trans product is preferred

Reduction of alkynes with (3 ways)? Stereochemistry? Common reagents?

- 2 equiv. or 1 equiv. of H2, Pd-C (Pt-C, Ni, Ru) results in a reduced alkene if 1 equiv. or a reduced alkane if 2 equiv. Syn addition of 2 hydrogens. Can't stop this halfway.

- Lindlar's catalyst (Pd, CaCO3, Pb(OCCH3)2, quinoline); produces an alkene. Only 1 equiv. of H2 is added. Catalyst is deactivated after. Syn addition.

- Reducing metal, Na, NH3 (solvent) results in an E alkene. Anti addition of Hydrogens occurs.

- trans product is preferred for all

saturated molecule vs unsaturated molecule

Lindlar's catalyst

A heterogeneous catalyst for the hydrogenation of alkynes to cis alkenes. In its most common form, it consists of a thin coating of palladium on barium sulfate, with quinoline added to decrease the catalytic activity.

Reduction of alkyl halides occurs through? Common reagents?

- via SN2, thus unhindered alkyl halides are preferred (methyl, primary, secondary)