CHE 3332: Organic Chemistry II Week of September 6th, 2021

Hey guys! I am Megan Hudson- the new master tutor for CHE 3332 this Fall 2021 semester. I am a Senior Biology major with a concentration in Global Health on the pre-med track. I will be making a resource every week that aims to summarize the content covered in both o-chem II sections. In-person group tutoring sessions will take place every Thursday from 5:15 - 6:15 pm in Sid Rich Rm. 75! In these sessions I will provide practice problems and be available for specific questions. To reserve a spot, go to https://baylor.edu/tutoring. I hope to see you there!

TOPIC OF THE WEEK: Both Dr. Hodson and Dr. Zinke's sections seem to be covering CH. 13: Alcohols and Phenols and CH. 14: Ethers and Epoxides; Thiols and Sulfides Key Words: Alcohols, Phenols, ARIO, Ethers, Sulfides, Epoxides, Ring opening Review of Alcohol Properties and Nomenclature: https://www.youtube.com/watch?v=TXJ0ffXyLq0 For more review videos, I recommend checking out Leah4Sci's website: https://leah4sci.com/organic-chemistry-basics/alcohol-reactions-in-organic-chemistry/

HIGHLIGHT #1: ALCOHOLS What is an Alcohol? Compounds containing a hydroxyl (-OH) functional group that is directly bound to a sp3 carbon. Look for an -ol ending when naming! Alcohols can be primary, secondary, or tertiary or can be attached to an aromatic ring to make a phenol. This plus ARIO (Atom, Resonance, Induction, and Orbital) will help you determine the stability of the alcohol! Reactions involving Alcohols: Forming an Alkoxide/ Phenolate by deprotonating the alcohol: a. Strong Base can be used to deprotonate the alcohol b. Consider ARIO to determine if deprotonated ion will be favorable

Review of Old Reactions involving Alcohols: Reaction Type Substrate Reagents Products SN1 Tertiary Alkyl Halide H2O or other weak

nucleophile Tertiary Alcohol

SN2 Primary Alkyl Halide NaOH or other strong nucleophile

Primary Alcohol

Acid- catalyzed hydration

Alkene Dilute H2SO4 Mark Addition- OH on more substituted carbon

Oxymercuration-demurcuration

Alkene 1. Hg(OAc)2, H2O 2. NaBH4

Mark Addition- OH on more substituted carbon

Hydroboration-oxidation

Alkene 1. BH3 x THF 2. H2O2, NaOH

Anti-Mark Addition- OH on least substituted carbon

Addition: Dihydroxylation

Alkene EITHER OsO4, H2O2 OR KMnO4, OH-, cold, dilute

Syn Addition of 2 OH groups on either side of the double bond

Addition of Acetylides to Carbonyl Compounds

Carbonyl Group + Alkyne Ion

1. THF 2. H3O+

sp3 carbon attached to OH group, original carbonyl R groups and carbon triple bond

SN2 Substitution Primary or Secondary Alcohol

Hydrogen Halide (H-X)

Primary or Secondary Alkyl Halide

SN1 Substitution Tertiary Alcohol Hydrogen Halide (H-X)

Tertiary Alkyl Halide

Reduction of a Carbonyl Group to make an alcohol: 3 Different Reagent Options: 1. H2 with a metal catalyst 2. NaBH4 3. Lithium aluminum hydride (LAH) How do you decide which reagent to use? H2

requires a metal catalyst and high temperature and pressure conditions, and NaBH4 is a weaker reducing agent than LAH. All methods can be employed with ketones and aldehydes, but LAH should always be employed when the reagent is an Ester. A Grignard reagent can also be used to transform a carbonyl group (aldehyde or ketone) into an alcohol Protection of alcohols: Trimethylsilyl ether (TMSCl) can be used to react/ protect an alcohol while you perform a separate Grignard reaction. If a protecting group is not used, the

Grignard with react with any carbanion in the mixture and quench it. Use H3O+ or TBAF to deprotect the alcohol.

HIGHLIGHT #2: ETHERS What is an Ether? It's an oxygen atom bound to 2 carbon groups. Be sure to keep this straight from an Ester (RCOOR). Reactions with Ethers: Reaction Type Substrate Reagents Products Williamson Ether Synthesis

Primary, Secondary or Tertiary Alcohol

1. NaH 2. RX

Ether with alcohol replaced with R group

Alkoxymercuration demurcuration

Alkene 1. Hg(OAc)2, ROH 2. NaBH4

Mark Addition- Ether on more substituted carbon

Alcohol dehydration 2 Alcohols H2SO4, heat Symmetrical ether Acidic Cleavage of an Ether

Ether Hydrogen Halide (H-X)

2 Alkyl Halides

HIGHLIGHT #3: EPOXIDES

What is an Epoxide? It's a cyclic ether that contains an oxygen within a closed ring Reactions with Epoxides Reaction Type Substrate Reagents Products Preparation with PeroxyAcids

Alkene MCPBA or MMPP If Alkene was cis, epoxide's substituents are cis If Alkene was trans, epoxide's substituents are trans

Base promoted cyclization of halohydrin

Alkene 1. Cl2, H2O 2. NaOH

Halide and OH middle transition state is trans, ends with Cis epoxide

Sharpless asymmetric epoxidation (SAE)

Alkene R3COOH, Ti (O-butyl)4, and (+)- DET OR (-)- DET

Single enantiomer: positive version creates the epoxide from the top face and the negative version creates the epoxide from the bottom face

Ring opening reactions of epoxides

Reaction Type Substrate Reagents Products Acid catalyzed Epoxide H3O+ Nucleophile will

attack tertiary carbon > primary > secondary and OH will be trans to Nucleophile group

Base catalyzed Epoxide OH- Nucleophile attacks less substituted carbon and forms trans diol

Grignard’s Epoxide 1. XMgBr 2. H2O/ H+

Grignard attacks at lease substituted carbon

HIGHLIGHT #4: SULFIDES

What is a sulfide? It's an ether with a S substituted for O (thioether) What is a thiol? It is the sulfur equivalent of an alcohol Reactions with Sulfides Reaction Type Substrate Reagents Products Thioether synthesis Thiol 1. NaOH

2. Alkyl halide Thioether

Thiol (Mercaptans) oxidized to disulfide

Thiol NaOH/H2O Br2

Disulfide

Disulfide reduced to thiol

Disulfide HCl, Zn Thiol

TEST YOURSELF: SYNTHESIS

THINGS YOU MAY STRUGGLE WITH: 1. Remember reduction is gain of electrons and oxidation is loss of electrons (OIL RIG). Try to determine whether molecules are being reduced or oxidized either from the reagents or from the final product. Use this to gauge what specific atoms you will be working with and whether you might need to employ a protecting group, etc. 2. Organic Chemistry 2 expects you to understand chirality and be able to visualize what the molecules look like in space. To do this, draw out all electrons, arrow-pushing, and dashes and wedges to ensure success in a problem. 3. It is easy to confuse the reagents and it is challenging to remember exactly what they do to the substrate, so I recommend doing lots of practice problems and making an ongoing chart that lists what the reagent does, like I have done above for these chapters. This can be referred to when you get stuck on synthesis problems. Answers for Synthesis Problems:

All diagrams, tables, and external information is property of Organic Chemistry by David Klein, unless

otherwise specified.