UW Chem 238 Final

Alcohol to alkene

1. TsCl

2. Base

Alcohol to alkene (another way)

H2SO4 (H+)

(or H3PO4, or other strong acids)

Alcohol to alcohol (inverted)

1. TsCl

2. NaOH

Alcohol to ether

1. TsCl

2. NaOR

Alcohol to ether (another way)

1. Na(H)

2. RBr (R-X)

1° Alcohol to carboxylic acid

H2CrO4 (or K2Cr2O7)

1° Alcohol to aldehyde

PCC

2° Alcohol to ketone

H2CrO4 or PCC

1° or 2° Alcohol to 1° or 2° R-Cl

SOCl2

1° to 2° Alcohol to 1° or 2° R-Br

Ph3PBr2

Alcohol to alkoxide

NaH + R-OH

Alcohol to alkoxide (another way)

2RO-H + 2Na

(1°, 2°, or 3°) Alcohol to (1°, 2°, or 3°) R-X

H-X (and protic solvent)

Alcohol to R-Nuc

1. TsCl

2. Nu:- (i.e. Br-, I-, Cl-, CN-, N3-)

Thiol to disulfide

[O] (air or I2)

Thiol to sulfonic acid (R-SO3H)

HNO3 or KMnO4 (strong oxidants)

Ether to alcohol (and R-X)

H-X (I > Br > Cl, increasing reactivity as acid gets stronger)

Epoxide to alkyl chain with -OH and Nu (OH-R-O-Nu) showing SN2 mechanism

Nu:- (i.e. OH-, RO-, organolithium reagents) and (related (?)) protic solvent (EtOH, H2O) ??

Epoxide to alkyl chain with -OH and Nu (OH-R-O-Nu) showing SN1 mechanism

Nu:- (i.e. OH-, RO-, organolithium reagents) and H+ (acid) ??

Alkene to epoxide

mCPBA

Halohydrine w/ X and OH dihedral 180° from each other to epoxide

NaOH

Achiral alkene to chiral epoxide (enantiomer)

Ligand (chiral catalyst), Ti(OiPr4), and tBuO-O-H)

Alkoxide to ether (Williamson Ether Synthesis)

1° or 2° Alkyl Halide

Alkene to ether

1. Hg(OAC)2

2. Alkyl alcohol (R-OH)

3. NaBH4

1°, 2°, or 3° alcohol to ether (and water byproduct)

H+ (and another R-OH)

Alkene to ether

H+ and R-OH

Alkene to three membered carbon ring

Carbene

Alkene to alcohol (Anti-Markovnikov)

1. BH3

2. H2O2

Alkene to alcohol (Markovnikov)

1. Hg(OAc)2

2. H2O

3. NaBH4

Alkene to 2 ketones

O3 (ozonolysis)

Alkene to vicinal dihalide

Br2 (X2)

(Unsubsituted) epoxide to alcohol (R-OH)

1. R-MgX

2. H+

Epoxide to alcohol with neighboring -R addition

R2Cu(CN)Li2

Alkene to syn glycol

OsO4, R3N+-O- (Amine oxide), and H2O

Alkene to anti glycol

mCPBA and H+

Glycol to two carbonyl (C=O) products

H5IO6

Ether (ROR) to oxonium salt (R3O+) or sulfide (OSO) to sulfonium salt (R3S+)

R+BH4- or R+NO3- or R+ClO4- (a lot of EN atoms sharing one charge)

Conjugated diene + HBr

1,2-addition/1,4-addition

Diene to alkene with X substituted on allylic carbon

H-X

Benzene to brombenzene (bromination)

Br2 and FeBr3

Benzene to nitrobenzene (nitration)

HNO3 and H2SO4

Benezene to benzene sulfonic acid (sulfonation)

SO3

Benzene to Ar-R (alkyl benzene)

R-Cl (3° R-X best due to c/c stability and no subsequent rearrangement) and AlCl3

Alkyne to with X (halogen) substituted alkene (Markovnikov)

2HX

Alkyne to alkene (E/Trans)

Na and NH3 (Dissolved Metal Reduction)

Alkyne to alkene (Z/Cis)

H2 and Lindlar's Catalyst

Alkyne to Alkane (Z/Cis/Syn)

H2 and Cat (=Ni, Pd, Rh, or Pt) (Hydrogenation)

Alkyne (to an enol) to a carbonyl

1. Hg(II) (i.e. HgSO4 or Hg(OAc)2)

2. H2O

3. H2SO4 (H+/acid)

*(Markovnikov hydration of Alkynes)

Alkyne (to an enol) to a carbonyl

1. (>—<)2BH

2. H2O2/OH- (Base)

(Anti-Markovnikov hydration)

Alkene with alcohol to diene (E1)

H+ (acidic conditions)

Alkene with halide to diene (E2)

B:- (basic conditions)

Ar + E-Y (—> sigma complex) —> Ar-E + HY

Electrophilic Aromatic Substitution (EAS) ... (unlike alkenes, which would undergo addition in the presence of electrophiles)

Geminal or vicinal dihalide (to alkene to acetylide) to alkyne

1. 3NaNH2 and NH3

2. H2O (aqueous work-up)

Diene + dienophile + heat

Cyclohexene (Diel-Alder Reaction)

*Pericylcic reaction

*EWG on dienophile = faster

*EDG on diene = faster

*Diene must be in s-cis conformation

*Stereochemistry preserved

*Endo (diene on top, dienophile on bottom/closer to pi-bond of diene) and exo (dienophile on top, diene on bottom/further to pi-bond of diene)

X-Acetyl (acyl halide) + Ar + AlCl3

Ar-Acetyl (and AlCl3-(Ar-Acetyl) complex and HCl)

Carboxylic acid to acyl halide

SOCl2

Ketone to 2° alcohol

NaBH4 and H+(or water)

Aldehyde to 1° alcohol

NaBH4 and H+(or water)

Acyl chloride to 1° alcohol

NaBH4 and H+(or water)

Carboxylic acid to 1° alcohol

LiAlH4 and H+(or water)

Friedel-Crafts Acylation (Hydroacylation) product (Benzene with acyl group added (Ar-C(=O)R) to benzene with alkyl chain (Ar-C-R) in acidic conditions

Zn(Hg) and HCl (Clemmesen Reduction)

Friedel-Crafts Acylation (Hydroacylation) product (Benzene with acyl group added (Ar-C(=O)R) to benzene with alkyl chain (Ar-C-R) in basic conditions

H2N4 and KOH (Wolff-Kirschner Reduction)

How to get a NH2 group added onto a benzene ring

1. HNO3/H2SO4 (Nitration)

2. Zn(Hg)/HCl (**Cannot use H2N4/KOH)

Tells us where positive charge is in allylcation

LUMO

Tells us where negative charge is in allylanion

HOMO

Tells us where radical (unpaired) electron is in radical allyl

SOMO

Allylic halogen to allylic alcohol(s) (more stable cation yields major product due to allylic rearrangement)

H2O (and Base, like Na2CO3)

Allylic halogen to allylic ether(s)

R-ONa

Allyl to Allylic Br

NBS and heat

Allyl to Allylic Cl

Cl2 and heat (500°C)

"Natural Products"

2° Metabolites (molecules not essential to life but are made by organisms as low investment weapons)

Polyketides

Carbon based, Oxygen substituents, methyl/ethyl substituents

*(Made from stuff that is made from the Krebs Cycle)

* Often used by us as starting point to make Rx drugs or used as the drug themselves

Alkaloids

(Very often) polycyclic and contain N (often more than one N), because derived from amino acids

*(Again) Usually made my bacteria and plants

Terpenes

All derived from two precursor molecules: isopentyl diphosphate and dimethylallyl diphosphate

*Both of these precursor molecules are derived from acetate

*Many combinations, efficient way to build

(3) Largest classes of 2° metabolites

Terpenes, Polyketides, and Alkaloids (derived from amino acids)

Leaving group that leads to Terpene formation and what kind of mechanism it undergoes

OPP and SN1

Forming terpene

1. Make long chain (using enzymes (?))

2. Cyclize (using enzymes (?))

3. Oxidize (using enzymes like P450)

Steroids

A class of compounds

Derived from terpenes

Share a common tetracyclic core

Notable/common example: Cholesterol

What do statins do?

Control the entry point into the synthesis of cholesterol (inhibitor)

LDL

Takes cholesterol from liver to tissue

HDL

Takes cholesterol from tissue to liver

Phenol to phenyl alkoxide

NaOH

Nucleophilic aromatic substitution (NAS)

Aromatic with EWG and LG to aromatic with EWG and Nu

*Addition followed by elimination

*Requires LG ortho or para to EWG

*EWG can be resonance (NO2, CN, or acyl) or heteroatom in ring (like N)

*More EWG groups = faster reaction

*Needs strong nucleophile

*LG activity = F>Br>Cl>I --> LG ability to leave doesn't affect overall rate of reaction

Phenol (to alkoxide) to phenol with carboxylic acid (salicylic acid) (Kolbe Reaction)

1. NaOH (alkoxide formation)

2. CO2

3. H3O+

Ionic metals (3)

K, Li, Na ("In Medieval times, "Kings Lived Nice")

Polar covalent metals (3)

Mn, Cu, Zn (Zinc and Copper Mines)

R-X to R-MgBr (formation of Grignard reagent)

Mg0(s)

R-X to LiX and R-Li (organolithium reagent)

Li0(s)

Alternative way to prepare organolithium reagent R'-X and R-Li to R'-Li and R-X (R-group swapping)

R'-X and R-Li to R'-Li and R-X (R-group swapping)

*R'-X must be: 1° R'-X, 2° R'-X, alkenyl halogen, or aryl halogen

Formaldehyde to 1° alcohol

R-MgBr or R-Li

Aldehyde to 2° alcohol

R-MgBr or R-Li

Ketone to 3° alcohol

R-MgBr or R-Li

Ester (R-C(=O)-OR) to 3° alcohol

1. 2R-Li (NEED 2 equivalents of R-Li to get all starting product to 3° alcohol) -- *2R-MgBr also works

2. H3O+ (H+)

Limitation for R-Li or R-MgX (L-M)

Cannot react with R-X

*Elimination product forms instead

* R-= (Alkene) + R'-H + M-X

H3N: (ammine)

L (2)

H2Ö: (aquo)

L (2)

R3P: (R = alkyl, aryl) (trialklphosphino/triarylphosphino)

L (2)

:C=Ö: (carbonyl)

L (2)

H2C=CH2 (ethylene)

Abr.: CO

L (2)

CH3C(triple bond)N (acetonitrile)

Abr.: MeCN

L (2)