Orgo 1 Reactions

polar protic donor solvents

EtOH, MeOH, H2O, formamide (CONH2 H)

• can dissolve charges

polar, aprotic, donor

DMF, DMSO, CH3CN, acetone, diethlyether

• can dissolve but not stabilize - polar solvents effectively

• usually SN2

Nonpolar donor protic solvent

tBuOH, acetic acid

nonpolar, donar, aprotic solvent

diethylether, THF, ethyl acetate

nonpolar, nondonar, aprotic

hexane, pentane, benzenes, ch3cl

SN2 - substitution nucleophilic bimolecular

SUBSTRATE EFFECTS

• Rate = K [Nu] [substrate]

• Good Lg

  • very weak base

• Backside Attack

  • ALWAYS a change in stereochemistry (inversion)

SN2 - substitution nucleophilic bimolecular

NUCLEOPHILE EFFECTS

• Good Nucleophile →

  • anions (CN-, DMF, DMSO), I- Br-, Cl-, N3-, RS-, OH-, SH2, RSH

  • most are negatively charged

• primary or secondary alkyl halide (NO TERTIARY)

  • beta carbon branching is SLOWER

• good nucleophile CH3>NH2>-OH>F, high electronegativity 

• Larger atom (more diffuses electron cloud) I > Br > Cl > F for nucleophile

• so the periodic trend is Left and Down

• small nucleophile 

LEAVING GROUP EFFECT

• good leaving group (OH<F<Cl<Br<I)

• I > Br > Cl

• OTs is BETTER LG THAN I-

  • SUPPPPPERRRR weak

OTs is o- (o=)2-s-benzene

SN2

SOLVENT EFFECT

• solvent 

  • prefers polar aprotic (F- is better than I-, C > F)

C >N >O >F

--P> S > Cl

—         I

• F > Cl > Br > I

• in polar protic, it flips (I- is better than F-) 

  • can hydrogen bond (SOLVATION)

  • form stronger ion attraction and dissolve faster (lowers energy)

  • STABILIZE NU, making them less reactive to substrate

  • less electronegative, more reactive NU

C >N >O >F

--P> S > Cl

—         I

• I > Br > Cl > F

  • larger ions are effected LESS by solvation

    • less polarizable by solvent

SN1 nucleophile

almost always weak!

• ex: CH3OH

  • in SN2 it was CH3O- , the charge made it strong, but if a charge is present, usually it’ll choose SN2 > SN1. The carbocation is SO reactive it’ll take almost any nucleophile (easy)

SN1 substrate

tertiary > secondary

• no primary, no carbocation

• CARBOCATIONS can undergo REARRANGEMENTS if tertiary or quaternary is adjacent

SN1 solvent

MUST BE POLAR PROTIC

• stabilizing the CARBOCATION

  • need the donating H

• H2O, R-OH

SN1 LG

OTs- > I- > Br- > Cl

E2

tertiary over secondary over primary

• prefer strong base

  • RO-, -OH

• polar aprotic

• strong bulky base

  • t-buO- (hoffman) 

E1

tertiary over secondary

• polar protic

• weak base 

  • H2O, CH3OH, ROH, RCOOH

Peroxide / Hbr with Alkenes

allows for faster antimarkovnikov addition

Step one of Free Radican Chain Reaction

1) Initiation

• formation of the alkoxy radical

• formation of the halide radical\

  • radical reacts with nonradical to SWAP states

• * radicatls are produced from nonradicals 

Step 2 of Free-Radical Chain Reaction

2. Propagation

radicals and nonradicals react to form NEW radicals and non-radicals 

step 3 of free-radical chain reaction

3. termination

2 radicals react to form nonradicals

characteristics of radicals (stability)

tertiary > secondary > primary

• radical goes on more substituted carbon, halide on the lesser when reacting wih alkenes (addition) 

forming trans alkenes from alkynes

2Na + 2NH3

• versus lindlar that does alkyne → cis alkene

Organometallic Compounds

contain a carbon bonded to a metal (C - M)

most common:

• R - Mg - X

  • Grignard reagents

• R - Li

  • Organolithium reagent

formed most often from alkyl and aryl halides

gringard reagent (Mg)

• usually in nonpolar, aprotic 

• NEEDS TO BE APROTIC

  • very reactive with O2, H2O, ROH

  • hexane or Et2O are good

Organolithium reagent 

• Needs to be in an aprotic solvent 

  • very reactive with O2, H2O, ROH

  • hexane or ET2O are good

Organolithium reagent acting as strong bases 

the negative charge on the C allows it to react with things like H-OR, H-OH, CH3OH and TAKE the hydrogen

acetylide anion as nucleophiles ( R - C (tripplebond) C-)

require terminal hydrogen. anion carbon takes H. New negative charge on alkyle carbon can react with an alkyl halide and take that alkyl 

alpha elimination (producing carbenes)

strong base reacts with chloroform to make a Cl - C - Cl (not a full octet but no charge) which can act as a nucleophile and electrophile at the same time! This makes a carbene

Simmons-Smith 

solvent is a benzene (nonpolar, aprotic, acceptor)

• I — CH2 — ZnI

H2 Lindlar catalyst

Definition: Syn hydrogenation of an alkyne to a cis-alkene (partial reduction).
General equation:
RC≡CR' →(H₂, Lindlar)→ RC=C(R') (cis)

H₂, Pd/C catalyst

Definition: Complete hydrogenation of alkenes and alkynes to alkanes.
General equation:
RC≡CR' →(H₂, Pd/C)→ RC₂H–CR'₂H
RCH=CHR' →(H₂, Pd/C)→ RCH₂–CH₂R'

1) O₃, 2) (CH₃)₂S

Definition: Ozonolysis (reductive workup) → cleaves double bonds, giving aldehydes/ketones.
General equation:
RCH=CHR' →(1. O₃, 2. (CH₃)₂S)→ RCHO + R'CHO (or ketones depending on substitution)

HBr

Definition: Markovnikov hydrohalogenation of alkenes (no radicals).
General equation:
RCH=CHR' + HBr → RCH(Br)–CH₂R'

HBr, peroxides

Definition: Anti-Markovnikov addition of HBr via radical mechanism.
General equation:
RCH=CHR' + HBr → RCH₂–CH(Br)R'

Br₂, H₂O

Definition: Halohydrin formation (Br and OH added anti).
General equation:
RCH=CHR' + Br₂/H₂O → RCH(OH)–CH(Br)R'

NaNH₂ / liquid NH₃

Definition: Strong base that deprotonates terminal alkynes or performs double elimination to form alkynes from dihalides.
General equations:

1. RC≡CH + NaNH₂ → RC≡C⁻ Na⁺

2. RCHBr–CHBrR' →(excess NaNH₂)→ RC≡CR'

Mg, diethyl ether

Definition: Formation of Grignard reagents from alkyl or aryl halides.
General equation:
R–X + Mg → R–Mg–X

1) BH₃·THF, 2) H₂O₂, NaOH

Definition: Hydroboration–oxidation of alkenes → alcohol, anti-Markovnikov, syn.
General equation:
RCH=CHR' → RCH₂–CH(OH)R'

1) disiamylborane, 2) H₂O₂, NaOH

Definition: Hydroboration–oxidation of alkynes, giving aldehydes from terminal alkynes.
General equation:
RC≡CH → R–CH₂–CHO

Na metal, liquid NH₃

Definition: Dissolving-metal reduction of alkynes → trans-alkenes.
General equation:
RC≡CR' →(Na/NH₃)→ RC=CR' (trans)

Hg²⁺ (catalyst), H₃O⁺

Definition: Mercury-catalyzed hydration of alkynes → ketones via enol–keto tautomerization (Markovnikov).
General equation:
RC≡CH → R–CO–CH₃

CH₂I₂, Zn/Cu (Simmons–Smith)

Definition: Cyclopropanation of alkenes.
General equation:
RCH=CHR' + CH₂I₂/Zn–Cu → cyclopropane ring fused onto alkene

KOCl(CH₃)₃, DMSO (Swern oxidation)

Definition: Oxidation of alcohols → aldehydes or ketones (mild, no over-oxidation).
General equation:
RCH₂OH → R–CHO
R₂CHOH → R₂C=O

1) O₃, 2) H₂O₂ / H₂O

Definition: Oxidative ozonolysis → carboxylic acids (instead of aldehydes).
General equation:
RCH=CHR' → RCO₂H + R'CO₂H

Br₂

Definition: Halogenation of alkenes → vicinal dibromides (anti-addition).
General equation:
RCH=CHR' + Br₂ → RCH(Br)–CH(Br)R'

1) Hg(OAc)₂, H₂O; 2) NaBH₄ / NaOH

Definition: Oxymercuration–demercuration → Markovnikov hydration of alkenes without rearrangement.
General equation:
RCH=CHR' → RCH(OH)–CH₂R'

K2Cr2O7/ H2SO4 excess

turns aldehydes into carboxylic acids (21 in HW)

NMMO w/ cat: OsO4

alkene → alcohols added (cis to one another)

acid‑catalyzed opening of the epoxide

adds OH. Nucleophile is added to MORE substituted

mCPBA + CH2Cl2 with an alkene

forms a propane ring with oxygen (epoxide)

PCC

can make an alcohol → aldehyde

Na+ H- + HO-R (w/ K+ -OtBu solvent (polar aprotic))

formation of an alkoxide or mercaptide

Na+ -OR

Polar effect on alcohol acidity

Having an F incrreases the acidity. shorter chains are more acidic, S > O, alcohol CB are VERY acidic (h2O good lg)

H2SO4 or H3PO4 with an alkyl alcohol

dehydration and alkene formation

alcohols with HX

form alkyl bromides + water through SN1

sulfonate ester derivative of alcohols (O-S(=O)2 -O) with pyruvate in solution

removes alcohol group. sulfonate ester is a very good LG.

SOCl2 rxn with alcohols

fomation of primary halides. pyruvates are usually solvents

Ph3P-Br + Alcohol

Formation of alkyl bromide through inversion (SN2)

Phosphate LG (O-P(=O)(-OH) -OH

makes OH into a good LG and makes carbocation (E1 or SN1 rxns)

SH in the presence of HNO3 or CrO3

Oxidizes it to S(=O)2 ( -O)2

H5IO6 with alcohols

Acts similarly to ozonolysis and forms carboneles (aldehydes)

Basic‑catalyzed opening of the epoxide

Adds oh and nucleophile. Nucleophile attacks the less substituted

CrO3 H2O

Alcohol to carboxylic acid (harsh oxidizing conditions remove both h’s)