Week 4 Reactions

Question 1

Halogenation

Answer 1

Cl2, AlCl3 OR Br2, FeBr3
————–> —————>

Ortho and para positions

Question 2

Nitrogenation

Answer 2

HNO3, H2SO4
———————>

Meta position

Question 3

Friedels-Crafts Alkylation

Answer 3

t-Butyl-Cl, AlCl3
———————->

t-Butyl, iPr, intramolecularly
NEW C-C BOND

Question 4

Friedels-Crafts Acylation

Answer 4

Acid chloride, AlCl3
—————————->

R: only alkene FGs
NEW C-C BOND

Question 5

SNAR

Answer 5

Nu:
—->

EWG ortho/para to LG
EWG often NO2 or ketone
Use OH-/OR- or SH-/SR- for synthesis

Question 6

Ketone/aldehyde to 3* alcohol

Answer 6

1. RMgBr, Et2O
   - ——————–>
2. H+ wkup

Cannot use on acidic protons: deprotonate and reprotonate
Grignard Addition
NEW C-C BOND

Question 7

Ketone/Aldehyde Reduction

Ketone/aldehyde to 2* alcohol

Answer 7

NaBH4, EtOH

——————->

Question 8

Reversible Carbonyl Addition: Ketone/aldehyde to acetal

Answer 8

ROH, H+ cat.
——————>

Protonate, ROH attack, H+ transfer, LPP, ROH attack, sol

Question 9

Reversible Carbonyl Addition: Ketone/aldehyde to hemiacetal

Answer 9

RO-, ROH
————–>

RO- attack, H-OR protonate

Question 10

Reversible Carbonyl Addition: Ketone/aldehyde to cyanohydrin

Answer 10

NaCN, ROH
—————–>

CN- attack, H-OR protonate

Doesn’t work on esters or carb. acids (+ derivs).

Question 11

Reversible Carbonyl Addition: Ketone/aldehyde to imine

Answer 11

RNH2, pH=5
——————>

Protonate, RNH2 attack, H+ transfer, LPP, sol

Question 12

Reversible Carbonyl Addition: Ketone/aldehyde to enamine

Answer 12

R2NH, pH=5
——————>

Protonate, R2NH attack, H+ transfer, LPP, H+ mvmt to form double bond

Question 13

Acetal Hydrolysis

Answer 13

H3O+
——–>

Protonate, LPP, H2O attack, H+ transfer, LPP, sol

Question 14

Imine Hydrolysis

Answer 14

H3O+
——–>

Protonate, H2O attack, H+ transfer, LPP, sol

Question 15

Enamine Hydrolysis

Answer 15

H3O+
——–>

LPP and protonate, H2O attack, H+ transfer, LPP, sol

Question 16

Imine or enamine to 2* amine

Answer 16

H2, Pd/C
————->

Removing double bond and adding H
Imine Reduction

Question 17

Ketone/aldehyde to 2/3 amine

Answer 17

+ RNH2/R2NH NaBH3CN, pH=5
————————->

Protonate, RNH2/R2NH attack, H+ transfer, LPP, BH3CN attack (pushing double bond up/adding H)
Reductive Amination

Question 18

Wittig: Alkyl halide to ylide

Answer 18

1. PPh3
   - ———->
2. n-BuLi

SN2, deprotonate

Question 19

Wittig: Ylide to alkene

Answer 19

O
||
R R’
——–>

PPh3 LP attack, O LP to PPh3+, CP -> CO
Favors cis alkenes
NEW C=C BOND

Question 20

One-Step Carbonyl Reduction: Clemmensen

Aldehyde/ketone to bottom part of aldehyde/ketone (alkane)

Answer 20

Zn, HCl
———–>

Just “erase” C=O

Question 21

Grignard to carboxylic acid

Answer 21

1. CO2
   - ——–>
2. H+ wkup

R-MgBr attack C in O=C=O, H+ wkup to protonate O:-

Question 22

Transesterification

Ester with R to Ester with R”

Answer 22

ROH, H+
————>

Protonate, ROH attack, H+ transfer, LPP, sol

Question 23

Transesterification: Going backwards

Answer 23

RO-, ROH
————–>

RO- attack, LPP (old) OR’ off

Question 24

Carboxylic Acid Derivative Hydrolysis: Acid chloride to carboxylic acid

Answer 24

H2O
——->

H2O attack, LPP, sol

Question 25

Carboxylic Acid Derivative Hydrolysis: Amide to carboxylic acid

Answer 25

H2O, H+, heat --------------------> Protonate, H2O attack, H+ transfer, LPP, sol

Question 26

Carboxylic Acid Derivative Hydrolysis: Ester to carboxylic acid

Answer 26

1. OH-, H2O - ---------------> 2. H+ wkup OH- attack, LPP, deprotonate with H2O (or ROH), reprotonate with H+ wkup

Question 27

Carboxylic Acid Derivative Hydrolysis: Nitrile to carboxylic acid

Answer 27

H2O (2 equiv.), H+, heat ----------------------------------> Protonate, H2O attack, H+ transfer, LPP, sol

Question 28

Forming acid chloride | Carboxylic acid to acid chloride

Answer 28

SOCl2 ---------> Attack SOCl2, Cl- attack, LPP, sol

Question 29

Reacting Acid Chlorides: Acid chloride to ester

Answer 29

ROH -------> Cl replaced with OR

Question 30

Acid chloride to amide

Answer 30

RNH2 --------> pyr RNH2 attack, LPP, pyr (acting as sol) For 1*: NH3 For 2*: RNH2 For 3*: R2NH

Question 31

Reduction of CADs: Ester to 1* alcohol

Answer 31

1. LAH, Et2O - ----------------> 2. H+ wkup LAH attack, LPP, LAH, H+ wkup LAH double addition (ester with LAH)

Question 32

Reduction of CADs: Carboxylic acid to 1* alcohol

Answer 32

1. LAH, Et2O - ----------------> 2. H+ wkup LAH attack, H+ wkup

Question 33

Reduction of CADs: Amide to amine

Answer 33

1. LAH, Et2O - ----------------> 2. H+ wkup Just "erase" C=O

Question 34

Reduction of CADs: Nitrile to 1* amine

Answer 34

1. LAH, Et2O - ----------------> 2. H+ wkup

Question 35

Acid chloride to 3* alcohol

Answer 35

1. RMgBr - ------------> 2. H+ wkup RMgBr attack, LPP, RMgBr attack, H+ wkup Double addition of Grignards 2 NEW C-C BONDS

Question 36

Ester to 3* alcohol

Answer 36

1. RMgBr - ------------> 2. H+ wkup RMgBr attack, LPP, RMgBr attack, H+ wkup Double addition of Grignards 2 NEW C-C BONDS

Question 37

Partial Reductions: Acid chloride to ketone

Answer 37

RZnBr ---------> RZnBr, LPP "Zignard" NEW C-C BOND

Question 38

Partial Reductions: Ester to aldehyde

Answer 38

1. DIBAL-H, -78* C - ------------------------> 2. H+ wkup Attack DIBAL-H, OR LP to Al, H+ wkup

Question 39

Baeyer-Villiger Oxidation | Ketone to ester

Answer 39

mCPBA -----------> Attack H on mCPBA, O:- on mCPBA attacks C=O, OH LP forms double bond and more substituted C-R attacks O on mCPBA, O:- attacks H on ester BREAKS C-C AND ADDS O Can expand rings