OH OH CrO3, H2SO4 H2O, Acetone

O OH 1) NaBH4 2) H3O+

OH

O OH

H3C Cl CH CH3 CH3

H3C excess KMnO4 heat () (+ some o- isomer)

HO

O C O C OH

Br NBS peroxides: (PhCO2)2 NaOH EtOH

H Cl O (MCPBA)

O O O CH3CH2O-K+ CH3CH2OH OH OCH2CH3

OH H3C OH SOCl2 Cl AlCl3 CH3 H3C

OH CH3

O O Cl AlCl3 1) CH3MgBr 2) H3O+ 3) PBr3 Br CH3

How many ways can you come up with to make the following molecules? (For practice, think of some other examples on your own and see how many ways you can come up with to make them.) Here are a few possibilities. Next work on the precursors. Br NBS, peroxides CH3

NaOH OH LiAlH 4 NaBH4 H

O OH

KMnO4

O H HX MgBr

O H

Again, these are some of the possibilities. Figuring out schemes like these for different target molecules with help you when you are faced with a more complex molecule.

1) Hg(OAc)2 H2O POCl3 pyridine HO O H3C 1) O H 2) NaBH4

OH

NaBH4

O O H3C Cl

AlCl3

2) H3O+

MgBr

Explain the following reactions with detailed mechanisms.

NH2 HNO3 H2SO4

NH2 only product, slow reaction, low yield NO2

H+ NH2 NH3 Direct attachment of positive charge to ring gives inductive electron-withdrawing effect, and thereby 1) deactivates the ring and 2) gives the meta-substituted product. Draw the resonance structures of the possible intermediates to check this out. When chemists need to nitrate aminobenzenes, they usually use other non-acidic nitrating reagents like CH3CH2ONO2 (but you dont need to know this) or they first convert the amine to an amide by reaction with an acid chloride or an anhydride (you dont need to now this yet).

H2SO4

H+ H3C

Two electrophilic addition steps followed by one electrophilic aromatic substitution step. Redrawing the intermediate helps you see where the last substitution occurs.

HSO4-

Prepare the following compounds from benzene, inorganic reagents, and organic compounds with 4 or fewer carbons. OCH3 a) H OH OCH3 OCH3 b) c) H Br g) OCH3 i) j) OCH3 d) OH e) OCH3 d) OH e) SO3H f)

H h) OCH3

CH3 g)

CH3

CH3

CH3 g)

SO3H f)

MgBr

Br

a) PCC; b) PBr3; c) NBS,(PhCO2)2; d) NaH, MeBr; e) NaOH, heat; f) H2SO4/SO3; g) CH3Cl, AlCl3; h) H2C=O; i) Mg, Ether; j) Br2, FeBr3 Any way you go about it, it looks like seven steps. If you make the ether at an early stage of the procedure, you avoid problems with using NaH in the presence of the aldehyde or the alkyl bromide. Addition of formaldehyde to a grignard reagent is a nice way to make a primary alcohol with an extra carbon. Remember that the ArSO3H to ArOH conversion can only tolerate alkyl substituents on the aryl ring a) MCPBA b) NaOH/EtOH (E2) c) NBS/peroxides d) HNO3/H2SO4 e) H2/Pd g) NO2 h) OH Cl NO2 i) Cl MgBr NO2 j) Cl Br NO2 k) Cl Br NH2 NH2 Figure out the epoxide group and the side chain first (i.e., as the first precursor to the product). Remember that epoxides open easily under acidic conditions and that most of the electrophilic aromatic subst. steps we know use strong Lewis acids. Note that the branching on the side chain rules out simple Friedel-Crafts alkylation. The top route takes seven steps and looks pretty good. The bottom route is longer, and steps l) and m) will probably give mixtures. Step j) might also give problems with competing formation of the ArMgCl Grignard. Step o) probably takes us to a dead end. l) o) Cl NO2 NO2 m) O n) NH2 Cl NO2 d) Cl f) Cl2, FeCl3 g) (CH3)2CHCOCl, AlCl3 h) POCl3, pyridine i) (CH3)2CHCHO d) (then H3O+) j) Mg, Ether k) O3(you dont have to know this one) l) Br2/FeBr3 m) Cl2/FeCl3 n) H2/Pd o) PCC

Cl

O Cl NO2 a) b) c)

Br Cl NO2 e)

O f)

Cl

Cl