An organic chemistry reaction exercise based on the web site - PowerPoint Presentation

Slide1

An organic chemistry reaction exercise based on the web site

http://murov.info/rxnmaponline.pdf (for more info, see the last 5 slides). Several exercises are suggested for students to improve competency in organic reactions at that site. The first one is: For each numbered reaction, classify the reaction by mechanism (e.g., substitution, nucleophilic) and list the reagents, conditions, regioselectivity, stereoselectivity and restrictions associated with the reaction. This exercise is intended to facilitate the suggestion that students list the reagents needed to enable the reactions. The reactions appear in an order determined by a random number generator (1- 107). For suggestions and comments, please e-mail murovs@yosemite.edu .

Organic Chemistry Reaction Exercises

”Organic chemistry nowadays almost drives me mad. It gives me the impression of a primeval tropical forest, full of the most remarkable things, a monstrous and boundless thicket, a dreadful, endless jungle with no way of escape, into which one may well dread to enter for there seems no way out.”

Friedrich Wöhler(1800 – 1882)founded organicchemistry in 1828.

Slide2

48 (D8) Elimination. 1. CH3I (excess) 2. Ag2O/H2O 3. D , amine

g alkene, Hofmann (least substituted) product.

48 (D8)

35 (F10)35 (F10) Electrophilic addition.HX, 2 moles,alkyne

g

dihalide (geminal).

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide3

For each reaction #, state the

rxn. type and the reagents needed to enable the rxn.The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

62 (K13) Addition-elimination.H+/ROH, carboxylic acid

g ester, position of equilibrium important in this reaction.

101 (F10)62 (K13)

101 (F6) (Ph)

3

P=CHR, Wittig reagent synthesized from

1. Ph

3

P +

RBr

2.

RLi

, aldehyde or ketone

g

alkene.

Slide4

81 (A9)41 (F7, A2)

81a (A9) Mg/Et2O, alkyl halide

g organometallic, formation of Grignard, water must be excluded81b (A9) Li/Et2O, alkyl halide g organometallic formation of organolithium compound, more reactive than Grignard, water must be excluded.

41 (F7, A2) Nucleophilic Addition.1. RMgX 2. H

+

/H

2

O, aldehyde or ketone g alcohol, Grignard reaction.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide5

51 (F10)7 (L2)

51 (F10) Addition, elimination.NH2R, aldehyde or

ketone g “imine”, R’s commonly used to make classic derivatives of carbonyls yield oximes (R = OH, NH2OH = hydroxylamine), hydrazones (R = NH2 or NHR’, if 2,4-dintrophenylhydrazine is used, a 2,4-dinitrophenylhydrazone results), semicarbazones (R = NHCONH2, NH2NHCONH2 =

semicarbazide).7 (L2) PhY where Y is a strong activator, aromatic

g

aromatic derivatives (e.g., OH or NH

2

) for electrophilic aromatic substitution.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide6

56 (K10)85 (B9)

56 (K10) Addition, elimination.NH3 (or RNH

2 or R2NH), anhydride g amide.

85 (B9) ReductionTsCl/pyridine 2. LiAlH4, alcohol

g

alkane.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide7

105 (L12) D, carboxylic acid g carbon dioxide + residue (usually aromatic or b-keto carboxylic acids, others do not easily decarboxylate).

105 (L12)

55 (J16)55 (J16) Addition, elimination. ROH, acyl halide g ester.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide8

61 (K11) Addition, eliminationNH3, carboxylic acid g amide, primarily an industrial reaction as it requires extreme conditions.

61 (K11)

79 (I13) 79 (I13) Oxidation.CrO3/H2SO4 or Na2

Cr2O7/H2SO4 or KMnO4/H2SO4 for 1

o

alcohols,

alcohol

g

carboxylic acid.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide9

15 (K1) Nucleophilic arom. subst.HBF4/D, aromatics g aromatic fluorides

15 (K1)

93 (I10)93 (I10) Reduction.1. DIBAH (diisobutylaluminium hydride)/-80oC

2. H+, nitrile g aldehyde

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide10

104 (L6) Br2/OH-, Hofmann rearrangement, amide g amine with one less carbon.

104 (L6)

19 (C13)Nucleophilic substitution. 19a (C13) OH-, alkyl halide g alcohol, SN2 for 1

o although steric hindrance in the nucleophile or alkyl halide promotes elimination, 3o gives elimination.19b (C13) H2O, alkyl halide g alcohol, SN1 for 3

o

, can rearrange, competes with E1.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide11

26 (E6) Nucleophilic substitution. 1. NH2- 2. RX , alkyne and alkyl halide g alkyne, 3o halides eliminate rather than substitute and elimination is prevalent for 2o

halides26 (E6)

43 (H7)43 (H7) Nucleophilic addition.NaCN/HCl, aldehyde or ketone g

cyanohydrin, forms cyanohydrin that can be hydrolyzed toα-hydroxycarboxylic acidFor each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide12

29 (K3) H+/H2O, acetal or ketal g hemiacetal or hemiketal, reversible, see # 28 (K2), 39, 40 (J3)

29 (K3)

77 (E11)77a (E11) Oxidation.KMnO4/OH-, syn-addition, alkene g

diol.b (E11) 1. OsO4 2. H2O2, syn-addition, alkene g diol.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide13

60 (I16) Addition, Elimination. SOCl2 or PCl3 or PCl5 or PBr3, carboxylic acid

g acyl halide. 60 (I16)

92 (I8)92a (I8) Reduction.H2/Pd/C, nitrile

g amine.b (I9) 1. LiAlH4 2. H2O, nitrile g amine

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide14

1 (D1) Electrophilic arom. subst.H2SO4 (can be reversed, see # 2 (E1)), aromatic g aromatic derivatives.

1 (D1)

5 (D4)5 (D4) Electrophilic arom. subst.RX/AlCl3, aromatic

g aromatic derivatives, Friedel-Crafts alkylation, can rearrange and undergo multiple substitution, does not work when ring is deactivated or contains an amino group.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide15

88a (E12) Reduction.1. LiAlH4 2. H3O+, aldehyde or ketone g alcohol.

b (E12) 1. NaBH4 2. H3O+, aldehyde or ketone g alcohol.c (E12) H2/Raney Ni, aldehyde or ketone

g alcohol88 (E12)64 (L11)

64 (L11) Addition, Elimination.NH3 (or RNH2 or R2

NH), ester

g

amide.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide16

63 (K14) Addition, elimination.H+/H2O, ester g carboxylic acid, position of equilibrium important in this reaction.

63 (K14)

68 (H18)68 (H18) Addition, elimination.1. R’2CuLi/Et2O/-78oC

H2O, acyl halide and organometallic g ketone,with Gilman reagent, addition stops at ketone level.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide17

45 (G4) Elimination. see #42 (G7), alcohol g alkene.

45 (G4)

47 (C11)47a (C11) Elimination.H2SO4 or H3PO4, alcohol

g alkene, Zaitsev product with thermodynamically favored stereochemistry dominant, E2for 1o halides, E1 for 2o and 3o halides, rearrangement possible.

b (C11) POCl

3

/pyridine/

O

o

C

,

alcohol

g

alkene, milder conditions than 47a, use of this catalyst avoids rearrangements, Zaitsev product with thermodynamically favored stereochemistry dominant, E2 reaction.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide18

32a (C11) Addition. H+ (H2SO4 or H3PO4

)/H2O, alkene g alcohol, electrophilic Markovnikov addition with possible rearrangement and competing reactions.b (C11) 1. Hg(OAc)

2, THF, H2O 2. NaBH4 , alkene g alcohol, Markovnikov without rearrangement.c (C11) 1. BH3 2. OH-, H2O2

, H2O, alkene g alcohol, anti-Markovnikov orientation without rearrangement.

32 (C11)

78 (F12)

78a (F12) Oxidation. for 2

o

alcohols - CrO

3

/H

2

SO

4

or Na

2

Cr

2

O

7

/H

2

SO

4

or KMnO

4

/H

2

SO

4

, alcohol

g

ketone.

b (F12) for 1

o

alcohols - PCC (pyridinium chlorochromate), alcohol

g

aldehyde.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide19

18a (C14) Nucleophilic subst.NH3, alkyl halide g amine. The direct synthesis of amines from halides is subject to many problems including multiple substitution. Generally, alternatives (e.g., 18b, 18c) should be used.b (C14) 1. Phthalimide/OH

- 2. RX 3. NH2NH2, alkyl halide g amine, Gabriel sy nthesis

of primary amines.c (C14) 1. NaN3 2. Na/ROH or LiAlH4, alkyl halide g amine. 18 (C14)

For each reaction #, state the rxn. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

58 (I12)

58 (I12) Addition, elimination

ROH, anhydride g ester.

Slide20

33 (E14) Addition (electrophilic)X2, alkene g dihalide,anti-addition, only practical forX = Cl or Br

33 (E14)

16 (L1)16 (L1) Nucleophilic arom. subst.H3PO2, aromatics

g aromatic derivatives.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide21

86 (G2) Reduction.Sn/HCl, aromatic nitro compound g aromatic amine.

86 (G2)

22 (C16)22 (C16) Nucleophilic substitution. OR-, alkyl halide g ether, Williamson ether synthesis, elimination possible and prevalent for 3o halide.

For each reaction #, state the rxn. type and the reagents needed to enable the rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide22

9 (E3) Free radical arom. subst.NBS (N-bromosuccinimide), aromatics g aromatic derivatives, good for benzylic and allylic bromination.

9 (E3)

50 (E10)50 (E10) Addition, elimination.1. NH3 (or RNH2)/H+ 2. H

2/Ni or hydride such as NaBH3CN, aldehyde or ketone g amine, reductive amination, technically this should be classed as two reactions with the addition-elimination (51 (G11)) first and the hydrogenation second.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide23

98 (B4) Δ for some, alkene + diene g cyclohexene, Diels-Alder reaction, a concerted syn addition that also falls under classifications of pericyclic and [4 + 2] cycloaddition reactions, electronic releasing groups on the diene and electron- withdrawing groups on the dienophile generally increase the rate of reaction. The diene must be capable of achieving an s-cis conformation and cyclic dienes such as cyclopentadiene react rapidly. There is a stereochemical preference for electron withdrawing groups on the dienophile to end up in the endo position.

98 (B4)

For each reaction #, state the rxn. type and the reagents needed to enable the rxn.The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide24

59a (J11) Addition, elimination.RCOCl (with conjugate base of acid), carboxylic acid g anhydride.b (J11) D for formation of intramolecular anhydrides such as phthalic anhydride

59 (J11)

For each reaction #, state the rxn. type and the reagents needed to enable the rxn.The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide25

106 (K19) 1. OR- 2. R’Br 3. H+/H2O/D, b-keto ester

g ketone, acetoacetic ester synthesis (also consider malonic ester synthesis).

106 (K19)11 (I1)11 (I1) Free radical arom

. subst.CuCl or CuBr, aromatics g aromatic halides, Sandmeyer reaction.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide26

80a (H12) Oxidation.CrO3/H2SO4 or Na2Cr

2O7/H2SO4 or KMnO4/H

2SO4, aldehyde g carboxylic acid.b (H12) 1. Ag2O/NH3 2. H3O+ Tollens test for aldehydes yields silver mirror, aldehyde

g carboxylic acidc (H12) Cu2+/sodium tartrate, aldehyde g carboxylic acid, Fehling’s test for aldehydes yields red Cu2O.d (H12) Cu

2+

/sodium citrate, aldehyde

g

carboxylic acid, Benedict’s test for aldehydes yields red Cu

2

O.

80 (H12)

69 (K18, A3)

69 (K18, A3) Addition, elimination.

1.RMgX/Et2O 2. H

+

/H

2

O, acyl halide and organometallic

g

3

o

alcohol.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide27

6 (D5) Electrophilic arom. subst.Acid chloride/AlCl3 or acid anhydride/AlCl3,

aromatic g aromatic derivatives, Friedel-Crafts acylation, no rearrangement or multiple substitution, does not work when ring is deactivated or contains an amino group, carbonyl can be reduced to CH2 (see #87 (C9)).

6 (D5)66 (K9)

66a (K9) Addition, elimination.H+/H2O or OH-/H2O, nitrile

g

amide, mild conditions as strong conditions yield carboxylic acids

b (K9) H

+

/ROH, nitrile

g

N-substituted amide, Ritter reaction, does not work with 1

o.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide28

14 (J1) Nucleophilic arom. subst. KI, aromatics g aromatic iodides.

14 (J1)

97 (I9)97 (I9) Reduction.1. LiAlH4 2. H2O, amide g amine.

For each reaction #, state the rxn. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide29

67a (K11) Addition, elimination.H+/H2O, amide g carboxylic acid.b (K11) 1. OH-/H2O 2. H

+/H2O, amide g carboxylic acid.

67 (K11)2 (E1)

2 (E1) Electrophilic arom. subst.H3O+/D, aromatic g aromatic derivatives.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide30

4 (D3) Electrophilic arom. subst.X2/FeX3 (or AlX3), aromatic

g aromatic derivatives.

4 (D3)25 (F17, A2))25 (F17, A2) Nucleophilic subst.RMgX

/Et2O 2. H+/H2O, oxirane g alcohol, Grignard reaction, works best on unsubstituted carbon and can give mixtures. Organocuprates (Gilman reagents) are better.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide31

102 (H13) 1. X2/OH- 2. H+, methyl aldehydes and ketones g haloform + carboxylic acid, haloform reaction used to test for methyl ketones (and acetaldehyde and ethanol and other 2

o alcohols).

102 (H13)83 (B6)83 (B6) Reduction.H2/Pt or Pd or Ni, alkyne

g alkane. For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide32

17 (B18) Nucleophilic subst.CN-, alkyl halide g nitrile.

17 (B18)

71 (J7, A3)71 (J7, A3) Addition, elimination.R’MgX/Et2O H+/H2

O, nitrile and organometallic g ketone.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide33

76 (D11) Addition, elimination.RCO3H, alkene g oxirane.

76 (D11)

46 (B13)46a (B13) Elimination.strong base, strong nucleophile such as OH-/ROH, alkyl halide g alkene, Zaitsev product unless R is bulky such as t-butyl or X is fluorine, E2 for 1

o halide competes with SN2, E2 for 3o halide, anti elimination, thermodynamic alkene favored but decreases as base strength increases due to earlier TS .b (B13) poor base, poor nucleophile such as H2O, alkyl halide

g

alkene, Zaitsev product with thermodynamically favored stereochemistry dominant, doesn’t work for 1

o

halides, competition between E1 and S

N

1 for 2

o

and 3

o

halides.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide34

31a (C12) H+ (H2SO4 or H3PO4)/ROH, alkene

g ether, electrophilic Markovnikov addition with possible rearrangement and competing reactions.b (C12) 1. Hg(O2CCF3)2, ROH

2. NaBH4, alkene g ether, alkoxymercuration reaction, Markovnikov addition without rearrangement. 31 (C12)

95 (I13)

95 (I13) Reduction.

DIBAH (

diisobutylaluminium

hydride)/-80

o

C

H

+

, ester

g

aldehyde.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide35

42 (G7) Nucleophilic addition. H+ or OH-, aldehyde or ketone g b

-hydroxycarbonyl compound (aldol), aldol addition of conjugate base of carbonyl to carbonyl. If R’s present are aromatic, addition product eliminates to give enone. If R’s are not aromatic, elimination will occur with heating. If elimination occurs, the reaction is called an aldol condensation. Useful primarily when only one kind of a hydrogen is present.

42 (G7)For each reaction #, state the rxn. type and the reagents needed to enable the

rxn.The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide36

24 (F15)24a (F15) Nucleophilic subst.H

3O+, oxirane g diol, overall from the alkene yields anti-addition, with an alcohol instead of water, alcohol adds to most substituted carbon (Markovikov orientation) with anti-addition.

b (F15) OH-, oxirane g diol, overall from the alkene yields anti-addition, with an alcohol instead of water, alcohol adds to least substituted carbon (anti-MarkoVikov orientation) with anti-addition. For each reaction #, state the

rxn. type and the reagents needed to enable the rxn.The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide37

70 (I17, A3) Addition,elimination.RMgX/Et2O H+/H2O, ester and organometallic

g 3o alcohol.

70 (I17, A3)37, 38 (I4)37,38 (I4) Electrophilic addition.

H+/H2O or OH-/H2O reversible formation of hydrate, aldehyde and ketones D hydrates. Equilibrium strongly favors carbonyl for ketones but is very structure dependent for aldehydes (formaldehyde - 99.99% hydrate and acetaldehyde - 58% hydrate).

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide38

3 (D2) Electrophilic arom. subst.HNO3/H2SO4 produces NO2+

, aromatic g aromatic derivatives.

3 (D2)30 (B11)30a (B11) Electrophilic addition.HX, alkene

g alkyl halide, electrophilic Markovnikov addition.b (B11) Free radical.HBr/peroxides, alkene g alkyl halide, free radical mechanism yields anti-Markovnikov orientation.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide39

44 (M7, A2) Nucleophilic addition.RMgX + CO2 H+/H2

O, carbon dioxide g carboxylic acid, Grignard reaction.

44 (M7, A2)84 (D7)84a (D7) Reduction.H

2/Lindlar’s catalyst (palladium precipitated on CaCO3 and treated with Pb(C2H3O2)2 and quinoline), alkyne g alkene, poisoned catalyst necessary to prevent addition of 2nd mole of H

2

, syn-addition.

b (D7) Na or Li/NH

3

, non-terminal alkyne

g

alkene, gives anti-addition resulting in trans alkene.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide40

39,40 (J3) Electrophilic addition.H+/ROH reversible formation of hemiacetal and hemiketal, aldehyde and ketones D hemiacetals and hemiketals, hemiacetals and hemiketals are generally unstable and, except for sugars, not isolated. Sugars usually exist in cyclic hemiacetal or hemiketal form. Addition of second molecule of alcohol (28 (K2), 29 (K3)) to hemiacetals and hemiketals in reversible substitution reaction yields acetal or ketal. Especially important as blocking or protecting group when ethylene glycol is used to form cyclic acetal or ketal.

39, 40 (J3)

For each reaction #, state the rxn. type and the reagents needed to enable the rxn.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide41

34 (F10) Electrophilic addition.H2/Lindlar’s catalyst X2, alkyne g

dihalide (vicinal). reaction.

34 (F10)103 (K8)103 (K8) P2O5

or SOCl2, amide g nitrile.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide42

100 (B18)100 (B18) 1. Li/Et2O 2. CuI 3. RʹX, alkyl halide uses Gilman reagent to make symmetrical and unsymmetrical hydrocarbons.

For each reaction #, state the

rxn. type and the reagents needed to enable the rxn.The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

28 (K2) H+/ROH, hemiacetal or hemiketal g acetal or ketal, reversible, see # 39, 40 (J3), hemiacetals and hemiketals are generally unstable and, except for sugars, not isolated.

28 (K2)

Slide43

57a (J12) Addition, elimination.H+/H2O, anhydride g carboxylic acid.b (J12) 1. OH-

/H2O 2. H+/H2O, anhydride g carboxylic acid.

57 (J12)73 (B3)

73 (B3) Oxidation.O3 2. Zn/HCl, alkene g

aldehydes and/or ketones depending on alkene substitution.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide44

87a (C9) Zn(Hg)/HCl/D, aldehyde or ketone g alkane, Clemmensen reduction for acid insensitive compounds. b (C9) NH2

NH2//OH-/D, aldehyde or ketone g

alkane, Wolff-Kishner reduction for base insensitive compounds.c (C9) 1. HS(CH2)2SH/HCl 2. H2/Raney Ni, aldehyde or ketone g alkane, for compounds insensitive to acid or base87 (C9)

For each reaction #, state the rxn. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide45

12 (L4)12 (L4) Free radical.CuCN, aromatics

g aromatic nitriles, Sandmeyer reaction.

For each reaction #, state the rxn. type and the reagents needed to enable the rxn.The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

49 (E8) Elimination.NaNH2/NH3 or K t-butoxide/DMSO, (di)halide g alkyne.

49 (E8)

Slide46

65a (J10) Elimination.H+/H2O, nitrile g carboxylic acid.b (J10) 1. OH-

/H2O 2. H+/H2O, nitrile g carboxylic acid.

65 (J10)13 (J1)

13 (J1) Nucleophilic arom. subst.H3O+/D

, aromatics

g

aromatic phenols.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide47

52 (H15) Addition, elimination.RCOO-, acyl halide g anhydride.

52 (H15)

90 (G16)90a (G16) Reduction.LiAlH4 H3O+

, acyl halide g alcohol.90b (G16) H2/Pd, acyl halide g alcohol.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide48

53 (K10) Addition, elimination.NH3 (or RNH2 or R2NH), acyl halide g amide.

53 (K10)

23 (C17)23 (C17) Nucleophilic substitution.TsCl/pyridine CN

-, alcohol g nitrile.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide49

94 (H12) Reduction.LiAlH4 H+, carboxylic acid g

alcohol. 94 (H12)

96 (H14)96 (H14) Reduction.LiAlH4

H+, ester g alcohol.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide50

8 (A5) H2O or any good proton donor, organometallic g alkane.

8 (A5)

91 (H15)91 (H15) Reduction.LiAlH[OC(CH3)3]3H, -78oC

H+ or H2/partially deactivated Pd similar to Lindlar’s catalyst (Rosenmund reduction), acyl halide g

aldehyde.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide51

74 (H2) Oxidation.NaNO2/HCl, amine g diazonium salt, for 1o aromatic amines.

74 (H2)

10 (B13)10 (B13) X2/hn or

D, alkane g alkyl halide, free radical chain reaction, multiple substitution, because of limited selectivity, useful primarily when there is only one type of hydrogen or for more reactive hydrogens (e.g., benzylic and allylic).

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide52

75a (F3) Oxidation.KMnO4/H3O+/D, alkyl benzene with

a alkyl hydrogens g a benzoic acid.b (F3) K2

Cr2O7/H3O+/D, alkyl benzene with a alkyl hydrogens g a benzoic acid.

75 (F3)

54 (J15)

54a (J15) Addition, elimination.

H

+

/H

2

O,

acyl halide

g

carboxylic acid.

b (J15) 1. OH

-

/H

2

O

2. H

+

/H

2

O,

acyl halide

g

carboxylic acid.

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide53

36a (E9) H2O/H2SO4 for disubstituted alkynes, H2O/H2SO4

/HgSO4 for terminal alkynes, alkynes g ketones (except ethylene g acetaldehyde), Markovnikov orientation.b (E6) 1. BH3 2. H

2O2/OH- for disubstituted alkynes, substitute disiamylborane for borane for terminal alkynes, alkynes g aldehydes and ketones, anti-Markovnikov orientation. 36 (E9)

For each reaction #, state the rxn. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide54

99 (C5)99a (C5) 1. CH2N

2/D or hn

alkene, carbene + alkene g cyclopropane, generally a syn addition, also see 107 (L18).b (C5) 1. CH2I2/Zn(Cu) 2. alkene, Simmons-Smith reagent, carbenoid + alkene g cyclopropane (also see 107 (L18).

For each reaction #, state the rxn. type and the reagents needed to enable the rxn.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide55

21a (D13) Nucleophilic subst. 1. Na 2. R’X, alcohol g ether, Williamson ether synthesis, elimination possible and exclusive for 3o halide, prevalent with a 2o halide.b (D13) 1.

TsCl/pyridine 2. OR-, alcohol g ether.c (D13) H2SO

4, alcohol g ether , useful for symmetrical ethers and 3o ROH with 1o ROH, competes with elimination. 21 (D13)

For each reaction #, state the rxn. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide56

20 (C15)20a (C15) Nucleophilic subst.HX, alcohol

g alkyl halide, 1o usually go SN2 (except that HCl does not work as Cl- is a weak nucleophile) and 3o

usually go SN1 with rearrangement and competing elimination possible.b (C15) PX3 or SOCl2, alcohol g alkyl halide.c (C15) 1. TsCl/pyridine 2. X-, alcohol g alkyl halide.

For each reaction #, state the rxn. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide57

72 (J17) Addition, elimination. RO-, ester g b-keto ester, Claisen condensation, ester must have 2

a hydrogens (the 2nd one prevents a reverse reaction).

72 (J17)107 (L18)107 (L18) 1. t-butoxide 2. alkene, dichlorocarbene + alkene

g dichlorocyclopropane, a syn addition, also see 99 (C5). For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide58

82 (B7) Reduction.H2/Pt or Pd or Ni, alkene g alkane, syn-addition.

82 (B7)

89 (E14)89 (E14) Reduction.LiAlH4 H2O, oxirane

g alcohol, hydride attacks least substituted carbon. For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

The problem # is followed by the road map location. Hit the space bar for the solution and again to advance to the next problem.

Slide59

27a (G7) 1. LDA (lithium diisopropylamide) 2. R”X, aldehyde or ketone g alkylated aldehyde or ketone, works best with 1o halides, multiple substitution possible, with 2 types of α hydrogens, orientation depends on conditions for kinetic vs thermodynamic control but normally gives the kinetic enolate.b (G7) 1. pyrrolidine (or other 2

o amine)/H+ 2. R”X 3. H3O+, aldehyde or ketone g alkylated aldehyde or ketone, alkylation usually takes place on least substituted side of the original carbonyl position, Stork enamine reaction.

27 (G7)

For each reaction #, state the

rxn

. type and the reagents needed to enable the

rxn

.

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Slide60

Abstract: The

Reaction -Map of Organic Chemistry has been designed to give organic chemistry students an overview of most of the reactions needed for the organic chemistry course. The chart has been partially organized according to the periodic table on the horizontal axis and according to carbon oxidation level on the vertical axis. In addition the carboxyls are grouped vertically according to decreasing reactivity and carbon - carbon bond forming reactions are emphasized with bold arrows. The chart provides a study aide for students and should help students develop synthetic routes from one functional group to another. The chart should be especially useful for students studying for the final examination for the two semester organic chemistry course. In addition to the chart, three keys are available that organize the reactions according to mechanism, functional group preparations and functional group reactions. Chemistry can be thought of as a search for order in matter and this chart attempts to provide some insight into the order that exists in organic chemistry. Steven Murov, 06/08/12, http://murov.info/ , http://murov.info/resume.htm

, murovs@mjc.eduThe article on the Reaction-Map of Organic Chemistry was originally published in the Journal of Chemical Education (Murov, S. J. Chem. Ed., 2007, 84

(7), 1224). The supporting information including the Reaction-Map were published online only. This web site includes only the supporting information and is published with permission from J. Chem. Ed. 2007, 84(7), 1224. Copyright 2007 American Chemical Society. The following web sites are available to J. Chem. Ed. subscribers. http://pubs.acs.org/doi/pdf/10.1021/ed084p1224 http://pubs.acs.org/doi/suppl/10.1021/ed084p1224/suppl_file/jce2007p1224w.pdf

Slide61

KEYS TO REACTION-MAP OF ORGANIC CHEMISTRY

General Organization Left to right, compounds in the colored regions are arranged according to the periodic table. Organolithium and Grignard reagents are under lithium and magnesium but these reagents are used elsewhere on several bold arrows for the synthesis of C-C bonds. Carbon compounds that do not contain other elements (besides hydrogen) are under carbon, carbon - nitrogen (and C, N, O) compounds are under nitrogen, carbon - oxygen compounds are under oxygen and carbon - halogen (and C, O, X) compounds are under fluorine and the halogens. From top to bottom, within groups, the compounds are arranged according to the oxidation level of the compound. The oxidation level of organic compounds is somewhat of a complex concept. Even for propane, the carbons technically have different oxidation states. For the purposes of grouping compounds by oxidation level for this chart, the general guideline used has been that oxidation involves a decrease in the number of bonds to carbon from an atom less electronegative than carbon (most frequently hydrogen) and/or an increase in the number of bonds from carbon to atoms more electronegative than carbon (most frequently N, O, X). Reduction is the reverse. If two carbons change, then the sum of the changes must be considered. When water is added to a double bond, one carbon gains a hydrogen and the other an oxygen and the net oxidation level of the molecule does not change. The increase in carbon oxidation level is indicated by color with red the lowest and blue the highest (or by the degree of darkness in the b/w version).

Slide62

This organization results in five groups including: 1. alkanes (and organometallics), 2. alkenes (and alkene addition products such as alcohols, ethers and halides), aromatics and amines, 3. alkynes (and alkyne addition products such as carbonyls), 4.

carboxyls and 5. carbon dioxide and tetrahalomethane. For the purposes of organizing the numbering of the reactions for this key, the reactions have been grouped according to mechanism of the first step of the reaction. Many reactions fall into more than one group. The addition of hydrogen to p bonds is usually discussed in texts along with electrophilic additions to p bonds but here the hydrogen additions have been placed in the reduction category. Reductions with hydrides such as LiAlH4 are often grouped with nucleophilic additions but here have also been included in the reduction category. The reactions are listed in the order substitution, addition, elimination, addition-elimination, oxidation, reduction, concerted and miscellaneous. To facilitate the finding of reactions from any of the keys that follow, a roadmap grid has been included. For example, the addition of HX to an alkene is represented by reaction 30 which is in grid position B11. Three keys are have been designed to accompany the map. The keys are arranged according to mechanism, functional group preparations and functional group reactions. Reactions in the three keys contain the reaction numbers and grid locators. Outside of the main region, bold arrows indicate reactions that form C-C bonds. In the color version, products that result from carbon - carbon bond formation are in the grey areas. In the b/w copy, these products are in the area with a graph grid. Dotted arrows represent reactions that result in the breaking of C-C bonds. Also included outside the main region are the reactions of aromatics and miscellaneous reactions.

Slide63

General Organization

Left to right, compounds in the shaded regions are arranged according to the periodic table. Organolithium and Grignard reagents are under lithium and magnesium but these reagents are used elsewhere on several bold arrows for the synthesis of C-C bonds. Carbon compounds that do not contain other elements are under carbon, carbon - nitrogen (and C, N, O) compounds are under nitrogen, carbon - oxygen compounds are under oxygen and carbon - halogen (and C, O, X) compounds are under fluorine and the halogens. From top to bottom, within groups, the compounds are arranged according to the oxidation level of the compound.The oxidation level of organic compounds is somewhat of a complex concept. Even for propane, the carbons technically have different oxidation states. For the purposes of grouping compounds by oxidation level for this chart, the general guideline used has been that oxidation involves a decrease in the number of bonds to carbon from an atom less electronegative than carbon (most frequently hydrogen) and/or an increase in the number of bonds from carbon to atoms more electronegative than carbon (most frequently N, O, X). Reduction is the reverse. If two carbons change, then the sum of the changes must be considered. When water is added to a double bond, one carbon gains a hydrogen and the other an oxygen and the net oxidation level of the molecule does not change. The increase in oxidation level is indicated by the degree of darkness on the next page and in color in the online version.This organization results in five groups including: 1. alkanes (and organometallics), 2. alkenes (and alkene addition products such as alcohols, ethers and halides), aromatics and amines, 3. alkynes (and alkyne addition products such as carbonyls), 4. carboxyls

and 5. carbon dioxide and tetrahalomethane. The two crosshatched areas to the left and right of the shaded region contain products of carbon carbon bond forming reactions. These reactions are also emphasized by bold arrows. For the purposes of organizing the numbering of the reactions for this key, the reactions have been grouped according to mechanism of the first step of the reaction. Many reactions fall into more than one group. The addition of hydrogen to π bonds is usually discussed in texts along with electrophilic additions to π bonds but here the hydrogen additions have been placed in the reduction category. Reductions with hydrides such as LiAlH

4 are often grouped with nucleophilic additions but here have also been included in the reduction category. The reactions are listed in the order substitution, addition, elimination, addition-elimination, oxidation, reduction, concerted and miscellaneous. To facilitate the finding of reactions from any of the keys that follow, a roadmap grid has been included. For example, the addition of HX to an alkene is represented by reaction 30 which is in grid position B11.

Slide64

Reaction-Map as a Study Aid

At the end of a two semester course in organic chemistry, a student should be able to perform the exercises below. In addition to the exercises below, a student of organic chemistry should be able to demonstrate competency with spectroscopic, stereochemical and multistep synthetic challenges.1. For each numbered reaction, classify the reaction by mechanism (e.g., substitution, nucleophilic) and list the reagents, conditions, regioselectivity, stereoselectivity and restrictions associated with the reaction. 2. List all methods of preparing each functional group.3. List all reactions of each functional group.4. Write mechanisms for reactions: 3 (D2), 10 (B13), 19 (C13), 32 (C11), 33 (E14), 39 (J3) +28 (K2), 42 (G7), 46 (B13), 47 (C11), 62 (K13), 72 (J17), 106 (K19).The problems above should be attempted without reference to the keys but the keys can be used to help check for the correctness of answers. For the answers to question #4, reference to an organic chemistry textbook may be required.Color Chart: Key blue - alkanes, organometallics green - alkenes, aromatics, alkyl halides, alcohols, ethers, amines yellow - alkynes, carbonlys (aldehydes, ketones), oxiranes, diols, dihalides, carbonyl derivatives orange -

carboxyls (acyl halides, anhydrides, carboxylic acids, esters, amides, nitriles), haloforms red - carbon dioxide, carbon tetrahalides grey areas with bold arrows - C-C forming reactions arrows with dotted lines - s C-C bond cleavage reactions