A. Complete
the following Reactions:
1. Acid chloride + 3o amine -----> No reaction
2. Nitrite ion with mineral acid froms nitrosonium ion which substitutes on the highly
Activated phenol ring.
3. Aldol: Acetone with H- (a strong base) forms enolate which reacts with unreacted acetone.
4. 1o alkyl amine with nitreosonium ion yields 1 carbocation (very unstable).
5. Halide + Mg forms Grignard reagent
6. Sandmeyer reaction, diazonium ion with copper (I) halide
7. Acid catalyzed aldol reaction of aldehyde with a-hydrogens.
8. Phenol is a strong enough acid to react completrely with a strong base.
9. 1o amine is moderate base, forming salt with strongf acid.
10. Ketone (with a-hydrogens) with base yields enolate which reacts with bromine.
11. Seeing an aryl -NH2
group (not a good leaver) replaced by -Cl implies
diazotization.
Use NO+ , then CuCl. See # 6.
12. Benzene diazonium ion reacts with BF4- to fluorinate the ring.
13. Due to intense activation by -OH, phenol reacts with bromine water at the para-
and both ortho- positions.
14. Check for missing carbonyl type oxygen. Acid catalyzed ALDOL reaction.
of ketone having -hydrogens. Dehydration likely due to conjugation.
15. Alkyl Azides are reduced to amines by LAH.
16. An aryl
halide, activated by electron withdrawing groups in the ortho-
and para- positions,
is subject to nucleophilic attack by methoxide ion, -OCH3
.
17. A ketone with a-hydrogens
is converted by "super base" into the enolate which
is then involved
in an SN2-like reaction on the selenium.
18. Nitrite ion + strong acid yield nitrosonium ion which diazotizes the -NH2 .
19. Kolbe reaction: forms salicylic acid.
20. Sandmeyer with CuBr. See #6 and #11.
21. Claisen: Methoxide ion abstracts a-hydrogen from methyl propionate forming
enolate which attacks unreacted ester. Presence of leaving group leads to
substitution on carbonyl.
22. Phenol with base forms phenoxide ion which undergoes SN2 with 1o halide.
23. Alkyl halide with 2o amine yields 3o amine by SN2.
24. Ester with "super base" forms enolate which acts as nucleophile on alkyl halide:
DIRECT ALKYLATION.
25. Grignard forms; being a very strong base it reacts with weak acid D2O.
26. Default aryl diazonium ion reaction. F+ reacts with H2O.
27. "Alcohols" + anhydrides yield esters. Here phenol shows alcohol-like behavior.
28. "Malonic ester" with its double hydrogens will undergo direct alkylation with
alkoxide base.
29. 1o amine with an acid chloride yields N-substituted amides.
30. Amides are reduced by LAH to amines.
31. The carbonyl-like Nitrile group has a-hydrogens which are abstracted by
"super base" forming enolates quantitatively, enabling direct alkylation.
32. Sandmeyer : See #'s 6, 11, & 20.
33. Gabriel synthesis of amine.
34. Anhydride + 1o amine yield N-substituted amide.
35. "Acetoacetic Ester" undergoes direct alkylation with alkoxide ion. See # 28.
36. Reimer-Tiemann reaction: Forms dichloro-carbene which reacts with activated
phenoxide ring, followed by hydrolysis to aldehyde.
37. Benzene diazonium ion forms benzene with H3PO2.
38. A -Se-F group "a" to a carbonyl group is easily oxidized to conjugated double bond.
39. Note: HNO3 not HNO2. Chlorine is o-, p-director although deactivator.
40. N-Substituted aromatic amines cannot form diazonium ions.
2o amines form Nitrosamines.
41. Phenoxide ion acts as nucleophile on CH3Cl. Note: It's not CHCl3 !
42. Without a-hydrogens, benzaldehyde will only undergo the slow Cannizzaro reaction
with hydroxide. When acetone is added dropwise, its enolate forms which reacts with the
more abundant benzaldehyde carbonyl. Crossed Aldol
43. Iodide ion, although present in lower concentration, is a powerful enough nucleophile
to compete successfully with the more abundant water for +.
44. Direct aryl chlorination. Methyl group is activating o-, p-director.
45. Crossed Claisen. Without a-hydrogens, methyl benzoate will show no net reaction with
methoxide ion. When methyl valerate is added dropwise, its enolate forms and reacts with the
more abundant methyl benzoate carbonyl.
46. NO+ does not react with 3o amines but it can act as an electrophile toward a
highly activated ring.
47. Under these very mild conditions phenol can be MONO-brominated.
48. The benzene diazonium ion is an electrophile and will react with highly activated rings.
49. Crossed
Claisen. Without a-hydrogens,
methyl benzoate will show no net reaction with
methoxide ion. When acetone is added dropwise, its enolate forms
and reacts with
the more abundant methyl benzoate carbonyl. Since the carbonyl attacked
has a
leaving group this is a Claisen-type reaction.
50. Reductive Amination: Converts aldehydes or ketone to amines.
51. (Sulfonic) acid chlorides react with 1o or 2o amines to form N-substituted amides.
52. Crossed
Aldol: Without a-hydrogens,
benzaldehyde will show no net reaction with
methoxide ion. When methyl butyrate is added dropwise, its enolate forms
and reacts
with the more abundant benzaldehyde carbonyl. Since the carbonyl attacked
has
no good leaving group this is a Aldol-type reaction.
53. Benzyne (Elimination/Addition) mechanism: (Inductive) electron withdrawing
properties of -OCH3 direct orientation of substitution.
54. Hoffmann Elimination: With quaternary ammonium hydroxides the less stable
(less substituted) alkene forms when possible.
55. Direct alkylation of amine. SN2. Polysubstitution possible.
56. Hydrolysis and decarboxylation of alkylated malonic ester.
57. LAH reduces nitriles to 1 amines.
58. OMIT: Same as # 13.
59. "Fremy's Salt" or (KSO3)2NO oxidizes phenol (and aniline) to quinone.
60. Fries Rearrangement
61. Direct alkylation of cyclic ester with
"super base" .
B. OUTLINE THE FOLLOWING SYNTHESES:
1. Hint: Remember, phenol is extremely active toward electrophiles.
2. Hint: Aceto-acetic ester can be directly alkylated twice.