Chapter 23 Amines Review of Concepts azide synthesis synthesis reductive amination sodium cyanoborohydride Hofmann elimination

Size: px

Start display at page:

Download "Chapter 23 Amines Review of Concepts azide synthesis synthesis reductive amination sodium cyanoborohydride Hofmann elimination"

Rosamond Clarke
5 years ago
Views:

1 Chapter 23 Amines eview of Concepts Fill in the blanks below. To verify that your answers are correct, look in your textbook at the end of Chapter 23. Each of the sentences below appears verbatim in the section entitled eview of Concepts and Vocabulary. Amines are,, or, depending on the number of groups attached to the nitrogen atom. The lone pair on the nitrogen atom of an amine can function as a or. The basicity of an amine can be quantified by measuring the pk a of the corresponding. Aryl amines are less basic than alkyl amines, because the lone pair is. Pyridine is a stronger base than pyrrole, because the lone pair in pyrrole participates in. An amine moiety exists primarily as at physiological p. The azide synthesis involves treating an with sodium azide, followed by. The synthesis generates primary amines upon treatment of potassium phthalimide with an alkyl halide, followed by hydrolysis or reaction with 2 4. Amines can be prepared via reductive amination, in which a ketone or aldehyde is converted into an imine in the presence of a agent, such as sodium cyanoborohydride (ab 3 C). Amines react with acyl halides to produce. In the ofmann elimination, and amino group is converted into a better leaving group which is expelled in an process to form an. Primary amines react with a nitrosonium ion to yield a salt in a process called diazotization. Sandmeyer reactions utilize copper salts (CuX), enabling the installation of a halogen or a group. In the Schiemann reaction, an aryl diazonium salt is converted into a fluorobenzene by treatment with. Aryldiazonium salts react with activated aromatic rings in a process called coupling, to produce colored compounds called dyes. A cycle is a ring that contains atoms of more than one element. Pyrrole undergoes electrophilic aromatic substitution reactions, which occur primarily at C.

2 604 CAPTE 23 eview of Skills Fill in the blanks and empty boxes below. To verify that your answers are correct, look in your textbook at the end of Chapter 23. The answers appear in the section entitled SkillBuilder eview aming an Amine PVIDE A SYSTEMATIC AME F TE FLLWIG CMPUD 1) IDETIFY TE PAET 2) IDETIFY AD AME SUBSTITUETS 3) ASSIG LCATS T EAC SUBSTITUET 4) ALPABETIZE 5) ASSIG CFIGUATI 23.2 Preparing a Primary Amine via the Gabriel eaction IDETIFY EAGETS TAT WILL ACIEVE TE FLLWIG TASFMATI: 1) 2) 3) Preparing an Amine via a eductive Amination IDETIFY EAGETS TAT WILL ACIEVE EAC F TE FLLWIG TASFMATIS: C 3 2

3 CAPTE Synthesis Strategies IDETIFY TE EACTAT TAT IS USED AS A UCLEPILE I EAC F TE TEE PCESSES SW BELW: GABIEL SYTESIS AZIDE SYTESIS EDUCTIVE AMIATI QUATEAY AMMIUM I EDUCTIVE AMIATI EDUCTIVE AMIATI ALKYLATI PIMAY AMIE SECDAY AMIE TETIAY AMIE 23.5 Predicting the Product of a ofmann Elimination PEDICT TE MAJ PDUCT F TE FLLWIG EACTI: 2 1) excess C3 I 2) Ag 2, 2, heat 23.6 Determining the eactants for Preparing an Azo Dye IDETIFY EAGETS TAT WILL ACIEVE TE FLLWIG TASFMATI: Me 1) 2) S 3 Me

4 606 CAPTE 23 eview of eactions Identify the reagents necessary to achieve each of the following transformations. To verify that your answers are correct, look in your textbook at the end of Chapter 23. The answers appear in the section entitled eview of eactions. Preparation of Amines C X

5 CAPTE eactions of Amines 2 eactions of Aryldiazonium Salts I C F

6 608 CAPTE 23 eactions of itrogen eterocycles Solutions ,3-dimethyl-1-butanamine cyclopentylamine,-dimethylcyclopentylamine d) triethylamine e) (1S,3)-3-isopropylcyclohexanamine f) (1S, 3S)-3-aminocyclohexanol C 3 d) C3 e) trimethylamine ethyl methyl amine propylamine isopropylamine Increasing boiling point 2

7 CAPTE o. This compound has eight carbon atoms and only one functional group. Yes. Yes d) Increasing Basicity In the reactant, the lone pair of the amino group is delocalized via resonance. In the product, the lone pair of the amino group is localized. 2 2 Pt C ) ac 2) LA 3) 2 1) S 2, py 2) 3 2 3) LA 4) 2

8 610 CAPTE 23 1) ac 2) LA 3) 2 2 1) S 2, py 2) 3 3) LA 4) 2 1) ac 2) LA 3) 2 2 1) S 2, py 2) 3 3) LA 4) This compound cannot be prepared from an alkyl halide or a carboxylic acid, using the methods described in this section, because there are two methyl groups at the alpha position (the carbon atom connected to the amino group). These two methyl groups cannot be installed with either of the synthetic methods above, because both methods produce an amine with two alpha protons ) K 2) 3) ) K 2) Ph Ph 3) 3 + 2

9 CAPTE ) K 2) 2 3) 3 + 1) K d) 2) 3) ) K 1) 2, hv 2 2) t-buk 3), 2) 3 + 1) K 1) excess LA 2 2) 2 2) 3 + 3) P [ + ], ab 3 C 2 [ + ], ab 3 C 2

10 612 CAPTE 23 [ + ], ab 3 C [ + ], ab 3 C [ + ], ab 3 C [ + ], ab 3 C 2 d) [ + ], ab 3 C [ + ], ab 3 C

11 CAPTE e) [ + ], ab 3 C [ + ], ab 3 C [ + ], ab 3 C C The last step of reductive amination is the reduction of a C= bond. That step introduces a proton on the alpha position (the carbon atom that is connected to the nitrogen atom in the product): C As a result, the product of a reductive amination must have at least one proton at the alpha position. In the case of tri-tert-butyl amine, there are three alpha positions, and none of them bears a proton. Each of the alpha positions has three alkyl groups and no protons. C Therefore, this compound cannot be made with a reductive amination ) 2, hv 2) aet 1) 3 2) DMS [ + ] ab 3 C (C 3 ) 2

12 614 CAPTE [ + ], ab 3 C [ + ], ab 3 C 3 2 [ + ], ab 3 C 3 2 [ + ], ab 3 C 3 2 [ + ], ab 3 C [ + ], ab 3 C d) [ + ], ab 3 C [ + ], ab 3 C 3 2 e) [ + ], ab 3 C [ + ], ab 3 C 3 2 [ + ], ab 3 C

13 CAPTE f) [ + ], ab 3 C 3 2 [ + ], ab 3 C [ + ], ab 3 C The first alkyl group is installed via a Gabriel synthesis, and the remaining alkyl groups are installed via reductive amination processes. For most of the following syntheses, there is a choice regarding which group to attach via the initial Gabriel synthesis. In such cases, the least sterically hindered group is chosen (the group whose installation involves the least hindered alkyl halide): K K 1) 1) 2) 3 + 2) [ + ], ab 3 C K 1) C 3 2) 3 + C 3 2 [ + ], ab 3 C [ + ], ab 3 C

14 616 CAPTE 23 d) K 1) [ + ], ab 3 C e) K 2) 3 + 1) 2) [ + ], ab 3 C [ + ], ab 3 C f) K 1) 2) 3 + Et 2 [ + ], ab 3 C [ + ], ab 3 C The first alkyl group is installed via an azide synthesis, and the remaining alkyl groups are installed via reductive amination processes. For most of the following syntheses, there is a choice regarding which group to attach via the initial azide synthesis. In such cases, the least sterically hindered group is chosen (the group whose installation involves the least hindered alkyl halide): 1) a 3 2) 2, Pt 2 [ + ], ab 3 C

15 CAPTE ) a 3 2) 2, Pt 2 1) a 3 C 3 2) 2, Pt C 3 2 [ + ], ab 3 C [ + ], ab 3 C d) 1) a 3 [ + ], ab 3 C 2) 2, Pt 2 e) 1) a 3 2) 2, Pt 2 [ + ], ab 3 C [ + ], ab 3 C

16 618 CAPTE 23 f) 1) a 3 2) 2, Pt 2 [ + ], ab 3 C [ + ], ab 3 C ) 3 2) DMS [ + ], xs ab 3 C a 2 S 4 or a Zn or 3 +

17 CAPTE ) excess 3 2) LA 3) 2 S ) excess C 3 I 2) Ag 2, 2, heat 2 1) excess C 3 I 2) Ag 2, 2, heat 1) excess C 3 I 2) Ag 2, 2, heat ) ac 2 1) excess C 3 I 2) LA 3) 2 2) Ag 2, 2 heat Compound A 1) excess C 3 I 2) Ag 2, 2 heat 1) 3 2) DMS +

18 620 CAPTE ) excess C 3 I 2) Ag 2, 2, heat d) ) 2 2) (C 3 ) 2 C, 2 1) a 2, 2) CuC C Al 3 3) ) 2, Fe 3 1) a 2, 2) Fe, 3 + 2) Cu 3 2 Al 3 2 S 4, Zn[g] heat 1) a 2, 2) 2, heat 2

19 CAPTE d) 1) Fe, 3 + 1) (C 3 ) 3, Al 3 2) a 2, 2 2) 3, 2 S 4 3) CuC 4) 3 + e) 1) 2, Al 3 2) 3, 2 S 4 1) Fe, F 2) a 2, 3) BF 4 f) 1) a 2 2) a 2, 3) Cu S 2 S 3 1) a 2, 2) 2 3 S S ) a 2, 2 2) 2 2 1) a 2, 2 2)

20 622 CAPTE ) Fuming 2 S 4 2 Al 3 1) 3, 2 S 4 2) Fe, 3 + 2) 3, 2 S 4 3) Dilute 2 S 4 Fe, ) 2) 3, 2 S 4 3) 3 + 4) a 2, Me

21 CAPTE Attack at either C2 or C4 generates an intermediate that exhibits a resonance structure with a nitrogen atom that lacks an octet (highlighted below). Attack at C3 generates a more stable intermediate: E C2 ATTACK E E E E C3 ATTACK E E E C4 ATTACK E E E E , 2 S C The second compound will have an - stretching signal between 3300 and 3500 cm -1. The first compound will not have such a signal. When treated with, the first compound will be protonated to form an ammonium salt that will produce an I signal between 2200 and 3000 cm -1. The second compound is not an amine and will not exhibit the same behavior The 1 M spectrum of the first compound will have a singlet resulting from the - methyl group. 1 M spectrum of the second compound will not have any singlets. The 1 M spectrum of the first compound will have six signals, while the 1 M spectrum of the second compound will have only three signals.

22 624 CAPTE secondary primary The lone pair that is farthest away from the rings is the most basic, because its lone pair is localized. The lone pair of the other nitrogen atom is delocalized via resonance. 3 C C d)

23 CAPTE nly one of the nitrogen atoms has a localized lone pair (highlighted in the following structure). The other two nitrogen atoms have delocalized lone pairs two two one ,2,3,3-tetramethyl-1-hexanamine (S)-4-amino-2,2-dimethylcyclohexanone dicyclobutylmethylamine d) 3-bromo-2,6-dimethylaniline e),-dimethyl-3-propylaniline f) 2,5-diethyl--methyl pyrrole ethyldimethylamine diethylamine methylpropylamine isopropylmethylamine 1-butanamine 2-butanamine 2-methyl- 1-propanamine 2-methyl- 2-propanamine one of these compounds are chiral. dimethylpropylamine isopropyldimethylamine diethylmethylamine

24 626 CAPTE Base Acid + + Base Acid C 3 3 C C 3 I C d) e) ) P 3 2) a 3 3) 2, Pt 2 1) P 3 2) ac 2 3) LA 4) 2 1) P 3 2) t-buk 2 3) 3 4) DMS 5) [ + ], ab 3 C, 3

25 CAPTE ) a 3 2) 2, Pt 2 1) ac 2) LA 2 3) 2 1) S 2, py 2) xs 3 3) LA 4) 2 2 d) C 1) LA 2) Aziridine has significant ring strain, which would increase significantly during pyramidal inversion. This provides a significant energy barrier that prevents pyramidal inversion at room temperature A A A C 3 C B - 2

26 628 CAPTE In acidic conditions, the amino group is protonated to give an ammonium ion. The ammonium group is a powerful deactivator and meta-director The presence of the nitro group in the para position helps stabilize the conjugate base via resonance. As seen in chapter 19, this effect only occurs when the nitro group is in the ortho and para positions. The basicity of ortho-nitroaniline should be closer in value to para-nitroaniline Protonation of the oxygen atom gives a resonance stabilized cation (as seen in chapter 20). In contrast, protonation of the nitrogen atom gives a cation that is not resonance stabilized ) C 3, Al 3 1) a 3 2 2) BS, heat 2) 2, Pt [ + ], ab 3 C 1) Al 3 2) 3, 2 S 4 2 1) Fe, 3 + 2) a 2, 3) CuC 4) 3 + C

27 CAPTE C C ) excess MeI 2) Ag 2, 2, heat 1) K 2) Et 2 3) 2 2

28 630 CAPTE 23 1) ac, DMS 2) 3 +, heat 3) S 2, py 4) xs 3 2 d) ) 3 / 2 S 4 2) Fe, 3 + 3) a 2, 4) CuC C [ + ] 1) excess MeI ab 3 C (C 3 ) 2 2) Ag 2, 2, heat 1) 3 2) DMS 2 2 [ + ] xs ab 3 C xs 3 C C The conjugate base of pyrrole is highly stabilized because it is an aromatic anion and it is resonance stabilized, spreading the negative charge over all five atoms of the ring:

29 CAPTE [ + ], ab 3 C [ + ], ab 3 C Fe 3 +

30 632 CAPTE [ + ] ab 3 C C 1) xs LA 2 2) 2 d) 1) xs LA 2) F C d) e) [ 2 S 4 ] ab 3 C a 2, ) Mg Fe 3 [ + ] 2) ab 3 C 3) 2 4) PCC, C 2 2

31 CAPTE ) 3, 2 S 4 2) Fe, 3 + xs 2 1) a 2, 2) CuC 3) 3 + a 2, 3 2 Fe 3 1) Mg 2) C 2 3) ) S 2 d) 1) 2 Al 3 1) 2, Al 3 2) 3, 2 S 4 3), Zn[g], heat a 2 2) a 2,

32 634 CAPTE The I data indicates that we are looking for structures that lack an - bond (i.e tertiary amines): The compound is a tertiary amine with the appropriate symmetry that provides for only three signals: or Coniine 1) excess C 3 I 2) Ag 2, 2

33 CAPTE ) C 3 C 2 C, Al 3 2) MeMg 1) conc. 2 S 4, heat 3) 2 2) MCPBA 3 [ + ], ab 3 C C ) 2, Al 3 2) a, heat 3) EtI 1) 3, 2 S 4 2) Fe, 3 + 3) heat benzyne (see Chapter 19) C 2

34 636 CAPTE a, 3 1) 3 [ + ] C 3 2) DMS ab 3 C ) 2, hv 2) aet 3) 3 4) DMS [ + ] ab 3 C C 3 2

35 CAPTE a a

36 638 CAPTE Protonation of the nitrogen highlighted below results in a cation that is highly resonance stabilized. Protonation of either of the other nitrogen atoms would not result in a resonance stabilized cation: 2 2 A

Chapter 22: Amines. Organic derivatives of ammonia, NH 3. Nitrogen atom have a lone pair of electrons, making the amine both basic and nucleophilic

Chapter 22: Amines. Organic derivatives of ammonia, NH 3. Nitrogen atom have a lone pair of electrons, making the amine both basic and nucleophilic hapter 22: Amines. rganic derivatives of ammonia, 3. itrogen atom have a lone pair of electrons, making the amine both basic and nucleophilic 22.1: Amines omenclature. (please read) sp 3 Amines are classified