QFL0342 Reatividade de Compostos Orgânicos (2016) Reações de redução e oxidação de compostos carbonílicos

Transcrição

1 QFL0342 Reatividade de Compostos rgânicos (2016) Reações de redução e oxidação de compostos carbonílicos

2 Reductive amination + NH 3 H 2, Ni or NaBH 3 CN CH NH 2 1 o amine + RNH 2 H 2, Ni or NaBH 3 CN CH NHR 2 o amine + R 2 NH H 2, Ni or NaBH 3 CN CH NR 2 3 o amine

3 Preparation of Amines Reductive Amination [1] Nucleophilic attack of NH 3 on the carbonyl group forms an imine. [2] Reduction of the imine forms an amine.

4 Preparation of Amines Reductive Amination The most effective reducing agent for this reaction is sodium cyanoborohydride (NaBH 3 CN). Compare to NaBH 4

5 Preparation of Amines Reductive Amination Retrosynthetic analysis

6 Preparation of Amines Reductive Amination How to prepare 2 o and 3 o amines? Which starting material would you use for it?

7 Preparation of Amines Reductive Amination How would you prepare methamphetamine?

8 Redução de Wolff-Kishner 8

9 Reações de aldeídos ou cetonas com diversos hidretos

10 Redução com hidretos metálicos s reagentes mais comuns usados em laboratório para a redução de aldeídos e cetonas são NaBH 4 ; LiAlH 4 NaH (fontes de íon hidreto H: -, um poderoso nucleófilo) Na + H H-B-H H Boro-hidreto de sódio Li + H H-Al-H H Hidreto de lítio alumínio H Íon hidreto

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12 Reduction of aldehyde with LiAlH 4 Reduction of carboxylic acid with LiAlH 4

13 LiAlH 4 reage violentamente com água, metanol e outros solventes próticos. As reduções usando LiAlH 4 são realizadas em éter dietílico ou tetra-hidrofurano (THF) anidros. LiAlH H 2 LiH + Al(H) H 2

14 Redução com LiAlH 4 4 RCR + LiAlH 4 Éter dietílico ou THF (R 2 CH) 4 Al - Li + H 2 tetralcoxi aluminato H 4 RCHR + Sais de alumínio

15 Uso de LiAlH 4 em reações de redução

16 reduzidos por NaBH 4 não são reduzidos por NaBH4 R C X R C C R R C H R C R' R C R R C NH 2 R C H haletos de acila anidridos aldeídos cetonas ésteres amidas ácidos carboxílicos reduzidos por LiAlH 4

17 Reduções com NaBH 4 podem ser realizadas em metanol aquoso, em metanol puro, ou em etanol Um mol de NaBH 4 reduz quatro mols de aldeído e cetona 4 RCH + NaBH 4 metanol (RCH 2 ) 4 B - Na + H 2 Um tetralcoxi borato 4 RCH 2 H + Boratos

18 Redução com NaBH 4 H BH 3 Na + Na + H-B-H + R-C-R' R-C-R' H H from A partir the do agente hydride reducing redutor agent H 2 H R-C-R' H from water água A partir da

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21 Quimiosseletividade nas reduções RCH=CHCR' 1. NaBH H 2 2 H RCH=CHCHR' RCH=CHCR' + H 2 Rh RCH 2 CH 2 CR'

22 DIBAL-H (hidreto de diisobutilaluminio) (Hidreto mais brando) (i-bu 2 AlH) 2 Treatment of a nitrile with a milder reducing agent such as DIBAL-H followed by water forms an aldehyde.

23 Redução de ésteres com DIBALH hidreto de di-isobutilalumínio (DIBALH) a -78 C reduz seletivamente ésteres a aldeídos a -78 C, o intermediário somente é liberado após a hidrólise ácida.

24 With DIBAL-H, nucleophilic addition of one equivalent of hydride forms an anion which is protonated with water to generate an imine. The imine is then hydrolyzed in water to form an aldehyde.

25 reduz R C H reduz lentamente não reduz via alcool ou DIBAL LiAlH 4 o C via cloretos de acila NH R C H iminas R C H aldeídos R C R' cetonas R C R ésteres R C NH 2 amidas R C H ácidos carboxílicos NaCNBH 3 NaBH 4 LiBH 4 LiAlH 4 BH 3 H R NHR R H R R R H R NR 2 R H

26 Equivalentes biológicos de hidretos metálicos NADH (hidreto biológico)

27 NAD + nicotinamida adenina dinucleotídeo (forma oxidada) NADH nicotinamida adenina dinucleotídeo reduzida

28 NAD+ NAD+ NAD+

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30 Reduções quimiosseletivas por enzimas

31 xidation of Aldehydes and Ketones Aldehydes are readily oxidized to carboxylic acid but ketones are unreactive (except under the most vigorous conditions). Aldehydes are more easily oxidized because they posses a hydrogen atom bonded to the carbonyl carbon. This hydrogen atom can be removed as a proton with the final result being the oxidation (loss of hydrogen) from the original aldehyde. Ketones have no expendable carbonyl-hydrogen bond.

32 xidation of Aldehydes and Ketones Many oxidizing agents will convert aldehydes to carboxylic acids. Some of these are Jones reagent, hot nitric acid and KMn 4. CH 3 (CH 2 ) 4 C H Jones CH 3 (CH 2 ) 4 C H ne drawback to the Jones reagent is that it is acidic. Many sensitive aldehydes would undergo acid - catalyzed decomposition before oxidation if Jones reagent was used

33 xidation of Alcohols and aldehydes with cromic acid alcohol Ester chromate aldehyde gem-diol Carboxylic acid

34 A Milder xidizing Agent For acid sensitive molecules a milder oxidizing agent such as the silver ion (Ag + ) may be used. A dilute ammonia solution of silver oxide, Ag 2, (Tollens reagent) oxidizes aldehydes in high yield without harming carbon-carbon double bonds or other functional groups.

35 xidizing Agents in rganic Chemistry N H Cr 3 Cl Cr 3 /H 2 S 4 H 2 Cr 4 Pyridinium chlorochromate (PCC) Chromic Acid (Jones Reagent) PCC Generally a Mild xidant (1 Alcohol Aldehyde) Jones Reagent Harsher xidant (1 Alcohol Carboxylic Acid) Alcohol ften Dissolved in Acetone While Jones Reagent Added

36 General xidizing Agent Selection Just as in Reductions, xidation Products Depend on Reagent Generally Don t xidize 3 Alcohols (No Texas Carbons) MeH 1 Alcohol 2 Alcohol 3 Alcohol PCC H 2 C= Aldehyde Ketone Cr 6+ H 2 S 4 HC 2 H Carboxylic Acid Ketone No Reaction No Reaction PCC Good For Aldehydes From Primary Alchols Cr 6+ /H 2 S 4 Reagents, KMN 4 Primary Carboxylic Acids Use What You Like For Most Ketones