Química Orgânica 2 · Rotas de síntese: reagentes, grupos protetores e planejamento em várias etapas
Acetonide protection of propane-1,2-diol with 2,2-dimethoxypropane
Condições: Propane-1,2-diol, 2,2-dimethoxypropane (3 equiv), TsOH·H₂O (0.02 equiv), CH₂Cl₂, 25 °C
Desenhe este problema você mesmo
Arraste dos elétrons que se movem até onde eles vão, ou toque em um e depois no outro. Cada seta é verificada; Dica ajuda quando você travar. Não precisa de conta.
O mecanismo, passo a passo
Próximo mostra as setas curvas de cada passo e as explica. Os passos escritos estão abaixo.
Ler todos os 10 passos escritos
TsOH protonates a methoxy oxygen
A lone pair on one methoxy oxygen of 2,2-dimethoxypropane takes the acidic proton of TsOH, turning that methoxy group into a leaving group (neutral methanol).
As setas curvas
- The methoxy oxygen lone pair takes the proton.
- The O–H pair stays on the sulfonate oxygen.
Methanol leaves to give an oxocarbenium ion
The other methoxy oxygen pushes a lone pair toward the central carbon as methanol departs. The cation is stabilised by the C=O⁺ π bond.
As setas curvas
- The methoxy lone pair forms the C=O⁺ π bond.
- The C–O bond breaks and methanol leaves.
Why use 2,2-dimethoxypropane?
2,2-Dimethoxypropane is a ketal of acetone, so exchanging its methoxy groups for the diol oxygens releases methanol instead of water.
The primary hydroxyl adds
The less hindered primary OH of the diol attacks the oxocarbenium carbon, and the π pair returns to the methoxy oxygen.
As setas curvas
- The hydroxyl oxygen lone pair forms the new C–O bond.
- The π pair returns to the methoxy oxygen.
Tosylate removes the proton
Tosylate takes the proton from the oxonium ion, giving a neutral mixed ketal and regenerating TsOH.
As setas curvas
- The sulfonate oxygen lone pair takes the proton.
- The O–H pair stays on the ether oxygen.
TsOH protonates the second methoxy group
The remaining methoxy oxygen is protonated so that a second methanol can leave.
As setas curvas
- The methoxy oxygen lone pair takes the proton.
- The O–H pair stays on the sulfonate oxygen.
Methanol leaves again
The diol-derived ether oxygen pushes a lone pair toward the central carbon as the second methanol leaves, giving a new oxocarbenium ion attached to the diol.
As setas curvas
- The ether oxygen lone pair forms the C=O⁺ π bond.
- The C–O bond breaks and methanol leaves.
The secondary hydroxyl closes the ring
The secondary OH on the neighbouring carbon attacks the oxocarbenium carbon. Counting the central carbon, both oxygens and the two diol carbons gives a five-membered ring, which closes quickly.
As setas curvas
- The secondary hydroxyl lone pair forms the ring C–O bond.
- The π pair returns to the ring oxygen.
Tosylate removes the last proton
Tosylate takes the proton from the ring oxonium ion, giving the neutral acetonide and regenerating TsOH.
As setas curvas
- The sulfonate oxygen lone pair takes the proton.
- The O–H pair stays on the ring oxygen.
The acetonide, 2,2,4-trimethyl-1,3-dioxolane
Both hydroxyl groups are now tied up in a five-membered cyclic ketal, stable to bases, hydrides, Grignard reagents and oxidants. Two methanol molecules are released and TsOH is regenerated. Aqueous acid removes the acetonide and returns the diol.
O que você vai praticar
Draw the acid-catalysed transfer of the isopropylidene group from 2,2-dimethoxypropane to propane-1,2-diol, through two oxocarbenium ions and with loss of two methanol molecules, that closes the five-membered acetonide ring.
Você acabou de desenhar cada seta deste problema.
Cada um dos 5349 problemas de Orgânica 1 e 2 funciona assim: feedback em cada seta, dicas quando você travar e um modo prova sem dicas. Grátis com uma conta, sem cartão.
Travou na sua própria lição?
Tire uma foto: o primeiro scan é grátis, sem cadastro
Você escaneia toda semana? Scan Standard: por cerca de problemas