Q6(c). NBS, KMnO₄, HIO₄; hydroboration, dehydration, OsO₄ and Pb(OAc)₄

Introduction. (i) uses allylic bromination, substitution, syn-dihydroxylation and periodate cleavage of a 1,2,3-triol. (ii) uses anti-Markovnikov hydration, acid-catalysed dehydration with rearrangement, and glycol cleavage.

(i) From cyclohexene

Scheme: Allylic bromide → allylic alcohol → 1,2,3-triol → pentanedial and formic acid.

1. A = 3-bromocyclohexene. NBS keeps a very low Br₂ concentration, so instead of addition a radical chain allylic substitution occurs: Br^ takes an allylic H (weak C–H, the radical is allylic and resonance-stabilised), and the radical takes Br from Br₂.
2. Cyclohex-2-en-1-ol. OH⁻ replaces Br (SN2, or SN1 through the allylic cation).
3. B = cyclohexane-1,2,3-triol. Cold, dilute (alkaline) KMnO₄ adds two OH groups syn through a cyclic manganate ester to the C=C.
4. C = pentanedial (glutaraldehyde) + HCOOH. HIO₄ cleaves each C–C bond between two OH-bearing carbons through a cyclic periodate ester. A 1,2,3-triol is cut twice (2 HIO₄): the two end carbons become CHO groups, still linked by the three CH₂ groups, and the middle carbon leaves as formic acid.

(ii) From but-1-ene

1. A = 1) BH₃·THF (or B₂H₆); 2) H₂O₂, NaOH. Hydroboration puts boron on the terminal carbon (steric and electronic control, syn addition), and oxidation replaces B by OH with retention: anti-Markovnikov hydration to butan-1-ol.
2. B = conc. H₂SO₄, heat (or H₃PO₄, or Al₂O₃ at high temperature). The protonated alcohol loses water with a 1,2-hydride shift to the secondary carbon (or by E2-like loss); the proton is removed to give the more substituted Zaitsev alkene, but-2-ene (mainly trans).
3. C = ethanal (acetaldehyde), 2 CH₃CHO. OsO₄ gives butane-2,3-diol (syn); Pb(OAc)₄ cleaves the 1,2-diol through a cyclic lead(IV) ester into two molecules of CH₃CHO.

Scheme: The symmetrical diol is split into two identical aldehydes.

Conclusion. (i) A = 3-bromocyclohexene, B = cyclohexane-1,2,3-triol, C = pentanedial (OHC(CH₂)₃CHO) with HCOOH. (ii) A = BH₃/THF then H₂O₂/OH⁻; B = conc. H₂SO₄/heat; C = CH₃CHO (two molecules).

Application. Glutaraldehyde is the cross-linking agent used to fix tissues and to sterilise medical equipment; periodate and lead tetra-acetate cleavage are standard tests for 1,2-diols in carbohydrate structure work.