Open KlementineJBS opened 4 months ago
Identifier | Link | Solvent | Yield | Other |
---|---|---|---|---|
44-1 | #159 | DMF | contaminated with DIAD | SM = KBS49-1c F7 |
44-2 | #188 | DMF | 52% fully deprotected | SM = KBS49-2c F75-120 |
53-1 | #190 | DMF | 20% purified | SM = KBS48-2b 36-110 |
53-2 | #193 | DMF | - | SM = pooled from KBS48-1/2 |
52-1 | #191 | DMF | - | SM = KBS51-1 F37-89 |
See #188
1H NMR (300 MHz, Chloroform-d) δ 8.07 – 7.90 (m, 4H), 7.86 (s, 2H), 7.68 – 7.45 (m, 10H), 4.10 – 4.05 (m, 4H), 2.76 (t, J = 7.2 Hz, 4H), 1.75 (s, 4H), 1.35 (s, 8H).
Could use a "stronger" thiol i.e. one with a better stabilised S-.
Obvious solutions are mercaptothanol, thiophenol, etc but these are quite hazardous. 1-decanethiol is safer but not on hand.
2,2'-(Ethylenedioxy)diethanethiol, 4-Methoxythiophenol, 1-dodecanethiol and thioanisole are reasonably safe and could be borrowed from another lab.
NMR of 2,2′-(Ethylenedioxy)diethanethiol suggests it is pure
1H NMR (300 MHz, Chloroform-d) δ 3.68 – 3.58 (m, 4H), 2.71 (dt, J = 8.2, 6.4 Hz, 2H), 1.60 (t, J = 8.2 Hz, 1H).
Nosyl deprotection is facilely achieved with thiophenol but this is discouraged due to its hazards and foul smell. Matoba et al discuss odorless alternatives and while they found p-mercaptobenzoic acid to be the best reagent, o-mercaptobenzoic acid (thiosalicylic aicd) is similarly effective and easy to remove. It requires slightly longer reaction times etc but is considerably cheaper and already owned by the group. Both can be used with K2CO3.
Proceeds via formation of Meisenheimer complex (SnAR).
Link to HIRAC
KBS44 Nosyl deprotection of linear amines.docx
Reaction scheme