KBS44, 52, 53 (Nosyl deprotection) - master page

[KlementineJBS]

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

[KlementineJBS]

Attempts

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

[KlementineJBS]

Characterisation

H NMR

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).

[KlementineJBS]

Ideas

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.

[KlementineJBS]

Thiols

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).

thiol.pdf
nmr300_20240419_KBS thiol_1.zip