p-Toluenesulfonamides
Ts-NR2, , Tosylamides
T. W. Green, P. G. M. Wuts,
Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 604-607, 744-747.
Stability
| H2O: | pH < 1, 100°C | pH = 1, RT | pH = 4, RT | pH = 9, RT | pH = 12, RT | pH > 12, 100°C |
| Bases: | LDA | NEt3, Py | t-BuOK | Others: | DCC | SOCl2 |
| Nucleophiles: | RLi | RMgX | RCuLi | Enolates | NH3, RNH2 | NaOCH3 |
| Electrophiles: | RCOCl | RCHO | CH3I | Others: | :CCl2 | Bu3SnH |
| Reduction: | H2 / Ni | H2 / Rh | Zn / HCl | Na / NH3 | LiAlH4 | NaBH4 |
| Oxidation: | KMnO4 | OsO4 | CrO3 / Py | RCOOOH | I2, Br2, Cl2 | MnO2 / CH2Cl2 |
Protection
A facile and efficient indium-catalyzed sulfonylation of amines allows the
synthesis of a wide range of sulfonamides in excellent yields. The method showed
a generality for substrates including less nucleophilic and sterically hindered
anilines, and it is also applicable for preparing sulfonic esters from sulfonyl
chlorides and alcohols.
J. Yan, J. Li, D. Cheng, Synlett, 2007,
2442-2444.
An easy and handy synthesis of sulfonamides directly from sulfonic acids or its
sodium salts is performed under microwave irradiation, has shown a good
functional group tolerance, and is high yielding.
L. De Luca, G. Giacomelli, J. Org. Chem., 2008,
73, 3967-3969.
A mild and efficient reaction of amine derived sulfonate salts in the presence
of cyanuric chloride, triethylamine as base, and anhydrous acetonitrile as
solvent at room temperature gives the corresponding sulfonamides in good to
excellent yields.
M. N. S. Rad, A. Khalafi-Nezhad, Z. Asrari, S. Behrouz, Z. Amini, M. Behrouz, Synthesis, 2009,
3983-3988.
Other Syntheses of Tos-Protected Amino Groups
A borrowing hydrogen approach using a well-defined and bench-stable Mn(I) PNP
pincer precatalyst enables an efficient manganese-catalyzed N-alkylation
of sulfonamides with benzylic and simple primary aliphatic alcohols as
alkylating agents. A diverse range of aryl and alkyl sulfonamides undergoes
mono-N-alkylation in excellent yields.
B. G. Reed-Berendt, L. C. Morrill, J. Org. Chem., 2019, 84,
3715-3724.
A biaryl phosphine ligand, t-BuXPhos and K3PO4 in
tert-amyl alcohol was found to be the optimal base-solvent combination
for a Pd-catalyzed sulfonamidation of aryl nonafluorobutanesulfonates. The
reaction conditions were tolerant of various functional groups. The only
identified limitation of this methodology is the inability of 2,6-disubstituted
aryl nonaflates to efficiently participate in the reaction.
S. Shekhar, T. B. Dunn, B. J. Kotecki, D. K. Montavon, S. C. Cullen, J. Org. Chem., 2011,
76, 4552-4553.
A mild and efficient method for the synthesis of N-arylsulfonamides in
the presence of CuCl as catalyst proceeds readily at room temperature in an open
flask using a variety of sulfonyl azides and boronic acids without any base,
ligand, or additive.
S.-Y. Moon, J. Nam, K. Rathwell, W.-S. Kim, Org. Lett., 2014,
16, 338-339.
Deprotection
The reaction of different protected alcohols, amines and amides with lithium and
a catalytic amount of naphthalene in THF at low temperature leads to their
deprotection under very mild reaction conditions, the process being in many
cases chemoselective.
E. Alonso, D. J. Ramón, M. Yus, Tetrahedron, 1997,
53, 14355-14368.
E. Alonso, D. J. Ramón, M. Yus, Tetrahedron, 1997,
53, 14355-14368.
A low-valent titanium generated in situ from Ti(O-i-Pr)4,
Me3SiCl, and Mg powder in THF reacted with a broad range of sulfonamides in a reductive bond
cleaving pathway to provide the corresponding amines, hydrocarbons and thiols.
The reagent could also cleave sulfonates to the corresponding alcohols.
N. Shohji, T. Kawaji, S. Okamoto, Org. Lett., 2011,
13, 2626-2629.
For chemoselective acidic hydrolysis of N-arylsulfonamides with
trifluoromethanesulfonic acid, a near-stoichiometric amount of the acid was
found to be sufficient to deprotect various neutral or electron-deficient N-arylsulfonamides,
whereas electron-rich substrates provided sulfonyl group migration products.
T. Javorskis, E. Orentas, J. Org. Chem.,
2017, 82, 13423-13439.
Conversion of Tos-protected Amines to other functional groups
A mild deprotection for notoriously difficult to unmask primary N-(p-toluenesulfonyl)
amides occurs at low temperature by initial activation of the nitrogen with a
trifluoroacetyl group, followed by reductive cleavage of the p-toluenesulfonyl
group with samarium diiodide.
Z. Moussa, D. Romo, Synlett, 2006,
3294-3298.
