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Reactions >> Protecting Groups >> Stability

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 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.