4. COMPOUNDS RELATED TO ARYLSULFONIC ACIDS
The title for this section aptly illustrates the almost arbitrary criteria used to
group potential drugs in this chapter. The few entries in this section com-
prise an interesting contrast to a full sizeable chapter that was devoted to
sulfonamide related drugs in Volume 1 of this series. Arylsulfonic acid
derived moieties formed an essential part of the pharmacophore in virtually
every one of the 40 odd antibacterial, diuretic, and antidiabetic agents
described in that chapter. In the case at hand, by way of contrast, this
functionality is no more than a convenient handle by which to coral a
group of compounds with otherwise widely divergent structures, as well
as biological activities.
A benzene ring that contains two sulfonic acid groups, as well as a
nitrone, is currently being investigated as a treatment for stroke. The free
radical scavenging properties of this compound,disufenton( 89 ), will, it
is hoped, translate into neuroprotective action on brain tissue when admi-
nistered during the first 6 h after a cerebral stroke. The synthesis of this
compound starts with the preparation of the highly substituted hydroxyl-
amine ( 86 ). Thus, reaction of benzaldehyde withtert-butylamine leads to
imine 83. Oxidation of intermediate 83 with m-perchlorobenzoic acid
(MCPBA) gives the oxazirane ( 84 ); this rearranges to the corresponding
nitrone ( 85 ) on heating. Hydrogen sulfide then serves to reduce that inter-
mediate to the requisite hydroxylamine ( 86 ). In a somewhat unusual reac-
tion, treatment of 2,4-dichlorobenzaldyde with sodium sulfite at elevated
temperature leads to displacement of each of the halogens by sulfur to
give the disulfonic acid ( 88 ) as its sodium salt. This SN2-like reaction is
probably facilitated by the lowered electron density at the 2 and 4 positions
of the starting benzaldehyde ( 87 ). Reaction of the products ( 88 ) with the
intermediate ( 86 ), leads to formation of the nitrone ( 89 ) by hydroxylamine
interchange. Thus 89 is obtained.^15
C 6 H 5 CH=O
82H 2 NC(CH 3 ) (^3) C 6 H 5
83
NC(CH 3 ) 3 C 6 H 5
84
MCPBA NC(CH 3 ) 3
O
86
NC(CH 3 ) 3
OH
Heat C^6 H^5
85
NC(CH 3 ) 3
CH=O
Cl
Cl
87
Na 2 SO 3 CH=O
SO 2 Na
NaO 3 S
88
C 6 H (^5) SO 2 Na
NaO 3 S
89
NC(CHO 3 ) 3
O
H 2 S
- COMPOUNDS RELATED TO ARYLSULFONIC ACIDS 53