Synthesis of non-symmetrical sulfamides using burgess-type reagents
A practical and high-yielding method for the efficient, one-step synthesis of diverse classes of N,N′-differentiated sulfamides employs a wide range of amino alcohols and simple amines using Burgess-type reagents. This methodology extends the application and availability of sulfamides within the fields of chemical biology, medicinal chemistry, asymmetric synthesis, and supramolecular chemistry.
1. A process for the synthesizing a mono-protected, non-symmetrical cyclic sulfamide III from an amino alcohol I and Burgess reagent II represented by the following structures:
the process comprising the following steps:
Step A: contacting a solution of the amino alcohol I in a non-reactive solvent with a quantity of the Burgess reagent II for producing sulfamide III; then, after consuming amino alcohol I
Step B: neutralizing the reaction of said Step A by dilution with a non-reactive solvent and treatment with an aqueous solution; and then
Step C: isolating sulfamide III;
wherein:
X is absent or is a diradical selected from the group consisting of the following structures:
R 1 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl, or is a diradical forming a ring with R 2 ;
R 2 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl, or is a diradical forming a ring with R 1 or R 3 or R 4 , or is a diradical forming a part of an aromatic ring with R 5 ;
R 3 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl, or is a diradical forming a ring with R 1 or R 2 or R 5 or is a diradical forming half of a π-bond with R 6 ;
R 4 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, and benzyl or is a diradical forming a ring with R 2 or with R 5 ;
R 5 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl, or is a diradical forming a ring with R 1 or R 2 or R 6 or is a diradical forming part of an aromatic ring with R 3 ;
R 6 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl, or is a diradical forming a ring with R 1 or R 2 or R 5 or is a diradical forming half of a π-bond as part of an aromatic ring with R 3 ;
R 7 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl;
Y is a radical selected from the group consisting of —CH 3 , —CH 2 Ph and —CH 2 CH═CH 2 ;
with the following proviso:
if R 2 and R 5 are part of an aromatic ring; then R 3 and R 6 make up a full π-bond;
if X is absent, then R 3 cannot be half of a π-bond and R 2 is not part of an aromatic ring.
2. A process according to claim 1 where the quantity of Burgess reagent II is 2.5 equivalents.
3. A process according to claim 2 where X is absent.
4. A process according to claim 2 where X is a diradical with the following structure:
5. A process according to claim 2 where X is a diradical with the following structure:
6. A process for synthesizing a mono-protected, non-symmetrical sulfamide V from an amine IV and Burgess reagent II represented by the following structures:
the process comprising the following steps:
Step A: contacting a solution of the amine IV with a quantity of Burgess reagent II for producing sulfamide V; then
Step B: neutralizing the reaction of said Step A by dilution with a non-reactive solvent and treatment with an aqueous solution; and then
Step C: isolating the sulfamide V;
wherein:
R 1 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl, or a diradical forming a ring with R 2 ;
R 2 is a radical selected from the group consisting of hydrogen, C 1 –C 6 alkyl, aryl, heteroaryl, alkylaryl, and benzyl, or a diradical forming a ring with R 1 ; and
Y is a radical selected from the group consisting of —CH 3 , —CH 2 Ph and —CH 2 CH═CH 2 .
7. A process according to claim 6 wherein the quantity of Burgess reagent II is 1.25 equivalents.