Isotopically labeled chemically stable reagents and process for the synthesis thereof
View Patent ↗A radioisotope labeled reagent includes a compound having the general formula (I), L-( a C b H 2 ) n a C b H 3 (I) where a in each occurrence independently is a carbon mass number between 11 and 14 inclusive, b in each occurrence independently is a hydrogen mass number between 1 and 3 inclusive, such that a in each occurrence is not 12 simultaneously with b in each occurrence being 1; L is a leaving group R 1 SO 2 —O—, R 1 —S—, 12 C 1 H 3 ( 12 C 3 H 2 ) n —S—R 1 C(O)O—, NC—, (R 1 ) 3 P—, XMg- and Li—, where n is an integer between 0 and 3 inclusive, where X is chloro, bromo or iodine, where R 1 is H, aryl, a substituent containing aryl, C 1 -C 20 alkyl, a substituent containing C 1 -C 20 alkyl, C 2 -C 20 alkenyl, a substitute containing C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, and a substitute containing C 2 -C 20 alkynyl with the proviso that when n is 0, a is 13 and b is 2 and R 1 in R 1 —S is not aryl.
1. An isotopically labeled reagent comprising:
a compound having a formula
L-( a C b H 2 ) n a C b H 3 (I)
where a in each occurrence is independently a carbon atomic mass number of 11, 13 or 14, where b in every occurrence is a hydrogen atomic mass number of 1, 2 or 3, where L is a leaving group R 1 C(O)O—, where n is 0, where R 1 is a substituent containing aryl, C 3 -C 20 alkyl, a substituent containing C 3 -C 20 alkyl, C 4 -C 20 alkenyl, a substituent containing C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, or a substituent containing C 2 -C 20 alkynyl;
with the proviso that when R 1 is a substituent containing aryl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 1 -C 6 alkyl;
with the proviso that when R 1 is a substituent containing C 3 alkyl, that said substituent is selected from the group consisting of: cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 1 -C 6 alkyl;
with the proviso that when R 1 is a substituent containing C 2 alkenyl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is a C 1 -C 6 alkyl; with the further proviso that when said substituent is a substituent containing phenyl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 1 -C 6 alkyl;
with the proviso that when R 1 is a substituent containing C 11 alkenyl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 1 -C 6 alkyl;
with the proviso that when R 1 is a substituent containing C 4 alkenyl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is a C 1 -C 6 alkyl;
with the proviso that when R 1 is a substituent containing C 6 alkenyl that said substituent is selected from the group consisting of: amino; cycloalkyl; nitro; halo; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 1 -C 6 alkyl;
with the proviso that when R 1 is a substituent containing C 5 alkenyl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of hydrogen, C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 1 -C 6 alkyl
with the proviso that when R 1 is a substituent containing C 4 alkyl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 2 -C 6 alkyl;
with the proviso that when R 1 is a substituent containing C 8 alkyl that said substituent is selected from the group consisting of: amino; cycloalkyl; halo; nitro; cyano; —OR 2 wherein R 2 is selected from the group consisting of C 2 -C 6 alkyl, C 5 or C 6 cycloalkyl, a heterocycloalkyl, and a substituent containing phenyl; acyl; and —COOR 3 wherein R 3 is hydrogen or C 2 -C 6 alkyl.
2. The reagent of claim 1 wherein R 1 is said substituent containing aryl.
3. The reagent of claim 2 wherein said substituent further comprises a dye moiety.
4. The reagent of claim 3 wherein said dye moiety is selected from the group consisting of: cyanine and rhodamine.
5. The reagent of claim 1 wherein said leaving group is R 1 C(O)O—.
6. The reagent of claim 5 wherein R 1 is C 3 -C 6 alkyl.
7. The reagent of claim 1 wherein said leaving group is (C 6 H 5 )3P—.
8. A process for preparing a compound of Formula I according to claim 1 comprising the step of reacting a C b H 3 ( a C b H 2 ) n X with [L] y− M p Z+ where L is a leaving group R 1 C(O)O—, where M is a metal ion or onium ion, Z+ is a cationic valency of M, Y− is an anionic valency of L, P is the absolute value of the ionic valency divided by the cationic valency; and where the reaction occurs under anhydrous conditions in an aprotic solvent.
9. The process of claim 8 wherein a a C b H 3 ( a C b H 2 ) n X is reacted with [L] y− M p Z+ reagent.
10. The process of claim 8 wherein the step of reacting occurs with heating to a temperature less than or equal to a boiling temperature for said aprotic solvent.
11. The process of claim 8 wherein a C b H 3 ( a C b H 2 ) n X is reacted with 12 C 3 H 3 I.
12. A method of isotopically alkylating a target molecule comprising mixing under reaction conditions with said target molecule an effective amount of a compound of Formula I according to claim 1 .
13. The method of claim 12 wherein said target molecule is a nucleophile.
14. The method of claim 12 wherein said target molecule is a metallic salt of an organic anion.
15. The method of claim 12 wherein said target molecule is a tertiary amine.
16. The method of claim 12 wherein said compound of Formula I is XMg-, where n is an integer between 0 and 3 inclusive, where X is chloro, bromo or iodine, where R 1 is H, aryl, a substituent containing aryl, C 1 -C 20 alkyl, a substituent containing C 1 -C 20 alkyl, C 2 -C 20 alkenyl, a substituent containing C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, and a substitute containing C 2 -C 20 alkynyl with the proviso that when n is 0, a is 13 and b is 2 and R 1 in R 1 —S is not aryl and said target molecule is a carboxylic acid, ester or amide.