LOW TOXICITY NMP SUBSTITUTES AND USES THEREOF

1 . A compound of Formula I, Formula II, Formula III, or Formula IV:

wherein:

X is O or CR 33 R 34 ;

R 1 , R 8 , R 9 , R 17 , and R 26 are each independently —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , or —CH(CH 3 ) 2 ;

R 2 , R 3 , R 10 , R 11 , R 14 , and R 15 are each independently —H, —CH 3 , or —CH 2 CH 3 ;

R 6 and R 7 are each independently absent, —H, —CH 3 , —CH 2 CH 3 , —CN, —C(O)N(CH 3 ) 2 , —CH 2 C(O)N(CH 3 ) 2 , —C(O)N(CH 2 CH 3 ) 2 , —CH 2 C(O)N(CH 2 CH 3 ) 2 , —CO 2 CH 3 , or —CH 2 CO 2 CH 3 ;

R 16 is —O—C 1 -C 8 alkyl, —O—C 2 -C 8 (hetero)cycloalkyl, —O—C 4 -C 12 (hetero)aryl, —NH 2 , —NH—C 1 -C 8 alkyl, —N(C 1 -C 8 alkyl) 2 ,

R 18 and R 19 are each independently —H or —C 1 -C 8 alkyl;

R 22 and R 23 are each independently absent, —H or —C 1 -C 8 alkyl;

R 24 and R 25 are each independently —H, —CN, —C 1 -C 8 alkyl, —C 2 -C 8 (hetero)cycloalkyl, —CH 2 —O—C 1 -C 8 alkyl, —C(O)—C 1 -C 8 alkyl, —C 1 -C 8 alkylene-C(O)—C 1 -C 8 alkyl, —C(O)—C 2 -C 8 (hetero)cycloalkyl, —C 1 -C 8 alkylene-C(O)—C 2 -C 8 (hetero)cycloalkyl, —CO 2 H, —CO 2 —C 1 -C 8 alkyl, —C 1 -C 8 alkylene-CO 2 —C 1 -C 8 alkyl, —CO 2 —C 2 -C 8 (hetero)cycloalkyl, —C 1 -C 8 alkylene-CO 2 —C 2 -C 8 (hetero)cycloalkyl, —C 1 -C 8 alkylene-NH 2 , —C 1 -C 8 alkylene-NH—C 1 -C 8 alkyl, —C 1 -C 8 alkylene-N(C 1 -C 8 alkyl) 2 , —C(O)NH 2 , —C 1 -C 8 alkylene-C(O)NH 2 , —C(O)NH—C 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C 1 -C 8 alkylene-C(O)NH—C 1 -C 8 alkyl, —C 1 -C 8 alkylene-C(O)N(C 1 -C 8 alkyl) 2 , -(hetero)aryl, -(hetero)cycloalkyl,

R 4 , R 5 , R 12 , R 13 , R 20 , R 21 , R 31 , R 32 , R 33 , and R 34 are each independently —H, —CN, —C 1 -C 8 alkyl, —C 2 -C 8 (hetero)cycloalkyl, —O—C 1 -C 8 alkyl, —CH 2 —O—C 1 -C 8 alkyl, —C(O)—C 1 -C 8 alkyl, —C 1 -C 8 alkylene-C(O)—C 1 -C 8 alkyl, —C(O)—C 3 -C 8 cycloalkyl, —C 1 -C 8 alkylene-C(O)—C 2 -C 8 (hetero)cycloalkyl, —CO 2 H, —CO 2 —C 1 -C 8 alkyl, —C 1 -C 8 alkylene-CO 2 —C 1 -C 8 alkyl, —CO 2 —C 2 -C 8 (hetero)cycloalkyl, —C 1 -C 8 alkylene-CO 2 —C 2 -C 8 (hetero)cycloalkyl, —NH 2 , —C 1 -C 8 alkylene-NH 2 , —NH—C 1 -C 8 alkyl, —N(C 1 -C 8 alkyl) 2 , —C 1 -C 8 alkylene-NH—C 1 -C 8 alkyl, —C 1 -C 8 alkylene-N(C 1 -C 8 alkyl) 2 , —C(O)NH 2 , —C 1 -C 8 alkylene-C(O)NH 2 , —C(O)NH—C 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C 1 -C 8 alkylene-C(O)NH—C 1 -C 8 alkyl, —C 1 -C 8 alkylene-C(O)N(C 1 -C 8 alkyl) 2 , -(hetero)aryl, -(hetero)cycloalkyl,

R 27 and R 28 are each independently —H or —Z—NR 35 R 36 ,

wherein:

Z is a C 1 -C 8 alkylene; and

R 35 and R 36 are each independently —H, —C 1 -C 8 alkyl, -(hetero)aryl, -(hetero)cycloalkyl, —C 1 -C 8 alkylene-OH, —C 1 -C 8 alkylene-NH 2 , —C 1 -C 8 alkylene-NH—C 1 -C 8 alkyl, or —C 1 -C 8 alkylene-N—(C 1 -C 8 alkyl) 2 ;

R 29 and R 30 are each independently absent, —H, —CH 3 , or —CH 2 CH 3 ; and

m, n, and p are each independently 0 or 1.

2 . The compound of claim 1 , wherein R 6 , R 7 , R 22 , R 23 , R 29 , and R 30 are each absent and m, n, and p are each 0.

3 . The compound of any one of claims 1 - 34 , wherein m, n, and p are each 1.

4 . The compound of claim 3 , wherein R 6 is —H, —CH 3 , or —CH 2 CH 3 .

5 . The compound of claim 3 , wherein R 6 is —CN, —C(O)N(CH 3 ) 2 , —CH 2 C(O)N(CH 3 ) 2 , —CO 2 CH 3 , or —CH 2 CO 2 CH 3 .

6 . The compound of any one of claims 3 - 5 , wherein R 7 is —H, —CH 3 , or —CH 2 CH 3 .

7 . The compound of any one of claims 3 - 5 , wherein R 7 is —CN, —C(O)N(CH 3 ) 2 , —CH 2 C(O)N(CH 3 ) 2 , —CO 2 CH 3 , or —CH 2 CO 2 CH 3 .

8 . The compound of any one of claims 3 - 7 , wherein R 22 , R 23 , R 29 , and R 30 is —H, —CH 3 , or —CH 2 CH 3 .

9 . The compound of any one of claims 1 - 8 , wherein R 4 , R 5 , R 12 , R 13 , R 20 , R 21 , R 31 , R 32 , R 33 , and R 34 are each independently —H, —CN, —CH 3 , —CH 2 CH 3 , —OCH 3 , —OCH 2 CH 3 , —C(O)CH 3 , —C(O)CH 2 CH 3 , —CH 2 C(O)CH 3 , —CH 2 COCH 2 CH 3 , —C(O) 2 H, —CO 2 CH 3 , —CO 2 CH 2 CH 3 , —CH 2 CO 2 CH 3 , —CH 2 CO 2 CH 2 CH 3 , —NH 2 , —CH(CH 3 )NH 2 , —CH 2 CH(CH 3 )NH 2 , —CH(CH 3 )CH 2 NH 2 , —C(CH 3 ) 2 NH 2 , —CH 2 C(CH 3 ) 2 NH 2 , —C(CH 3 ) 2 CH 2 NH 2 , —CH 2 NH 2 , —CH 2 CH 2 NH 2 , —CH 2 CH 2 CH 2 NH 2 , —N(CH 3 ) 2 , —N(CH 2 CH 3 ) 2 , —CH 2 N(CH 3 ) 2 , —CH 2 N(CH 2 CH 3 ) 2 , —C(O)N(CH 3 ) 2 , —C(O)N(CH 2 CH 3 ) 2 , —CH 2 C(O)NH 2 , —CH 2 C(O)N(CH 3 ) 2 , —CH 2 C(O)N(CH 2 CH 3 ) 2 , C 4 -C 12 (hetero)aryl, C 2 -C 8 (hetero)cycloalkyl,

10 . The compound of any one of claims 1 - 9 , wherein R 4 , R 5 , R 33 , and R 34 are each independently —H, —CN, —CH 3 , —CH 2 CH 3 , —C(O)CH 3 , —C(O)CH 2 CH 3 , —CH 2 C(O)CH 3 , —CH 2 COCH 2 CH 3 , —CO 2 H, —CO 2 CH 3 , —CO 2 CH 2 CH 3 , —CH 2 CO 2 CH 3 , —CH 2 CO 2 CH 2 CH 3 , —C(O)N(CH 3 ) 2 , —C(O)N(CH 2 CH 3 ) 2 , —CH 2 C(O)NH 2 , —CH 2 C(O)N(CH 3 ) 2 , —CH 2 C(O)N(CH 2 CH 3 ) 2 ,

11 . The compound of any one of claims 1 - 10 , wherein R 4 , R 5 , R 33 , and R 34 are each independently —H, —CN, —CH 3 , —CH 2 CH 3 , —C(O)CH 3 , —CH 2 C(O)CH 3 , —CO 2 H, —CO 2 CH 3 , —CH 2 CO 2 CH 3 , or —C(O)N(CH 3 ) 2 .

12 . The compound of any one of claims 1 - 11 , wherein X is CR 33 R 34 and at least one of R 4 , R 5 , R 33 , and R 34 is not H.

13 . The compound of claim 12 , wherein R 4 is —H and least one of R 5 , R 33 , and R 34 is not —H or R 4 , R 5 , R 33 , and R 34 are each —H and at least one of R 6 and R 7 is not —H.

14 . The compound of any one of claims 1 - 11 , wherein X is O.

15 . The compound of any one of claims 1 - 9 , wherein R 12 is —H; R 13 is —H, —CH 3 , —CH 2 CH 3 , —CN, —C(O)N(CH 3 ) 2 , —CH 2 C(O)N(CH 3 ) 2 , —C(O)N(CH 2 CH 3 ) 2 , —CH 2 C(O)N(CH 2 CH 3 ) 2 , —CO 2 CH 3 , or —CH 2 CO 2 CH 3 ; and R 16 is —OCH 3 , —N(CH 3 ) 2 , or

16 . The compound of any one of claims 1 - 9 , wherein

R 18 and R 19 are each independently —H or —C 1 -C 6 alkyl;

R 20 and R 21 are each independently —H, —CN, —CH 3 , —CH 2 CH 3 , —C(O)CH 3 , —C(O)CH 2 CH 3 , —CH 2 C(O)CH 3 , —CH 2 COCH 2 CH 3 , —C(O) 2 H, —CO 2 CH 3 , —CO 2 CH 2 CH 3 , —CH 2 CO 2 CH 3 , —CH 2 CO 2 CH 2 CH 3 , —C(O)N(CH 3 ) 2 , —C(O)N(CH 2 CH 3 ) 2 , —CH 2 C(O)NH 2 , —CH 2 C(O)N(CH 3 ) 2 , —CH 2 C(O)N(CH 2 CH 3 ) 2 , —C 4 -C 12 (hetero)aryl, —C 2 -C 8 (hetero)cycloalkyl,

R 24 and R 25 are each independently —H, —CN, —C 1 -C 4 alkyl, —C 2 -C 6 (hetero)cycloalkyl, —CH 2 —O—C 1 -C 4 alkyl, —C(O)—C 1 -C 4 alkyl, —C 1 -C 4 alkylene-C(O)—C 1 -C 4 alkyl, —C(O)—C 2 -C 6 (hetero)cycloalkyl, —C 1 -C 4 alkylene-C(O)—C 2 -C 6 (hetero)cycloalkyl, —CO 2 H, —CO 2 —C 1 -C 4 alkyl, —C 1 -C 4 alkylene-CO 2 —C 1 -C 4 alkyl, —CO 2 —C 2 -C 6 (hetero)cycloalkyl, —C 1 -C 4 alkylene-CO 2 —C 2 -C 6 (hetero)cycloalkyl, —C 1 -C 4 alkylene-NH 2 , —C 1 -C 4 alkylene-NH—C 1 -C 4 alkyl, —C 1 -C 4 alkylene-N(C 1 -C 4 alkyl) 2 , —C(O)NH 2 , —C 1 -C 4 alkylene-C(O)NH 2 , —C(O)NH—C 1 -C 4 alkyl, —C(O)N(C 1 -C 4 alkyl) 2 , —C 1 -C 4 alkylene-C(O)NH—C 1 -C 4 alkyl, —C 1 -C 4 alkylene-C(O)N(C 1 -C 4 alkyl) 2 , —C 4 -C 12 (hetero)aryl, or —C 3 -C 6 (hetero)cycloalkyl.

17 . The compound of any one of claims 1 - 9 or 16 , wherein R 21 is —H, —CH 3 , —CH 2 CH 3 , —CO 2 CH 3 , or phenyl; n is 0; and R 22 and R 23 are absent.

18 . The compound of any one of claims 1 - 9 , 16 , or 17 , wherein R 24 is —H, —CN, —C(O)CH 3 , —CO 2 CH 3 , —CH 2 CO 2 CH 3 , —C(O)N(CH 3 ) 2 , phenyl, cyclopentyl, or cyclohexyl and R 25 is —CN, —C(O)CH 3 , —CO 2 CH 3 , —CH 2 CO 2 CH 3 , —C(O)N(CH 3 ) 2 , phenyl, cyclopentyl, or cyclohexyl.

19 . The compound of any one of claims 1 - 9 , wherein R 28 is —Z—NR 35 R 36 , wherein R 35 and R 36 are each independently —H or —C 1 -C 2 alkyl.

20 . The compound of any one of claims 1 - 19 , wherein the compound has a boiling point above about 225° C.

21 . The compound of any one of claims 1 - 20 , wherein the compound has a longer gas chromatography retention time than diethyl adipate, hexadecane, methyl palmitate, or a combination of two or more thereof.

22 . The compound of any one of claims 1 - 21 , wherein the compound is low VOC.

23 . The compound of any one of claims 1 - 22 , wherein the compound has a toxicity lower than N-methyl-2-pyrrolidione.

24 . A composition comprising the compound of Formula I, Formula II, Formula III, Formula IV, or a combination thereof in any one of claims 1 - 23 .

25 . The composition of claim 24 , wherein the composition is substantially free of N-methyl-2-pyrrolidione (NMP).

26 . The composition of claim 24 or claim 25 , wherein the composition is a known composition to contain NMP and the compound replaces the NMP in the composition.

27 . The composition of any one of claims 24 - 26 , wherein the composition is a paint or coating, stripper (e.g., paint, photoresist, furniture, graffiti, wheel, nail polish remover), cleaner (e.g., oven, surface, floor, automotive, industrial, optic, printed circuit board, or semiconductor), adhesive/binder/sealant, leather treatment, personal care (i.e., commonly used as a surfactant), screen printing (e.g., lithographic, silk), pharmaceutical formulation, and/or manufacturing (e.g., electronic such as printed circuit board, defluxing, or semiconductor; pharmaceutical; agrochemical; petrochemicals; plasticizer; ink).

28 . A method of making the compound of Formula I in any one of claims 1 - 23 comprising:

reacting a nitroalkane and an acrylate reagent to form a nitro alkanoyl reagent;

optionally derivatizing the nitro alkanoyl reagent;

reducing the nitro acrylate reagent to form an amino alkanoyl reagent;

optionally derivatizing the amino alkanoyl reagent;

cyclizing the amino alkanoyl reagent to form a compound of Formula Ia:

and

alkylating the compound of Formula Ia;

wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 33 , R 34 , and m are as defined in any one of claims 1 - 23 .

29 . A method of making the compound of Formula I in any one of claims 1 - 23 comprising:

reacting a nitroalkane and a ketone or aldehyde to form a nitroalcohol;

optionally derivatizing the nitroalcohol;

reducing the nitroalcohol to form an aminoalcohol;

optionally derivatizing the aminoalcohol; and

cyclizing the aminoalcohol in the presence of carbon dioxide to form a compound of Formula Id:

and

alkylating the compound of Formula Id;

wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and m are as defined in any one of claims 1 - 23 .

30 . A method of making the compound of Formula II in any one of claims 1 - 23 comprising:

reacting a nitroalkane and an acrylate reagent to form a nitro alkanoyl reagent;

optionally derivatizing the nitro alkanoyl reagent;

reducing the nitro alkanoyl reagent to form a compound of Formula IIa:

and

alkylating the compound of Formula IIa;

wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 14 , and R 16 are as defined in any one of claims 1 - 23 .

31 . A method of making the compound of Formula III in any one of claims 1 - 23 comprising:

reducing a nitroalkane to form an alkylhydroxylamine;

reacting the alkylhydroxylamine and an aldehyde to form a nitrone; and

reacting the nitrone and an alkene.

32 . A method of making the compound of Formula IV in any one of claims 1 - 23 comprising:

reacting a nitroalkane and a maleimide to form a nitropyrrolidine-dione; and

reducing the nitropyrrolidine-dione to form the compound of Formula IV.