Decomposition of organic peroxides and hydrogen peroxide by the iron thiolates and related complexes
Disclosed herein is a method of reducing or disproportionating peroxide, comprising combining an organic chalcogenide, an iron salt, and the peroxide in the presence of an additional reductant, which can be the organic chalcogenide. The method can be used to, e.g., prepare alcohols from peroxides and to disproportionate hydrogen peroxide into water and oxygen.
1. A method of decomposing a peroxide of Formula I:
R 1 —O—O—R 2 (Formula I)
wherein:
each of R 1 and R 2 is independently selected from the group consisting of:
(i) hydrogen;
(ii) C 1-10 alkyl optionally substituted with 1-4 R a ;
(iii) C 3-10 alkenyl optionally substituted with 1-4 R a ;
(iv) C 3-10 alkynyl optionally substituted with 1-4 R a ;
(v) C 6-10 aryl optionally substituted with 1-4 R a ;
(vi) 5-10 membered heteroaryl including 5-10 ring atoms, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S, wherein the heteroaryl is optionally substituted with 1-4 R a ;
(vii) C 3-10 cycloalkyl that is optionally substituted with 1-4 R a ;
(vii) 5-10 membered heterocyclyl including 3-10 ring atoms, wherein 1-3 ring atoms are each independently selected from the group consisting of N, NH and O, wherein the heterocyclyl is optionally substituted with 1-4 R a ;
(viii) —C(O)R b ;
(ix) —CO 2 R b ;
(x) —Si(R′) 3 ;
each occurrence of R a is independently selected from the group consisting of:
(i) C 1-8 alkyl substituted with 1-3 R b ;
(ii) (C 0-6 alkylene)-C 3-10 cycloalkyl, wherein the cycloalkyl is optionally substituted with from 1-4 R b ;
(iii) (C 0-6 alkylene)-heterocyclyl including 3-10 ring atoms, wherein 1-3 ring atoms are each independently selected from the group consisting of NH, O, and S, wherein the heterocyclyl is optionally substituted with 1-4 R b ;
(iv) (C 0-6 alkylene)-(C 6-10 aryl), wherein the aryl is optionally substituted with 1-5 R b ; or
(v) (C 0-6 alkylene)-heteroaryl including 5-10 ring atoms, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S, wherein the heteroaryl is optionally substituted with 1-3 R b ;
(vi) C 1-4 alkoxy optionally substituted with 1-3 R b ;
(vii) C 1-4 haloalkoxy;
(viii) —COH;
(ix) —CO 2 R b ;
(x) —CONR b R b ;
(xi) cyano;
(xii) —NR b R b ;
(xiii) —NR b C(O)NR b R b ;
(xiv) —NR b C(O)OR b ;
(xv) —NR b C(O)R b ;
(xvi) C 1-4 thioalkoxy;
(xvii) —N 3 ;
(xviii) —CO 2 H;
(xix) —C(O)R b ;
(xx) —SO 1-2 (R b );
(xxi) —O n P(O) n Y 2 , wherein n is independently 0 or 1, and wherein each Y is independently selected from —OR b and C 1-6 alkyl;
(xxii) —O—O—R c ;
(xxiii) —(O—O—CH 2 CH 2 ) m —O—OR′″, wherein m is an integer from 1-1000; and
alternatively, any two R a , taken together with the atoms they are bonded to and any atoms that intervene the atoms they are bonded to, form a ring selected from:
(i) a C 3-10 cycloalkyl, wherein the a C 3-10 cycloalkyl is optionally substituted with 1-6 R b ;
(ii) a 5-10-membered heterocyclyl comprising 1-6 heteroatoms selected O, S, and N, wherein the heterocyclyl is optionally substituted with 1-6 R b ;
(iii) a C 6-10 aryl, wherein the aryl is optionally substituted with 1-6 R b ; and
(iv) a 5-10 membered heteroaryl comprising 1-6 heteroatoms selected O, S, and N, wherein the heteroaryl is optionally substituted with 1-6 R b ; and
5-10-membered heterocyclyl comprising 1-6 heteroatoms selected O, S, and N, wherein the heterocyclyl is optionally substituted with 1-6 R b ;
each occurrence of R b is independently selected from the group consisting of:
(i) halo;
(ii) cyano;
(iii) C 1-6 alkyl;
(iv) C 2-6 alkenyl;
(v) C 2-6 alkynyl;
(vi) C 1-4 haloalkyl;
(vii) C 1-4 alkoxy;
(viii) C 1-4 haloalkoxy;
(ix) —(C 0-3 alkylene)-C 3-6 cycloalkyl optionally substituted with 1-4 independently selected C 1-4 alkyl;
(x) —(C 0-3 alkylene)-heterocyclyl including 3-10 ring atoms, wherein 1-3 ring atoms are each independently selected from the group consisting of NH, O, and S, wherein the heterocyclyl is optionally substituted with 1-4 independently selected C 1-4 alkyl;
(xi) —(C 0-3 alkylene)-phenyl;
(xii) —(C 0-3 alkylene)-heteroaryl including 5-10 ring atoms, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S;
(xiii) —S(O) 1-2 (C 1-4 alkyl); and
(xiv) —NR′R″;
(xv) —OH;
(xvi) —S(O) 1-2 (NR′R″);
(xvii) —C 1-4 thioalkoxy;
(xviii) —NO 2 ;
(xix) —N(R′)(C(═O)C 1-3 alkyl);
(xx) —C(═O)(C 1-4 alkyl);
(xxi) —C(═O)O(C 1-4 alkyl);
(xxii) —C(═O)OH, and
(xxiii) —C(═O)N(R′)(R″); and
alternatively, any two R b , taken together with the atoms they are bonded to and any atoms that intervene the atoms they are bonded to, form a ring selected from:
(i) a C 3-10 cycloalkyl, wherein the a C 3-10 cycloalkyl is optionally substituted with 1-6 R d ;
(ii) a 5-10-membered heterocyclyl comprising 1-6 heteroatoms selected O, S, and N, wherein the heterocyclyl is optionally substituted with 1-6 R d ;
(iii) a C 6-10 aryl, wherein the aryl is optionally substituted with 1-6 R d ; and
(iv) a 5-10 membered heteroaryl comprising 1-6 heteroatoms selected O, S, and N, wherein the heteroaryl is optionally substituted with 1-6 R d ; and
5-10-membered heterocyclyl comprising 1-6 heteroatoms selected O, S, and N, wherein the heterocyclyl is optionally substituted with 1-6 R d ;
each occurrence of R c is independently selected from the group consisting of:
(i) hydrogen;
(ii) C 1-10 alkyl optionally substituted with 1-4 R d ;
(iii) C 3-10 alkenyl optionally substituted with 1-4 R d ;
(iv) C 3-10 alkynyl optionally substituted with 1-4 R d ;
(v) C 6-10 aryl optionally substituted with 1-4 R d ;
(vi) 5-10 membered heteroaryl including 5-10 ring atoms, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S, wherein the heteroaryl is optionally substituted with 1-4 R d ;
(vii) C 3-10 cycloalkyl that is optionally substituted with 1-4 R d ;
(vii) 5-10 membered heterocyclyl including 3-10 ring atoms, wherein 1-3 ring atoms are each independently selected from the group consisting of N, NH and O, wherein the heterocyclyl is optionally substituted with 1-4 R d ;
(viii) —C(O)R b ;
(ix) —CO 2 R b ; and
(x) —Si(R′) 3 ;
each occurrence of R d is independently selected from the group consisting of:
(i) C 1-8 alkyl substituted with 1-3 R b ;
(ii) (C 0-6 alkylene)-C 3-10 cycloalkyl, wherein the cycloalkyl is optionally substituted with from 1-4 R b ;
(iii) (C 0-6 alkylene)-heterocyclyl including 3-10 ring atoms, wherein 1-3 ring atoms are each independently selected from the group consisting of NH, O, and S, wherein the heterocyclyl is optionally substituted with 1-4 R b ;
(iv) (C 0-6 alkylene)-(C 6-10 aryl), wherein the aryl is optionally substituted with 1-5 R b ; or
(v) (C 0-6 alkylene)-heteroaryl including 5-10 ring atoms, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S, wherein the heteroaryl is optionally substituted with 1-3 R b ;
(vi) C 1-4 alkoxy optionally substituted with 1-3 R b ;
(vii) C 1-4 haloalkoxy;
(viii) —COH;
(ix) —CO 2 R b ;
(x) —CONR b R b ;
(xi) cyano;
(xii) —NR b R b ;
(xiii) —NR b C(O)NR b R b ;
(xiv) —NR b C(O)OR b ;
(xv) —NR b C(O)R b ;
(xvi) C 1-4 thioalkoxy;
(xvii) —N 3 ;
(xviii) —CO 2 H;
(xix) —C(O)R b ;
(xx) —SO 1-2 (R b ); and
(xxi) —O n P(O) n Y 2 , wherein n is independently 0 or 1, and wherein each Y is independently selected from —OR b and C 1-6 alkyl; and
each occurrence of R′, R″, and R′″ is independently selected from the group consisting of: H, C 1-4 alkyl, and phenyl; or, if R′ and R″ are bonded to the same atom, R′ and R″ together with the atom to which each is attached forms a ring including 3-8 ring atoms, wherein the ring includes: (a) 1-7 ring carbon atoms; and (b) 0-3 ring heteroatoms (in addition to the atom attached to R′ and R″), which are each independently selected from the group consisting of N, NH, O, and S;
alternatively, R 1 and R 2 , taken together with the oxygen atoms they are bonded to, form a 5-10-membered heterocyclyl comprising 1-6 heteroatoms selected from O, S, and N,
wherein the heterocyclyl is optionally substituted with 1-6 R a ; and
provided that when one of R 1 and R 2 is hydrogen, the other of R 1 and R 2 is not hydrogen; and
provided that a —O—O— moiety is not bonded to a carbon that is double bonded to another carbon or triple-bonded to another carbon;
comprising combining:
(i) an organic chalcogenide selected from:
(i-a) a thiol of Formula A1 or a thiolate of Formula A2
R 10 —SH (Formula A1) or R 10 —S − (Formula A2)
wherein:
R 10 is selected from the group consisting of:
(i) C 1-6 alkyl optionally substituted with from 1-4 R m ;
(ii) —C 6-10 aryl optionally substituted with from 1-4 R m ;
(iii) -5-10 membered heteroaryl, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S, wherein the heteroaryl is optionally substituted with from 1-4 R m ;
(iv) —C 3-10 cycloalkyl wherein the cycloalkyl is optionally substituted with from 1-4 R m ; and
(v) -5-10 membered heterocyclyl, wherein the heterocyclyl is optionally substituted with 1-4 R m ;
each occurrence of R m is independently selected from the group consisting of:
(i) C 1-8 alkyl substituted with 1-3 R n ;
(ii) (C 0-6 alkylene)-C 3-10 cycloalkyl, wherein the cycloalkyl is optionally substituted with from 1-4 R n ;
(iii) (C 0-6 alkylene)-heterocyclyl including 3-10 ring atoms, wherein 1-3 ring atoms are each independently selected from the group consisting of NH, O, and S, wherein the heterocyclyl is optionally substituted with 1-4 R n ;
(iv) (C 0-6 alkylene)-(C 6-10 aryl), wherein the aryl is optionally substituted with 1-5 R n ; or
(v) (C 0-6 alkylene)-heteroaryl including 5-10 ring atoms, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S, wherein the heteroaryl is optionally substituted with 1-3 R n ;
(vi) C 1-4 alkoxy optionally substituted with 1-3 R n ;
(vii) C 1-4 haloalkoxy;
(viii) —COH;
(ix) —CO 2 R n ;
(x) —CONR n R n ;
(xi) cyano;
(xii) —NR n R n ;
(xiii) —NR n C(O)NR n R n ;
(xiv) —NR n C(O)OR n ;
(xv) —NR n C(O)R n ;
(xvi) C 1-4 thioalkoxy;
(xvii) —N 3 ;
(xviii) —CO 2 H;
(xix) —C(O)R n ;
(xx) —SO 1-2 (R n );
(xxi) —O n P(O) n Y 2 , wherein n is independently 0 or 1, and wherein each Y is independently selected from —OR n and C 1-6 alkyl;
(xxii) —S − ;
(xxix) C 2-6 alkenyl optionally substituted with 1-3 R n ;
(xxx) C 2-6 alkynyl optionally substituted with 1-3 R n ;
each occurrence of R n is independently selected from the group consisting of:
(i) halo;
(ii) cyano;
(iii) C 1-6 alkyl;
(iv) C 2-6 alkenyl;
(v) C 2-6 alkynyl;
(vi) C 1-4 haloalkyl;
(vii) C 1-4 alkoxy;
(viii) C 1-4 haloalkoxy;
(ix) —(C 0-3 alkylene)-C 3-6 cycloalkyl optionally substituted with 1-4 independently selected C 1-4 alkyl;
(x) —(C 0-3 alkylene)-heterocyclyl including 3-10 ring atoms, wherein 1-3 ring atoms are each independently selected from the group consisting of NH, O, and S, wherein the heterocyclyl is optionally substituted with 1-4 independently selected C 1-4 alkyl;
(xi) —(C 0-3 alkylene)-phenyl;
(xii) —(C 0-3 alkylene)-heteroaryl including 5-10 ring atoms, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S;
(xiii) —S(O) 1-2 (C 1-4 alkyl); and
(xiv) —NR*R**;
(xv) —OH;
(xvi) —S(O) 1-2 (NR*R**);
(xvii) —C 1-4 thioalkoxy;
(xviii) —NO 2 ;
(xix) —N(R*)(C(═O)C 1-3 alkyl);
(xx) —C(═O)(C 1-4 alkyl);
(xxi) —C(═O)O(C 1-4 alkyl);
(xxii) —C(═O)OH, and
(xxiii) —C(═O)N(R*)(R**); and
each occurrence of R* and R** is independently selected from the group consisting of: H, C 1-4 alkyl, and phenyl; or
(i-b) a selenol or selenide of Formula B:
R 20 —Se − or R 20 —SeH (Formula B)
wherein:
R 20 is selected from the group consisting of:
(ii) C 1-6 alkyl;
(iii) C 2-6 alkenyl;
(iv) C 2-6 alkynyl;
(v) —C 6-10 aryl;
(vi) -5-10 membered heteroaryl, wherein 1-4 ring atoms are each independently selected from the group consisting of N, NH, O, and S;
(vii) —C 3-10 cycloalkyl; and
(vii) -5-10 membered heterocyclyl;
(ii) an optional reductant;
(iii) an iron salt selected from an iron (II) halide or an iron (III) halide; and
(iv) the peroxide;
wherein decomposing the peroxide comprises reducing the peroxide or disproportionating the peroxide; and wherein R 1 and R 2 , taken together with the oxygen atoms they are bonded to, form a 5-10-membered heterocyclyl comprising 1-6 heteroatoms selected from O, S, and N, wherein the heterocyclyl is optionally substituted with 1-6 R a .
2. The method of claim 1 , wherein R 10 is C 6-10 aryl.
3. The method of claim 1 , wherein R 10 is phenyl.
4. The method of claim 1 , wherein the iron salt is an iron (II) halide.
5. The method of claim 4 , wherein the iron salt is iron (II) bromide.
6. The method of claim 1 , wherein the ratio of the iron salt to the peroxide is about 0.001:1 to about 0.02:1.
7. The method of claim 1 , wherein the optional reductant is present.
8. The method of claim 1 , wherein the product of the reduction of the peroxide is an alcohol.