Method for preparation of fluoro, chloro and fluorochloro alkylated compounds by homogeneous catalysis

Patent metadata

Field	Value
Publication number	US-9809596-B1
Application number	US-201515522336-A
Country	US
Kind code	B1
Filing date	Nov 5, 2015
Priority date	Nov 7, 2014
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

The invention discloses a method for preparations of fluoro, chloro and fluorochloro alkylated compounds by homogeneous Pd catalyzed fluoro, chloro and fluorochloro alkylation with fluoro, chloro and fluorochloroalkyl halides in the presence of di(1-adamantyl)-adamantyl-n-butylphosphine and in the presence of 2,2,6,6-tetramethylpiperdine 1-oxyl.

First claim

The invention claimed is:

1. A method for the preparation of a fluoro, chloro or fluorochloro alkylated compound by a reaction of a compound COMPSUBST with a compound FCLALKYLHALIDE by homogeneous catalysis using a catalyst CAT
in the presence of BuPAd 2 and
in the presence of TEMPO and
in the presence of a compound BAS,
BAS is selected from the group consisting of Cs 2 CO 3 , CsHCO 3 , NEt 3 , and mixtures thereof;
FCLALKYLHALIDE is a compound of formula (III);
R3—X   (III)

X is Cl, Br or I;
R3 is C 1-20 alkyl or a C 1-20 alkyl, wherein in the alkyl chain at least one of the hydrogens is substituted by F or Cl;
CAT is selected from the group consisting of Pd(OAc) 2 , Pd(TFA) 2 , and mixtures thereof;
COMPSUBST is selected from the group consisting of a compound COMPSUBST-I, ethene, cyclohexene, ethine, and polystyrene;
the ethene and the cyclohexene being unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl, naphthyl and morpholine;
the ethine being unsubstituted or substituted by 1 substituent selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl and naphthyl;

COMPSUBST-1 contains a ring RINGA;
RINGA is an unsaturated or aromatic, 5 or 6 membered carbocyclic or heterocyclic ring,
when RINGA is a heterocyclic ring, then RINGA has 1, 2 or 3 identical or different endocyclic heteroatoms independently from each other selected from the group consisting of N, O and S,
when RINGA is a 5 membered ring, then RINGA is unsubstituted or substituted by 1, 2, 3 or 4 identical or different substituents,
when RINGA is a 6 membered ring then RINGA is unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or different substituents,
any of said substituents of RINGA is independently from any other of said substituent of RINGA selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, OH, N(R10)R11, CN, NH—OH, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C═C—R24, benzyl, phenyl and naphthyl;
RINGA can be condensed with a ring RINGB, RINGB is a 5 or 6 membered carbocyclic or heterocyclic ring,
when RINGB is a heterocyclic ring, is contains 1, 2 or 3 identical or different endocyclic heteroatoms independently from each other selected from the group consisting of N, O and S;
RINGB is unsubstituted or substituted with 1, 2 or 3 in case of RINGB being a 5 membered ring, with 1, 2, 3 or 4 in case of RINGB being a 6 membered ring, identical or different substituents independently from each other selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, OH, N(R17)R18, CN, NH—OH, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) n —C(O)Y2, S(O) 2 R51, CH═C(H)R38, C≡C-R34 benzyl, phenyl and naphthyl;
any of said C 1-10 alkyl substituent of RINGA or RINGB is unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, OH, O—C(O)—C 1-5 alkyl, O—C 1-10 alkyl, S—C 1-10 alkyl, S(O)—C 1-10 alkyl, S(O 2 )-C 1-10 alkyl, O—C 1-6 alkylen-O—C 1-6 alkyl, C 3-8 cycloalkyl and 1,2,4-triazolyl;
any of said benzyl, phenyl and naphthyl substituent of RINGA or RINGB is independently from each other unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, C 1-4 alkoxy, NO 2 and CN;

m, n and q are identical or different and independently from each other 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
Y1, Y2 and R13 are identical or different and independently from each other selected from the group consisting of H, OH, C(R14)(R15)R16, C 1-6 alkyl, O—C 1-6 alkyl, phenyl, benzyl, O-phenyl, O—C 1-6 alkylen-O—C 1-6 alkyl and N(R19)R20;
R14, R15 and R16 are identical or different and independently from each other selected from the group consisting of H, F, Cl and Br;
R10, R11, R17, R18, R19 and R20 are identical or different and are independently from each other H or C 1-6 alkyl, or R10 and R11, R17 and R18 or R19 and R20 represent together a tetramethylene or a pentamethylene chain;
R50 and R51 are identical or different and independently from each other selected from the group consisting of OH, C 1-6 alkyl and C 1-6 alkoxy;
R24, R34, R28 and R38 are identical or different and independently from each other selected from the group consisting of H, C 1-10 alkyl, C(R25)(R26)—O—R27;
R25, R26 and R27 are identical or different and independently from each other selected from the group consisting of H and C 1-10 alkyl.

2. The method according to claim 1 , wherein
COMPSUBST is selected from the group consisting of compound COMPSUBST-I, ethene, cyclohexene, ethine, and polystyrene;
the ethene and the cyclohexene being unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of C 1-10 alkyl, C 3-6 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, benzyl, phenyl, naphthyl and morpholine;
the ethine being unsubstituted or substituted by 1 substituent selected from the group consisting of C 1-10 alkyl, C 3-6 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, benzyl, phenyl and naphthyl;

with COMPSUBST-I being selected from the group consisting of

with COMPSUBST-I being unsubstituted or substituted
by 1, 2, 3 or 4 in case of COMPSUBST-I being a monocyclic compound with 5 endocyclic atoms,
by 1, 2, 3, 4 or 5 in case of COMPSUBST-I being a monocyclic compound with 6 endocyclic atoms,
by 1, 2, 3, 4, 5 or 6 in case of COMPSUBST-I being a bicyclic compound wherein a 5-membered and a 6-membered ring are ortho-fused,
by 1, 2, 3, 4, 5, 6 or 7 in case of COMPSUBST-I being a bicyclic compound wherein two 6-membered rings are ortho-fused,
identical or different substituents independently from each other selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, OH, C(H)═O, N(R10)R11, CN, NH—OH, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl and naphthyl;

said C 1-10 alkyl substituent of COMPSUBST-I is unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, OH, O—C(O)—C 1-5 alkyl, O—C 1-10 alkyl, S—C 1-10 alkyl, S(O)—C 1-10 alkyl, S(O 2 )—C 1-10 alkyl, O—C 1-6 alkylen-O—C 1-6 alkyl, C 3-8 cycloalkyl and 1,2,4-triazolyl;
said benzyl, phenyl and naphthyl substituent of COMPSUBST-I is independently from each other unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, C 1-4 alkoxy, NO 2 and CN.

3. The method according to claim 1 , wherein m, n and q are identical or different and independently from each other 0, 1, 2, 3 or 4.

4. The method according to claim 1 , wherein
COMPSUBST is selected from the group consisting of benzene, pyrazole,

compound of formula (VI), ethene, cyclohexene, ethine, and polystyrene;
Y is C 1-6 alkyl;
the ethene and the cyclohexene being unsubstituted or substituted by 1

Assignees

• Lonza Ag
• Lonza Ag

Inventors

• Taeschler Christoph
• Zaragoza Doerwald Florencio
• Ellinger Stefan
• Beller Matthias
• Neumann Helfried
• He Lin
• Natte Kishore

Classifications

• C07C41/30 Primary

  by increasing the number of carbon atoms, e.g. by oligomerisation · CPC title

• C07C17/272

  by addition reactions · CPC title

• C07D473/10 Primary

  with methyl radicals in positions 3 and 7, e.g. theobromine · CPC title

• C07D209/10

  with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring · CPC title

• C07D333/12

  Radicals substituted by halogen atoms or nitro or nitroso radicals · CPC title