Use of ruthenium complexes for formation and/or hydrogenation of amides and related carboxylic acid derivatives

Patent metadata

Field	Value
Publication number	US-9290441-B2
Application number	US-201213471037-A
Country	US
Kind code	B2
Filing date	May 14, 2012
Priority date	Oct 30, 2007
Publication date	Mar 22, 2016
Grant date	Mar 22, 2016

Abstract

A process for preparing amides by reacting a primary amine and a primary alcohol in the presence of a Ruthenium complex to generate the amide and molecular hydrogen. Primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only byproduct) in high yields and high turnover numbers. Also disclosed are processes for hydrogenation of amides to alcohols and amines; hydrogenation of organic carbonates to alcohols; hydrogenation of carbamates or urea derivatives to alcohols and amines; amidation of esters; acylation of alcohols using esters; coupling of alcohols with water and a base to form carboxylic acids; dehydrogenation of beta-amino alcohols to form pyrazines and cyclic dipeptides; and dehydrogenation of secondary alcohols to ketones. These reactions are catalyzed by a Ruthenium complex which is based on a dearomatized PNN-type ligand of formula A1 or precursors thereof of formulae A2 or A3.

First claim

What is claimed is:

1. A process for hydrogenating an amide to generate an alcohol and amine, which process comprises reacting the amide with molecular hydrogen (H 2 ), in the absence of a solvent or in a solvent system consisting of an organic solvent, in the presence of a Ruthenium complex represented by the structure of formula A1′, A2′ or A3′:

wherein
L 1 is N(R) 2 ;
L 2 is selected from the group consisting of nucleophilic carbene (:CR 2 ), P(R 2 ), P(OR) 2 , N(R) 2 , imine, SR, SH, S(═O)R, heteroaryl wherein the heteroatom is selected from nitrogen and sulfur, As(R 2 ), Sb(R) 2 and an N-heterocyclic carbene represented by the structure:

wherein each of R, R 1 , R 2 and R 3 are independently selected from the group consisting of alkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl;
L 3 is a mono-dentate two-electron donor selected from the group consisting of CO, P(R) 3 , P(OR) 3 , NO + , As(R) 3 , Sb(R) 3 , S(R) 2 , nitrile (RCN) and isonitrile (RNC) wherein R is as defined above;
L 4 is absent or is L 3 ;
Y and Z are each independently H or an anionic ligand selected from the group consisting of halogen, OCOR, OCOCF 3 , OSO 2 R, OSO 2 CF 3 , CN, OH, OR, N(R 2 ), RS and SH; wherein R is as defined above;
X represents zero, one, two or three substituents selected from the group consisting of alkyl, aryl, halogen, nitro, amide, ester, cyano, alkoxy, cycloalkyl, alkylaryl, heterocyclyl, heteroaryl, an inorganic support and a polymeric moiety; and
anion represents a group bearing a single negative charge
wherein the process comprises the step of hydrogenating an amide represented by the formula R 4 C(═O)—N—R 5 R 5′ to an alcohol of formula R 4 CH 2 OH and amine of formula R 5 R 5′ NH:

wherein R 4 , R 5 and R 5′ are each independently selected from the group consisting of H, an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl.

2. The process of claim 1 , wherein the process is conducted either with (a) Ruthenium complex A1′ in the absence of a base; or (b) Ruthenium complex A2′ or A3′ in the presence of one or two equivalents of base relative to the amount of the Ruthenium complex.

3. The process of claim 1 , wherein the complex is represented by the structure of formula 1:

4. The process of claim 1 , wherein the amide is selected from the group consisting of N-benzyl-2-methoxyacetamide, N-hexyl-2-methoxyacetamide, N-hexyl-3-methyloxetane-3-carboxamide, N-hexyl-2-furanylcarboxamide, N-benzylbenzamide, N-ethylacetamide, N-methylpropionamide, N-cyclohexyl-2-methoxyacetamide, N-phenylacetamide, N-phenylhexylamide, 2-methoxy-N-phenylacetamide, N-phenylbenzamide, Ethylenediamine-N,N′-(2-methoxyacetamide), N-hexanoylmorpholine, N-butanoylmorpholine, N-2-metoxyacetylpyrrolidine, N-formylmorpholine, N,N-dimethylformamide, N,N-diethylbenzamide, benzamide, 4-methylbenzamide, cyclohexanecarboxamide, hexanamide, acetamide, acrylamide and pivalamide.

5. The process of claim 1 , wherein when the amide is a cyclic amide (lactam), the process results in an amino alcohol, or wherein the amide is a polyamide or a polypeptide.

6. A process for hydrogenating an organic carbonate represented by the formula R 8 O—C(═O)—OR 8′ to the corresponding alcohols(s) and methanol:

wherein R 8 and R 8′ are the same or different and are selected from the group consisting of an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl, which process comprises reacting the carbonate with molecular hydrogen (H 2 ), in the presence of a Ruthenium complex represented by the structure of formula A1′, A2′ or A3′:

wherein
L 1 is N(R) 2 ;
L 2 is selected from the group consisting of nucleophilic carbene (:CR 2 ), P(R 2 ) P(OR) 2 , N(R) 2 , imine, SR, SH, S(═O)R, heteroaryl wherein the heteroatom is selected from nitrogen and sulfur, As(R 2 ), Sb(R) 2 and an N-heterocyclic carbene represented by the structure:

wherein each of R, R 1 , R 2 and R 3 are independently selected from the group consisting of alkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl;
L 3 is a mono-dentate two-electron donor selected from the group consisting of CO, P(R) 3 , P(OR) 3 , NO + , As(R) 3 , Sb(R) 3 , S(R) 2 , nitrile (RCN) and isonitrile (RNC) wherein R is as defined above;
L 4 is absent or is L 3 ;
Y and Z are each independently H or an anionic ligand selected from the group consisting of halogen, OCOR, OCOCF 3 OSO 2 R OSO 2 CF 3 , CN, OH, OR, N(R 2 ), RS and SH; wherein R is as defined above;
X represents zero, one, two or three substituents selected from the group consisting of alkyl, aryl, halogen, nitro, amide, ester, cyano, alkoxy, cycloalkyl, alkylaryl, heterocyclyl, heteroaryl, an inorganic support and a polymeric moiety; and
anion represents a group bearing a single negative charge.

7. The process of claim 6 , wherein the carbonate is dimethyl carbonate, diethyl carbonate, dipropyl carbonate or dibutyl carbonate.

8. A process for hydrogenating a carbamate represented by the formula R 9 O—C(═O)—NHR 10 to the corresponding amine, alcohol and methanol:

wherein R 9 is selected from the group consisting of an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl; and
R 10 is selected from the group consisting of H or an unsubstituted or substituted alkyl, alkoxyalkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl, which process comprises reacting the carbamate with molecular hydrogen (H 2 ), in the presence of a Ruthenium complex represented by the structure of formula A1′, A2′ or A3′:

wherein
L 1 is N(R) 2 ;
L 2 is selected from the group consisting of nucleophilic carbene (:CR 2 ), P(R 2 ) P(OR) 2 , N(R) 2 , imine, SR, SH, S(═O)R, heteroaryl wherein the heteroatom is selected from nitrogen and sulfur, As(R 2 ), Sb(R) 2 and an N-heterocyclic carbene represented by the structure:

wherein each of R, R 1 , R 2 and R 3 are independently selected from the group consisting of alkyl, cycloalkyl, aryl, alkylaryl, heterocyclyl and heteroaryl;
L 3 is a mono-dentate two-electron donor selected from the group consisting of CO, P(R) 3 , P(OR) 3 , NO + , As(R) 3 , Sb(R) 3 , S(R) 2 , nitrile (RCN) and isonitrile (RNC) wherein R is as defined above;
L 4 is absent or is L 3 ;
Y and Z are each independently H or an anionic ligand selected from the group consisting of halogen, OCOR, OCOCF 3 OSO 2 R OSO 2 C

Assignees

• Milstein David
• Gunanathan Chidambaram
• Ben-David Yehoshua
• Balaraman Ekambaram
• Gnanaprakasam Boopathy
• Zhang Jing
• Yeda Res & Dev

Inventors

• Milstein David
• Gunanathan Chidambaram
• Ben-David Yehoshua
• Balaraman Ekambaram
• Gnanaprakasam Boopathy
• Zhang Jing

Classifications

• C07C233/05

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07C233/36

  having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton · CPC title

• C07C67/03

  by reacting an ester group with a hydroxy group · CPC title

• C07C213/00

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title

• C08L79/02

  Polyamines · CPC title