Macrocyclic ketones as fragrance materials and methods for making same

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2, R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, R3 are each independently a hydrogen atom or a C1 to C4 alkyl and R5 is the alkyl group of said trialkylorthoacetate;
• hydrogenating said linear bis ester to form a saturated or mono-unsaturated linear bis-ester;
• performing an acyloin condensation of said saturated or mono-unsaturated linear bis-ester to form an α-hydroxyketone;
• and
• reducing said α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, R3 are each independently a hydrogen atom or a C1 to C4 alkyl and R5 is the alkyl group of said trialkylorthoacetate;
• hydrogenating said linear bis-ester to form a saturated or mono-unsaturated linear bis-ester;
• reacting said saturated or mono-unsaturated linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;
• and
• hydrolyzing and decarboxylating said β-ketoester to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• hydrogenating said linear bis-ester to form a saturated or mono-unsaturated linear bis-ester;
• performing an acyloin condensation of said saturated or mono-unsaturated linear bis-ester to form an α-hydroxyketone;
• and
• reducing said α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):

• wherein R1, R2 R3, and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• hydrogenating said linear bis-ester to form a saturated or mono-unsaturated linear bis-ester;
• reacting said saturated or mono-unsaturated linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;
• and
• hydrolyzing and decarboxylating said β-ketoester to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2, and b is an integer in a range from 1 to 6, comprising:
• reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone;
• hydrogenating said α-hydroxyketone to form a saturated or mono-unsaturated α-hydroxyketone;
• and
• reducing said saturated or mono-unsaturated α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;
• hydrogenating said β-ketoester to form a saturated or mono-unsaturated β-ketoester;
• and
• hydrolyzing and decarboxylating said saturated or mono-unsaturated β-ketoester to form a saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone;
• hydrogenating said α-hydroxyketone to form a saturated or mono-unsaturated α-hydroxyketone;
• and
• reducing said saturated or mono-unsaturated α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;
• hydrogenating said β-ketoester to form a saturated or mono-unsaturated β-ketoester;
• and
• hydrolyzing and decarboxylating said saturated or mono-unsaturated β-ketoester to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone;
• reducing said α-hydroxyketone to form a macrocyclic diene ketone;
• and
• hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;
• hydrolyzing and decarboxylating said β-ketoester to form a macrocyclic diene ketone;
• and
• hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester having the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• performing an acyloin condensation of said linear bis-ester to form a α-hydroxyketone;
• reducing said α-hydroxyketone to form a macrocyclic diene ketone;
• and
• hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.

A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):

• wherein R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising:
• reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):
• wherein b is an integer in a range from 1 to 6 and R1, R2 and R3 are each independently a hydrogen atom or a C1 to C4 alkyl;
• reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):
• wherein b is an integer in a range from 1 to 6, R1, R2, and R3 are each independently a hydrogen atom or a C1 to C4 alkyl, and R5 is the alkyl group of said trialkylorthoacetate;
• reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;
• hydrolyzing and decarboxylating said β-ketoester to form a macrocyclic diene ketone;
• and
• hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.