Method of preparing benzazepines and derivatives thereof

A method of preparing at least one benzazepine compound of general formula (IA):

• in which:
• R1 is chosen from the group consisting of halogen atoms chosen from the group consisting of chlorine, fluorine, bromine and iodine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituent groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(ORl), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkRl, —(CH2)mSO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(ORl), —(CH2)m—SiRkRlRm, —(CH2)m—COORk, —(CH2)m—NCORk, and —(CH2)m—NRkRl, and:
• Rk, Rl and Rm are each independently chosen from the group consisting of hydrogen atom, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, and heterocycles,
• or Rk and Rl form, together with the atom to which they are attached, a heterocycle,
• with m denoting an integer greater than or equal to 0,
• n represents an integer chosen from the group consisting of 0, 1, 2, 3 and 4, with, when n is greater than or equal to 2, r the corresponding Rl groups are identical or different, and optionally form, together, a hydrocarbon-based ring or a heterocycle,
• R2, R3, R4, R5, R6 and R7, independently of one another, are chosen from the group consisting of hydrogen atom, halogen atoms chosen from the group consisting of chlorine, fluorine and bromine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituents groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(ORl), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkRl, —(CH2)m—SO3Rk, —(CH2)m-NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(ORl), —(CH2)m—SiRkRlRm, —(CH2)m—COORk, —(CH2)m—NCORk, and —(CH2)m—NRkRl, with Rk, Rl, Rm and m as defined above,
• or R4, R5, R6 and R7 form, in pairs, one or more hydrocarbon-based ring(s) or heterocycle(s), with at least one of the R4, R5, R6 and R7 groups representing a hydrogen atom,
• from at least one compound of general formula (IIA)
• in which
• Z1 represents a group chosen from the group consisting of:
• (i) alkyl groups, acyl groups, aryl groups, aralkyl groups, alkene groups, alkyne groups, hydrocarbon-based rings, and heterocycles,
• (ii) —ORa or —SRa groups in which Ra is a group chosen from the group consisting of:
• alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, and polymer chains;
• —CRbRcPO(ORd)(ORe) groups in which:
• Rb and Rc are each, independently of one another, chosen from the group consisting of hydrogen atom, halogen atoms, alkyl groups, perfluoroalkyl groups, hydrocarbon-based rings, heterocycles, —NO2 groups, —NCO groups, —CN groups, and groups chosen from the group consisting of —Rf, —SO3Rf, —ORf, —SRf, —NRfRg, —COORf, —O2CRf, —CONRfRg, —NRfCORg, in which Rf and Rg are each independently chosen from the group consisting of alkyl groups, alkenyl groups, alkynyl groups, cycloalkenyl groups, cycloalkynyl groups, and aryl groups optionally condensed with a heterocycle, alkaryl, arylalkyl or heteroaryl,
• or Rb and Rc form, together with the carbon atom to which they are attached, a C═O group, a C═S group, a hydrocarbon-based ring or a heterocycle;
• and
• Rd and Re are each, independently of one another, chosen from the group consisting of alkyl groups, alkenyl groups, alkynyl groups, cycloalkenyl groups, cycloalkynyl groups, and aryl groups optionally condensed with a heterocycle, alkaryl, arylalkyl or heteroaryl;
• or Rd and Re form, together, a hydrocarbon-based chain containing from 2 to 4 carbon atoms, optionally interrupted with a group chosen from —O—, —S—and —NRh—;
• where Rh is chosen from the group consisting of alkyl groups, alkenyl groups, alkynyl groups, cycloalkenyl groups, cycloalkynyl groups, and aryl groups optionally condensed with a heterocycle, alkaryl, arylalkyl or heteroaryl;
• (iii) an —NRi Rj group, in which:
• Ri and Rj are each, independently of one another, chosen from the group consisting of radicals chosen from alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, ester groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings and heterocycles;
• or
• Ri and Rj form, together, a hydrocarbon-based chain containing from 2 to 4 carbon atoms, optionally interrupted with an —O—, —S—, or —NRh— group, where Rh is as defined above;
• R2a a represents a group chosen from the group consisting of hydrogen atoms, halogen atoms, alkyl groups, haloalkyl groups, acyl groups, aryl groups, arylalkyl groups, hydrocarbon-based rings, heterocycles, polymer chains and groups chosen from the group consisting of —CH2)m—ORk, —CH(ORk)(ORl), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2R k, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(ORl), (CH2)m—SiRkRlRm, —(CH2)m—COORk, —(CH2)m—NCORkand —(CH2)m—NRkRl, in which Rk, Rl, Rm and m are as defined above,
• R1 and n are as defined above,
• wherein the method comprises at least stages a-e:
• a—reacting said compound of general formula (IIA) with at least one olefin of general formula (A)
• in which:
• R4, R5, R6 and R7 are as defined above, with at least one of the R4, R5, R6 or R7 groups representing a hydrogen atom,
• so as to obtain at least one compound of general formula (IIIA)
• in which:
• R1, R2a, R4, R5, R6, R7, Zl and n are as defined above,
• b—cyclizing, by radical-based process, said compound of general formula (IIIA) so as to obtain at least one tetralone compound of general formula (IVA)
• in which:
• R1, R2a, R4, R5, R6, R7and n are as defined above,
• c—converting said compound of general formula (IVA) into at least its oxime derivative of general formula (VA)
• in which:
• R1, R2a, R4, R5, R6, R7and n are as defined above,
• d—converting said compound of general formula (VA), by Beckmann rearrangement and consecutive reduction(s), into at least one compound of general formula (IA), and
• e—recovering said compound of general formula (IA).

A method of preparing at least one compound of general formula (IB)

• in which:
• R1 is chosen from the group consisting of halogen atoms chosen from the group consisting of chlorine, fluorine, bromine and iodine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituent groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), —(CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk, and —(CH2)m—NRkR1, and:
• Rk, R1 and Rm are each independently chosen from the group consisting of hydrogen atom, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, and heterocycles,
• or Rk and R1 form, together with the atom to which they are attached, a heterocycle,
• with m denoting an integer greater than or equal to 0,
• n represents an integer chosen from the group consisting of 0, 1, 2, 3 and 4, with, when n is greater than or equal to 2, r the corresponding R1 groups are identical or different, and form, together, a hydrocarbon-based ring or a heterocycle,
• R2, R3, R4, R5 and R6, independently of one another, are chosen from the group consisting of hydrogen atom, halogen atoms chosen from the group consisting of chlorine, fluorine and bromine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituents groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), —(CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk, and —(CH2)m—NRkR1, with Rk, R1, Rm and m as defined above,
• or R4, R5 and R6 form, in pairs, one or more hydrocarbon-based ring(s) or heterocycle(s), with at least one of the R4, R5 and R6 groups representing a hydrogen atom,
• X is chosen from the group consisting of O, NR9, S, S(O), SO2, SO2NR9, and R8 and R9 are each, independently of one another, chosen from the group consisting of hydrogen atom, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, alkaryl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, and polymer chains, optionally substituted,
• or R8 and R9 form, together with the atom to which they are attached, a heterocycle from at least one compound of general formula (IVB)
• in which:
• R1, R4, R5, R6, R8, X and n are as defined above, and
• R2a represents a group chosen from the group consisting of hydrogen atom, halogen atoms, alkyl groups, haloalkyl groups, acyl groups, aryl groups, arylalkyl groups, hydrocarbon-based rings, heterocycles, polymer chains and groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), (CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk and —(CH2)m—NRkR1, in which Rk, R1, Rm and m are as defined above,
• wherein the method comprises at least stages a′-c′:
• a′—converting said compound of general formula (IVB) into at least its oxime derivative of general formula (VB)
• in which:
• R1, R2a, R4, R5, R6, R8, X and n are as defined above,
• b′—converting said compound of general formula (VB), by Beckmann rearrangement and consecutive reduction(s), into at least said compound of general formula (IB), and
• c′—recovering said compound of general formula (IB).

A compound of general formula (IA)

• in which:
• R1 is chosen from the group consisting of halogen atoms chosen from the group consisting of chlorine, fluorine, bromine and iodine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituent groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), —(CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk, and —(CH2)m—NRkR1, and:
• Rk, R1 and Rm are each independently chosen from the group consisting of hydrogen atom, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, and heterocycles,
• or Rk and R1 form, together with the atom to which they are attached, a heterocycle,
• with m denoting an integer greater than or equal to 0,
• R2, R3, R4, R5 and R6 independently of one another, are chosen from the group consisting of hydrogen atom, halogen atoms chosen from the group consisting of chlorine, fluorine and bromine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituent groups chosen from the group consisting of —(CH2)mORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), —(CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk, and —(CH2)m—NRkR1, with Rk, R1, Rm and m as defined above,
• or R4, R5 and R6 form, in pairs, one or more hydrocarbon-based ring(s) or heterocycle(s), with at least one of the R4, R5 and R6 groups representing a hydrogen atom,
• R7=—XR8, where X is chosen from the group consisting of O, NR9, S, S(O), SO2, SO2NR9, and R8 and R9 are each, independently of one another, chosen from the group consisting of hydrogen atom, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, alkaryl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, and polymer chain, optionally substituted,
• or R8 and R9 form, together with the atom to which they are attached, a heterocycle from at least one compound of general formula (IVB)
• in which:
• R1, R4, R5, R6, R8, X and n are as defined above, and
• R2a represents a group chosen from the group consisting of hydrogen atom, halogen atoms, alkyl groups, haloalkyl groups, acyl groups, aryl groups, arylalkyl groups, hydrocarbon-based rings, heterocycles, polymer chains and groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), (CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk and —(CH2)m—NRkR1, in which Rk, R1, Rm and m are as defined above, and n=1.

A compound of general formula (VB)

• in which:
• R1 is chosen from the group consisting of halogen atoms chosen from the group consisting of chlorine, fluorine, bromine and iodine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituent groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), —(CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk and —(CH2)m—NRkR1, and:
• Rk, R1 and Rm each independently chosen from the group consisting of hydrogen atom, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, or Rk and R1 form, together with the atom to which they are attached, a heterocycle, with m denoting an integer greater than or equal to 0,
• R4, R5 and R6 independently of one another, are chosen from the group consisting of hydrogen atom, halogen atoms chosen from the group consisting of chlorine, fluorine and bromine, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, polymer chains, and substituents groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), —(CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk, and —(CH2)m—NRkR1, with Rk, R1, Rm and m as defined above, or R4, R5 and R6 form, in pairs, one or more hydrocarbon-based ring(s) or heterocycle(s), with at least one of the R4, R5 and R6 groups representing a hydrogen atom,
• R2a represents a group chosen from the group consisting of hydrogen atoms, halogen atoms, alkyl groups, haloalkyl groups, acyl groups, aryl groups, arylalkyl groups, hydrocarbon-based rings, heterocycles, polymer chains and groups chosen from the group consisting of —(CH2)m—ORk, —CH(ORk)(OR1), —(CH2)m—SRk, —(CH2)m—S(O)Rk, —(CH2)m—SO2Rk, —(CH2)m—SO2NRkR1, —(CH2)m—SO3Rk, —(CH2)m—NO2, —(CH2)m—CN, —(CH2)m—PO(ORk)(OR1), (CH2)m—SiRkR1Rm, —(CH2)m—COORk, —(CH2)m—NCORk and —(CH2)m—NRkR1, in which Rk, R1, Rm and m are as defined above,
• X is chosen from the group consisting of O, NR9, S, S(O), SO2, SO2NR9, and R8 and R9 are each, independently of one another, chosen from the group consisting of hydrogen atoms, alkyl groups, haloalkyl groups, alkenyl groups, alkynyl groups, acyl groups, aryl groups, arylalkyl groups, alkaryl groups, arylalkenyl groups, arylalkynyl groups, hydrocarbon-based rings, heterocycles, and polymer chains, optionally substituted,
• or R8 and R9 form, together with the atom to which they are attached, a heterocycle from at least one compound of general formula (IVB)
• in which:
• R1, R2a, R4, R5, R6, R8, X and n are as defined above.