[go: up one dir, main page]

WO2007013681A1 - Compose guanidine-thio-uree et procede de fabrication d'un alcool nitro utilisant ce compose - Google Patents

Compose guanidine-thio-uree et procede de fabrication d'un alcool nitro utilisant ce compose Download PDF

Info

Publication number
WO2007013681A1
WO2007013681A1 PCT/JP2006/315364 JP2006315364W WO2007013681A1 WO 2007013681 A1 WO2007013681 A1 WO 2007013681A1 JP 2006315364 W JP2006315364 W JP 2006315364W WO 2007013681 A1 WO2007013681 A1 WO 2007013681A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
alkyl
hydrogen atom
branched
substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2006/315364
Other languages
English (en)
Japanese (ja)
Inventor
Kazuo Nagasawa
Masaya Ikunaka
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nagase and Co Ltd
Tokyo University of Agriculture and Technology NUC
Tokyo University of Agriculture
Original Assignee
Nagase and Co Ltd
Tokyo University of Agriculture and Technology NUC
Tokyo University of Agriculture
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nagase and Co Ltd, Tokyo University of Agriculture and Technology NUC, Tokyo University of Agriculture filed Critical Nagase and Co Ltd
Priority to JP2007526948A priority Critical patent/JP4775915B2/ja
Publication of WO2007013681A1 publication Critical patent/WO2007013681A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
    • B01J31/1875—Phosphinites (R2P(OR), their isomeric phosphine oxides (R3P=O) and RO-substitution derivatives thereof)
    • B01J31/188—Amide derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses

Definitions

  • guanidine compounds have a problem that the optical purity of the obtained substance is low (for example, 20% ee to 50% ee).
  • diastereoselective Henry reactions are known to have chiral aliphatic guanidines that catalyze the highly selective addition of nitromethane to amino acid-derived aldehydes (eg, D. Ma et al., Angewante Chemie). International Edition, Vol. 43, 2002, p. 9401-9403).
  • R 1 and R 2 are each independently
  • R 7 and R 8 are each independently a hydrogen atom or a Cj Cs alkyl group
  • R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is a C 1 -C 5 alkyl group or aryl group which may be branched
  • R 7 is a hydrogen atom or a 5 alkyl group
  • R 9 is a C 1 -C 5 alkyl group or aryl group which may be branched
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • (i) may be substituted with halogen atoms, and / or may form a branched or cyclic, C 1 -C 5 alkyl group;
  • an aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a halogen atom, and / or may form a branch or a ring. 5 alkyl groups,
  • Roh or branched or cyclic may be the to form Ji ⁇ Ji 5 alkoxy group
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • a ci to c 5 alkyl group that may be substituted with a haguchigen atom and / or may form a branch or a ring,
  • a Ci Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each independently substituted with a halogen atom and / or optionally branched or ring-formed) Independently, a hydrogen atom or a Ci Cs alkyl group), a nitro group, a strong rubamoyl group, N— (Ci Cs alkyl) carbamoyl group; an N, N—di (C 1 -C 5 alkyl) force rubamoyl group , or a NR 7 COR 9 (where, R 7 is a hydrogen atom or Ji ⁇ Ji 5 alkyl group, and R 9 is optionally branched C I ⁇ C also be 5 alkyl group or Ariru group der Which may be substituted with an aryl group,
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group),
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or aryl group), and Halogen atom
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • R 5 and R 6 are each independently
  • (ii) may be substituted with a halogen atom, and Z or may form a branched or cyclic alkyl group of C 1 -C 20;
  • Ci Cg alkoxy group which may be branched
  • R 31 (where 1 3 () and 1 31 are each independently a hydrogen atom or
  • Nitro group strong rubamoyl group, N— (C Cg alkyl) carbamoyl group, N, N—di (C 1 -C 5 alkyl) strong rubamoyl group, or one NR 7 COR 9
  • R 7 is a hydrogen atom or a C 1 -C 5 alkyl group
  • R 9 is an optionally branched Ci C 5 alkyl group or aryl group.
  • Aryl group
  • R 3 and R 31 are each independently a hydrogen atom or a Ci C 5 alkyl group
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • R 31 (wherein, R 3. And R 31 are each independently hydrogen atom or a Ci C 5 alkyl group), a nitro group, Karupamoiru group, N-(Ci Cs alkyl Le) force Rubamoiru group, N , N-di (Ci Cs alkyl) carbamoyl group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 may be branched).
  • 5 is an alkyl group or an aryl group), an aryl group,
  • R 3 ° and R 31 are each independently a hydrogen atom or a Ci Cs alkyl group
  • N-alkyl) carbamoyl group TJP2006 / 315364
  • a heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Ci Cs alkyl group which may be substituted with a halogen atom and / or may form a branch or a ring,
  • Ci Cs alkoxy group which may be substituted with a haguchi atom and / or may form a branch or a ring,
  • Ci Cs alkyl group Cyan group, which may be substituted with a divalent atom and / or may be branched or branched to form a ring — — NR 7 R 8 (where R 7 and R 8 Are each independently a hydrogen atom or a C Cs alkyl group), a nitro group, a carpamoyl group, an N— (Ci Cs alkyl) force rubermoyl group, an N, N—di (Ci Cs alkyl) force ruber moyl group, Or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched 5 alkyl group or aryl group).
  • R 7 and R 8 Are each independently a hydrogen atom or a C Cs alkyl group), a nitro group, a carpamoyl group, an N— (Ci Cs alkyl) force rubermoyl group
  • NR 7 R 8 (wherein, R 7 and R 8 are each independently hydrogen atom or a C 1 -C 5 alkyl group),
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or Ci to C 5 alkyl group, and R 9 is an optionally branched 5 alkyl group or aryl group), and
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • a C 1 -C 5 alkyl group which may be substituted with a halogen atom and which may form a no or branched or ring;
  • NR 7 R 8 May be substituted with a halogen atom, and Z or branched or rings formed by C 1 optionally -C 5 alkyl group, Shiano group, one NR 7 R 8 (wherein, R 7 and R 8, each independently a hydrogen atom or a C 1 -C 5 alkyl group), a nitro group, Karupamoiru group, N- (C 1 ⁇ C 5 alkyl) Karupamo I le group, N, N-di (C 1 -C 5 alkyl) rubamoyl group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 may be branched C 1 -C An aryl group, which may be substituted with an alkyl group or an aryl group),
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group),
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • R 5 and R 6 together represent a divalent group represented by: 1 (CH 2 ) m — where m is an integer from 2 to 8, and
  • X is a halide anion
  • the compound of formula (I) above has the following formula (1 ′) or (I ′′):
  • R 1 and R 2 in the above formula (1,) or (1 ") may each independently be substituted with a halogen atom and form Z or a branch or ring It is an aryl group substituted with an alkyl group.
  • R 3 and R 4 in formula (1 ′) or (′.) Above are each independently be substituted with a halogen atom and form Z or a branch or ring It is an aryl group substituted with an alkyl group.
  • R 3 and R 4 in formula (1 ′) or (′.) Above are each independently
  • an aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a halogen atom, and Z or a 5 alkyl group which may form a branch or a ring,
  • a 5- alkoxy group which may be substituted with a haguchigen atom and / or which may form a branch or a ring,
  • R 7 is a hydrogen atom or a C Cs alkyl group
  • R 9 is an optionally branched 5 alkyl group or aryl group.
  • aryl group optionally substituted, aryl group,
  • R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group
  • NR 7 C ⁇ R 9 (wherein R 7 is a hydrogen atom or a Ci Cs alkyl group, and R 9 is an optionally branched C Cs alkyl group or alkyl Group), and
  • An aralkyl group which may be substituted with at least one group selected from the group consisting of:
  • R 5 and R 6 in the above formula (1,) or (1 ") are each independently
  • Ci C ⁇ alkyl group which may form a branch or ring
  • a C 1 -C 5 alkyl group which may be substituted with a haguchigen atom, and / or which may form a branch or a ring,
  • a C 1 -C 5 alkoxy group that may be substituted with a haguchigen atom, and / or may form a branch or ring,
  • a Ci Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are Each independently a hydrogen atom or a C i Cs alkyl group), nitro group, carpamoyl group, N— (C 1 -C 5 alkyl) carpamoyl group, N, N—di (C 1 -C 5 alkyl) Carpamoyl group, or one NR 7 COR 9 (where R 7 is a hydrogen atom or the same 5- alkyl group, and R 9 is an optionally branched 5- alkyl group or aryl group. ) May be substituted with an aryl group,
  • NR 7 R 8 (wherein, R 7 and R 8 are each independently hydrogen atom or a C 1 -C 5 alkyl group),
  • R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched Ci to C 5 alkyl group or aryl group
  • R 7 is a hydrogen atom or a 5 alkyl group
  • R 9 is an optionally branched Ci to C 5 alkyl group or aryl group
  • R 5 and R 6 together represent a divalent group represented by 1 (CH 2 ) m — (where m is an integer from 2 to 8).
  • the present invention also provides a process for the preparation of a guazin monothiourea compound comprising the following formulas (I I) and (I I ′):
  • reaction intermediate (a 1) A step of reacting at least one amine selected from the group consisting of compounds represented by the following formula with carbon disulfide in a solvent (A) to obtain a reaction intermediate (a 1);
  • reaction intermediate (a 1) can be converted into Hg (II) salt (HgX 2 ) or 1 [3- (dimethylamino) propyl] 1 3-ethyl carpositimide hydrochloride (EDC) in the solvent (B).
  • Hg (II) salt HgX 2
  • EDC 3-ethyl carpositimide hydrochloride
  • R 3 and R 4 are each independently
  • a c 1 -c 5 alkyl group which may be substituted with a halogene atom and / or may form a branch or a ring,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • the method further comprises, after removing the protecting groups Y and / or Y, of the reaction intermediate (b 1), the following formulas (I V) and (I V):
  • R 1 and R 2 are each independently an aryl group, wherein the aryl group is
  • Ci Cs alkoxy group which may be substituted with a haguchi atom and / or may form a branch or a ring,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or Ci Cs alkyl group, and R 9 is an optionally branched 5 alkyl group or aryl group
  • R 7 is a hydrogen atom or Ci Cs alkyl group
  • R 9 is an optionally branched 5 alkyl group or aryl group
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • the present invention also provides a process for producing a guanidine monothiorea compound comprising the following formulas (II) and (I):
  • a process for producing a guanidine monothiorea compound comprising the following formulas (II) and (I):
  • the solvent (C) at least one amine selected from the group consisting of compounds represented by the following formula (V):
  • reaction intermediate (a 2) is reacted with at least one amine selected from the group consisting of the formula (II) and (11,) in the solvent (D) to give a reaction intermediate (b 2) Obtaining
  • Y and Y ′ are each independently a protecting group
  • R 3 and R 4 are each independently
  • Ci Cs alkyl group which may be substituted with a halogen atom, and may form a no or branched or ring;
  • aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a halogen atom, and / or a 5- alkyl group which may form a branch or a ring,
  • a C 1 -C 5 alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and Each R 8 is independently a hydrogen atom or a C 1 -C 5 alkyl group), a nitro group, a carbamoyl group, an N- (C 1 -C 5 alkyl) carbamoyl group, an N, N-di ( C 1 -C 5 alkyl) Carpamoyl group, or one NR 7 COR 9 (where R 7 is a hydrogen atom or a 5 alkyl group, and R 9 may be branched Ci Cs alkyl group or aryl group) An aryl group, which may be substituted with
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Cz C 5 alkyl group or aryl group) , and
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • C port Gen atoms May be substituted by C port Gen atoms, and / or optionally branched or form a cyclic C 1 -C 5 alkoxy group,
  • a halogen atom May be substituted with a halogen atom, and Z or branched or rings formed by C 1 optionally -C 5 alkyl group, Shiano group, one NR 7 R 8 (wherein, R 7 and R 8, each independently a hydrogen atom or a C 1 -C 5 alkyl Le group), a nitro group, Karupamoiru group, N- (C 1 ⁇ C 5 alkyl) Cal Pamoiru group; N, N-di (C 1 -C 5 alkyl) carbamoyl group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched 5 alkyl group or an aryl group).
  • aryl group optionally substituted, aryl group,
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group), PT / JP2006 / 315364
  • R 11 is an aryl group
  • Ci Cs alkyl group which may be substituted with a halogen atom and may form a no or branched or ring;
  • a 5 alkoxy group optionally substituted with a halogen atom and / or optionally forming a branch or ring,
  • a Ci Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are Each independently a hydrogen atom or a Ci Cs alkyl group), a nitro group, a carbamoyl group, N— (C 1 -C 5 alkyl) a carbamoyl group, N, N—di (C 1 -C 5 alkyl) Carpamoyl group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C Cs alkyl group, and R 9 is a C 1 -C 5 alkyl group or aryl group which may be branched) Which may be substituted with an aryl group,
  • NR 7 R 8 (wherein, R 7 and R 8 are each independently hydrogen atom or a C 1 -C 5 alkyl group), Nitro group,
  • An aryl group that may be substituted with at least one group selected from the group consisting of:
  • the method further comprises the following formulas (I V) and (IV,) after removing the protecting groups Y and / or Y ′ of the reaction intermediate (b 2):
  • R 1 and R 2 are each independently an aryl group, wherein the aryl group is
  • a 5- alkyl group which may be substituted with a haguchigen atom and which may form Z or a branched or ring;
  • a 5 alkoxy group which may be substituted with a halogen atom, and / or may form a branch or a ring,
  • NR 7 R 8 (wherein, R 7 and R 8 are each independently hydrogen atom or a C 1 -C 5 alkyl group),
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • the present invention also provides a compound represented by the following formula (VI): Provide
  • Y and Y are each independently a protecting group
  • R 3 and R 4 are each independently
  • Ci Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are Independently a hydrogen atom or a C 1 -C 5 alkyl group), a nitro group, a strong rubamoyl group, an N_ (Ci Cs alkyl) carbamoyl group, an N, N-di (Ci Cs alkyl) carbamoyl group, or 1 NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched C 1 to C 5 alkyl group or an aryl group).
  • R 7 is a hydrogen atom or a 5 alkyl group
  • R 9 is an optionally branched C 1 to C 5 alkyl group or an aryl group.
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • a C 1 -C 5 alkyl group which may be substituted with a halogene atom and / or which may form a branch or ring,
  • Z or branched or cyclic may be the to form Ji ⁇ Ji 5 alkoxy group
  • a C Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each independently substituted with a halogen atom and / or may form a branch or ring) Independently a hydrogen atom or a C 1 -C 5 alkyl group), an etro group, a strong rubamoyl group, an N— (C Cs alkyl) carbamoyl group; an N, N—di (C 5 -C 5 alkyl) carbamoyl group A group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or the same 5- alkyl group, and R 9 is an optionally branched Ci C 5 alkyl group or an aryl group) Optionally substituted with an aryl group,
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group),
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched 5 alkyl group or an aryl group), and
  • the compound of the above formula (V I) has the following formula (V I ') or (V I ")
  • the present invention also provides a process for producing a compound represented by the above formula (VI), which comprises the following formulas (II) and (II ′): ( 1 ! ′) A step of reacting at least one amine selected from the group consisting of the compounds represented by the following with carbon disulfide in a solvent (A);
  • Y and Y ′ are each independently a protecting group
  • R 3 and R 4 are each independently
  • Ci Cs alkyl group which may be substituted with a halogen atom and / or may form a branch or a ring;
  • an aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a halogen atom, and Z or a C Cs alkyl group which may form a branch or a ring,
  • Ci C 5 alkoxy group May be substituted with a haguchigen atom and / or branched or ring Ci C 5 alkoxy group, which may form
  • R 7 is a hydrogen atom or a C 1 -C 5 alkyl group
  • R 9 is an optionally branched 5 alkyl group or aryl group.
  • aryl group optionally substituted, aryl group,
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group),
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is a C 1 -C 5 alkyl group or an aryl group which may be branched), and
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • a C Cs alkyl group which may be substituted with a halogen atom and / or which may form a branch or ring,
  • a C Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each independently substituted and optionally substituted with a halogen atom and / or may form a branch or ring)
  • one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched 5 alkyl group or aryl group) May have been, allyl group,
  • NR 7 COR 9 (where R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci-C 5 alkyl group or aryl group) ) , and
  • Ci Cg alkyl group which may be substituted with a halogen atom and / or may form a branch or a ring;
  • an aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a vacant atom, and Z or a C i to C 5 alkyl group which may form a branch or a ring ,
  • a 5- alkoxy group which may be substituted with a haguchigen atom and / or which may form a branch or a ring,
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group),
  • R 7 is a hydrogen atom or Ci Cs alkyl PT / JP2006 / 315364
  • a 34 radical and R 9 is branched ⁇ Ji may ⁇ Ji 5 alkyl group or ⁇ Li Lumpur group), and
  • alkanoleno group optionally substituted with at least one group selected from the group consisting of:
  • a 5- alkyl group which may be substituted with a haguchigen atom and / or may form a branch or a ring,
  • a C Cs alkoxy group which may be substituted with a halogen atom and / or may form a branch or a ring,
  • R 7 and R 8 are each Independently a hydrogen atom or a C Cs alkyl group), a nitro group, a carbamoyl group, an N— (Ci Cs alkyl) carbamoyl group; an N, N—di (C 1 -C 5 alkyl) carbamoyl group, or
  • R 7 COR 9 wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or aryl group). You may have an ariel group,
  • R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group
  • R 7 is a hydrogen atom or ⁇ , ⁇ 5 alkyl 06315364
  • R 9 is an optionally branched Ci Cs alkyl group or aryl group
  • R 11 is an aryl group
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 9 is an optionally branched 5 alkyl or aryl group
  • An aryl group that may be substituted with at least one group selected from the group consisting of:
  • the compound of the above formula (V I I) has the following formula (V I I
  • the present invention also provides a process for producing a compound represented by the above formula (VII), which comprises the following formula (II):
  • Ararukiru a group may Ariru portions constituting the optionally substituted with a halogen atom, and Z or branched or cyclic may be the to form Ji ⁇ Ji 5 alkyl group, A Ci Cs alkoxy group which may be substituted with a halogen atom and which may form z or a branched or ring,
  • a C 1 -C 5 alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are Each independently a hydrogen atom or a Ci Cs alkyl group), a nitro group, a carbamoyl group, an N- (C Cg alkyl) carbamoyl group, an N, N-di (C 1 -C 5 alkyl) carbamoyl group , Or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a Ci Cs alkyl group, and R 9 is an optionally branched Ci Cg alkyl group or an aryl group).
  • R 7 and R 8 are Each independently a hydrogen atom or a Ci Cs alkyl group), a nitro group, a carbamoyl group, an N- (C Cg alkyl) carbamoyl group, an N, N-di (C 1 -C 5 alkyl) carbamoyl group , Or one NR
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Ci c 5 alkyl group which may be substituted with a halogen atom and which may form Z or a branched or ring; 5 to 5 alkoxy groups which may be substituted with a haguchi atom and / or may form a branch or a ring,
  • NR 7 R 8 (wherein, R 7 and R 8, Each independently a hydrogen atom or C Cs alkyl group), nitro group, carbamoyl group, N— (Ci Cg alkyl) carbamoyl group; N, N—di (C 1 -C 5 alkyl) carbamoyl group, Or one substituted with NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or aryl group) May have been, allyl group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or a C Cs alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or an aryl group), and
  • R 11 is an aryl group
  • a Ci c 5 alkoxy group which may be substituted with a halogene atom and which may form Z or a branched or ring;
  • NR 7 R 8 (wherein, R 7 and R 8 are each independently hydrogen atom or a C 1 -C 5 alkyl group),
  • R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or aryl group
  • R 7 is a hydrogen atom or a C 1 -C 5 alkyl group
  • R 9 is an optionally branched Ci Cs alkyl group or aryl group
  • An aryl group that may be substituted with at least one group selected from the group consisting of:
  • the present invention also provides a method for producing an optically active nitro alcohol compound, which method comprises:
  • (i) may form a branch or a ring; An alkyl group;
  • an aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a halogen atom, and / or a C Cs alkyl group which may form a branch or a ring,
  • Ci Cs alkoxy group which may be substituted with a halogen atom and / or may form a branch or a ring,
  • R 7 and R 8 are each Independently a hydrogen atom or a C 1 -C 5 alkyl group), a utro group, a carbamoyl group, N— (C 1 -C 5 alkyl) carbamoyl group, N, N—di (C 1 -C 5 Alkyl) carbamoyl group, or —NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 may be branched C 1 -C 5 alkyl group or An aryl group) which may be substituted with an aryl group,
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group),
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • a C 1 -C 5 alkyl group which may be substituted with a halogene atom and / or which may form a branch or ring,
  • a C 1 -C 5 alkoxy group which may be substituted with a halogen atom and which may form Z or a branched or ring;
  • a C 1 -C 5 alkyl group, a cyano group, one NR 7 R 8 (where R 7 and R 8 They are each independently hydrogen atom or a C 1 -C 5 alkyl Le group), a nitro group, Karupamoiru group, N_ (C 1 ⁇ C 5 alkyl) Cal Pamoiru group; N, N-di (C 1 ⁇ C 5 alkyl) carbamoyl group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 may be branched C 1 -C 5 alkyl group or aryl group) An aryl group, which may be substituted with
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group),
  • R 7 is a hydrogen atom or a C Cs alkyl group, and R 9 may be branched C, C 5 alkyl group or alkyl Group
  • R 7 is a hydrogen atom or a C Cs alkyl group, and R 9 may be branched C, C 5 alkyl group or alkyl Group
  • a guanidine monourea compound that can function effectively as an organic catalyst in the Henry reaction is provided. Since the guanidine monothiorea compound of the present invention does not contain a metal species in its structure, it has less environmental impact and can be used as a safer material in industrial production. Further, the guanidine monothiorea compound of the present invention can be produced through a simple process without requiring a complicated reaction operation. Furthermore, the guanidine monothiorea compound of the present invention can produce a desired utroalcohol compound with excellent optical purity and yield through a Henry reaction. BEST MODE FOR CARRYING OUT THE INVENTION
  • CC n alkyl group which may form a branch or a ring is any linear alkyl group having 1 to n carbon atoms, and any branched alkyl group having 3 to n carbon atoms. And any cyclic alkyl group having 3 to n carbon atoms.
  • CC s alkyl group which may form a branch or a ring includes methyl, ethyl, n-propyl, isopropyl, cyclopropinole, n-putinole, sec-peptinole, tert-butinole, cyclopeptinole, Examples include pentyl and cyclopentyl.
  • Alkyl group includes n-heptyl, isoheptyl, n _ octyl, , N—de JP2006 / 315364
  • alkyl groups such as 43 sil, n-dodecyl, mono-C 8 H 17 , mono-C 18 H 37 .
  • the term “optionally substituted with a halogen atom and / or n or an alkyl group which may form a branch or a ring” is unsubstituted, or at least Examples thereof include Ci Cn alkyl groups in which one hydrogen atom is substituted with a halogen atom and may form the above-mentioned branched or ring.
  • C 1 -C n alkoxy group which may form a branch or a ring means any linear alkoxy group having 1 to n carbon atoms, any C 3 to n carbon atoms It includes a branched alkoxy group and any cyclic alkoxy group having 3 to n carbon atoms.
  • an optionally branched or ring-formed C 5 alkoxy group includes methyloxy, ethyloxy, n-propyloxy, isopropyloxy, cyclopropyloxy, sec-ptyloxy, tert-pentyloxy.
  • C 1 -C 5 arnolequinole is a C to C 5 linear alkyl group. or means a branched alkyl group of C 3 ⁇ C 5.
  • alkenyl group of c 2 to c n which may form a branch or a ring
  • any straight chain alkenyl group having 2 to 20 carbon atoms includes ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-propyl.
  • C 2 -C n alkenyl group which may be substituted with a halogen atom and / or may form a branch or a ring means an unsubstituted or a small amount Kutomo one hydrogen atom is substituted with a halogen atom and a good c 2 to c n alkenyl group optionally form form the branched or cyclic.
  • alkynyl group of c 2 to c n which may form a branch or a ring
  • n is an integer
  • alkynyl group having 2 to 20 carbon atoms etul, 1-propynyl, 2-probule, 1-puchur, 2-butininore, 1-pentinole, 1-hexinole, 1 1-octynyl, 1-octynyl, 1-decynyl, 1-dodecynyl and the like, and as an arbitrary branched alkynyl group having 3 to 20 carbon atoms, 1-methyl-2-probule and the like are mentioned.
  • the cyclic alkynyl group having 3 to 20 carbon atoms include cyclopropyl ether, cycloptyl etynyl and the like.
  • C 2 -C n alkyl group which may be substituted with a halogen atom and may form a Z or branched or ring (where n is an integer) is an unsubstituted, There is at least one hydrogen atom is substituted with a halogen atom, the branch or include good C 2 -C n alkynyl group which may form a ring.
  • examples of the term “aralkyl group” include benzyl, phenethyl, and naphthylmethyl.
  • heteroarylkyl group examples include pyridylmethyl, indolylmethyl, furylmethyl, cenylmethyl, and pyrrolylmethyl.
  • aryl group examples include phenyl, naphthyl, anthryl, phenanthryl and the like.
  • heteroaryl group examples include pyridyl, pyrrolyl, imidazolyl, furyl, indolyl, benzothiophene-2-yl, chenore, oxazolinole, thiazolinole, 3,4-methylenedioxyphe- / Le, 3,4-ethylenedioxyphenyl, and tetrazolyl.
  • examples of the term “halogen atom” include chlorine atom, bromine atom, iodine atom and fluorine atom.
  • halide anion means a halogen ion, and includes a chloride ion, a bromide ion, an iodide ion, and a fluoride ion.
  • the guanidine monourea compound of the present invention includes, for example, the following formula (I):
  • R 1 and R 2 are each independently An aryl group, wherein the aryl group is
  • Ci Cs alkyl group which may be substituted with a halogen atom and may form Z or a branched or ring,
  • Ci Cs alkoxy group which may be substituted with a haguchigen atom and / or which may form a branch or a ring;
  • Ci. C alkyl group, cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each independently A hydrogen atom or a C 1 -C 5 alkyl group), a nitro group, a carbamoyl group, an N- (C Cs alkyl) carbamoyl group, an N, N-di (C 1 -C 5 alkyl) carbamoyl group Or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or an aryl group. ) May be substituted with an aryl group,
  • NR 7 R 8 (wherein, R 7 and R 8 are each independently hydrogen atom or a C 1 -C 5 alkyl group),
  • R 7 is a hydrogen atom or a 5 alkyl group
  • R 9 is an optionally branched 5 alkyl group or an aryl group
  • An aryl group optionally substituted with at least one group selected from the group consisting of: 2006/315364
  • R 3 and R 4 are each independently
  • (i) may be substituted with a halogen atom, and Z or may form a branched or cyclic, C 1 -C 5 alkyl group;
  • Ararukiru a group may Ariru portions constituting the optionally substituted with C port Gen atoms, and Roh or branched or rings formed have may ⁇ ⁇ 5 alkyl group,
  • Ci Cs alkoxy group which may be substituted with a halogen atom, and may form a ⁇ or branched or ring,
  • aryl group optionally substituted, aryl group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • a c 1 -c 5 alkyl group which may be substituted with a halogen atom and / or may form a branch or ring,
  • a 5- alkoxy group which may be substituted with a haguchigen atom and / or which may form a branch or a ring,
  • Ci Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each substituted with a halogen atom and / or may form a branch or ring) Independently hydrogen atom or Ci Cs alkyl group), nitro group, carbamoyl group, N— (C Cs alkyl) carbamoyl group; N, N—di (C 1 -C 5 alkyl) force rubermoyl group, Or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched C 1 to C 5 alkyl group or an aryl group). You may have an ariel group,
  • R 7 and R 8 are each independently a hydrogen atom or a Ci Cs alkyl group
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • R 5 and R 6 are each independently
  • (ii) may be substituted with a halogen atom and / or may form a branch or ring,
  • Ci Ci to C 5 alkyl group which may be branched
  • C 1 -C 5 alkyl group which may be branched, Cyan group, one NR 30 R 31 (where 3 ° C 1 ⁇ 31 is independently a hydrogen atom or
  • Nitro group carbamoyl group, N— (C 1 -C 5 alkynole) carbamoyl group, N, N—di (C 1 -C 5 alkyl) carbamoyl group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a Ci Cs alkyl group, and R 9 is a 5 alkyl group or an aryl group which may be branched), an aryl group,
  • R 3 and R 31 are each independently a hydrogen atom or a C, to C 5 alkyl group), Nitro group,
  • R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched 5 alkyl group or aryl group), and.
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Ci Cs alkyl group which may be branched
  • R 3Q and R 31 are each independently a hydrogen atom or a Ci C 5 alkyl group), a nitro group, a carbamoyl group, N— (C 1 -C 5 alkyl), a force rubamoyl group, N , N-di (Ci Cs alkyl) carbamoyl group or one NR 7 COR 9 (where R 7 is a hydrogen atom or a 5 alkyl group, and R 9 may be branched Ci Cg alkyl) Group or aryl group), an aryl group,
  • R 30 and R 31 are each independently a hydrogen atom or a c 1 -c 5 alkyl group
  • Carpamoyl group N— (C 1 -C 5 alkyl) carpamoinole group,
  • R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched C Cs alkyl group or an aryl group), and
  • a heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
  • a 5- alkyl group which may be substituted with a halogen atom, and / or may form a branch or a ring,
  • a C 1 -C 5 alkoxy group which may be substituted with a halogen atom, and may form a no or branched or ring;
  • C may be substituted with a C atom atom, and may be branched by forming a ring or a ring, or a C Cs alkyl group, a cyano group, _NR 7 R 8 (where R 7 and R 8 Each independently represents a hydrogen atom or a Ci Cs alkyl group), a nitro group, a carpamoyl group, an N— (C 1 to C 5 alkyl) force / levermoyl group, an N, N—di (C 1 to C 5 alkyl) a strong rubamoyl group, or one NR 7 COR 9 (wherein R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched C 1 -C 5 alkyl group or Aryl groups), aryl groups, which may be substituted with
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • Carpamoyl group N— (C 1 -C 5 alkyl) carbamoyl group,
  • R 7 is a hydrogen atom or Ci Cs alkyl group, and R 9 is an optionally branched 5 to 5 alkyl group or aryl group
  • R 9 is an optionally branched 5 to 5 alkyl group or aryl group
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • Ci Cg alkoxy group which may be substituted with a halogen atom and / or may form a branch or a ring,
  • R 7 and R 8 are each independently a hydrogen atom or a Ci Cg alkyl group
  • R 7 is a hydrogen atom or Ci Cs alkyl group, and R 9 is a C 1 -C 5 alkyl group or aryl group which may be branched
  • R 7 is a hydrogen atom or Ci Cs alkyl group
  • R 9 is a C 1 -C 5 alkyl group or aryl group which may be branched
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • R 5 and R 6 together represent a divalent group represented by: 1 (CH 2 ) m ⁇ , where m is an integer from 2 to 8, and
  • X— is a halide anion
  • the guanidine monothiorea compound of the formula (I) of the present invention has an asymmetric center at the carbon atom to which the R 3 group and R 4 group are respectively bonded.
  • the guanidine monourea compound of formula (I) of the present invention has the following structure:
  • It preferably has a structure represented by
  • R and R 2 may each independently be substituted with a halogen atom, 15364
  • R 3 and R 4 are each independently
  • (i) may be substituted with halogen atoms, and / or it may also form a branched or cyclic Le ,, C 1 -C 5 alkyl group; or
  • a C 1 -C 5 alkyl group, a cyano group, one NR 7 R 8 (where R 7 and R 8 Each independently is an elementary atom or a Ci Cs alkyl group), a nitro group, a force rubamoyl group, an N— (Ci Cs alkyl) carbamoyl group, an N, N—di (C 1 -C 5 alkyl) Or NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched 5 alkyl group or an aryl group) ) May be substituted with an aryl group,
  • R 7 and R 8 are each independently a hydrogen atom or a Ci Cg alkyl group
  • N, N—di (C 1 -C 5 alkyl) force rubamoyl group NR 7 COR 9 (wherein R 7 is a hydrogen atom or a Ci Cs alkyl group, and R 9 is an optionally branched 5 alkyl group or an aryl group), and
  • an aralkyl group which may be substituted with at least one group selected from the group consisting of:
  • R 5 and R 6 are each independently
  • (ii) may form a branch or a ring, An alkyl group
  • a C Cs alkyl group which may be substituted with a halogen atom and / or may form a branch or ring,
  • An alkyl group, a cyano group, one NR 7 R 8 (where R 7 and Each R 8 is independently a hydrogen atom or a C 1 -C 5 alkyl group), a nitro group, a carbamoyl group, an N— (C Cs alkyl) force rubamoyl group, an N, N—di (C 1- C 5 alkyl) carbamoyl group, or one NR 7 COR g (where R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and; R 9 may be branched C 1- A C 5 alkyl group or an aryl group), an aryl group,
  • NR 7 R 8 (where R 7 and R 8 are each independently a hydrogen atom Or C 1 -C 5 alkyl group),
  • R 7 is a hydrogen atom or a C 1 to C 5 alkyl group, and R 9 is an optionally branched 5 to 5 alkyl group or aryl group), and
  • R 5 and R 6 together are preferably a compound that represents a divalent group represented by 1 (CH 2 ) m — (where m is an integer of 2 to 8).
  • the guanidine monothiourea compound can be easily produced, for example, by using one of the following two methods.
  • reaction intermediate (al) is generated by reacting at least one amine selected from the group consisting of the compounds represented by the following formula with carbon disulfide in a solvent ( ⁇ ).
  • An amine represented by formula (II) and an amine represented by formula (I) May be the same or different.
  • Y and Y ′ each independently represent tert-ptoxycarboninole (Boc), 9-fluorenylmethoxycarbonyl (Fmo c), etc.
  • a protecting group and
  • R 3 and R 4 are each independently
  • Ci Cs alkyl group which may be substituted with a halogen atom and / or may form a branch or a ring;
  • an aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a halogen atom, and Z or a 5 alkyl group which may form a branch or a ring,
  • a C 1 -C 5 alkyl group, a cyano group, -—NR 7 R 8 (where R 7 and R 8 are each independently hydrogen atom or a Ci Cs alkyl Le group), a nitro group, a force Rubamoiru group, N-(Ci Cs alkyl) Cal Pamoiru group, N, N-di (C 1 -C 5 alkyl ) Carpamoyl group, or —NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or aryl group) Which may be substituted with an aryl group,
  • R 7 and R 8 are each independently a hydrogen atom or a Ci Cg alkyl group
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Ci Cs alkyl group which may be substituted with a halogen atom, and may form a ring or a branched or ring;
  • Ci ⁇ c 5 alkoxy group May be substituted by C port disilazane atoms, and Z or optionally branched or form a ring Ci ⁇ c 5 alkoxy group
  • Ci Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are independently, a hydrogen atom or a C 1 -C 5 alkyl Le group), a nitro group, Karupamoiru group, N-(Ci Cs alkyl) Cal Pamoiru group; N, N-di (C 1 -C 5 alkyl) Karupamoiru Or an NR 7 COR 9 (wherein R 7 is a hydrogen atom or a Ci Cs alkyl group, and R 9 is an optionally branched C Cg alkyl group or an aryl group). You may have an ariel group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • An aryl group that may be substituted with at least one group selected from the group consisting of:
  • the molar ratio of the amine represented by the formula (II) and / or (II ′) used in the above reaction is not particularly limited, but is preferably 3: 1 to 1: 1: 3, more preferably 2: 1 to 1: 2, even more preferably about 1: 1.
  • the solvent (A) used in the present invention may be any solvent as long as it does not react with amine or carbon disulfide, and includes lower alcohols such as ethanol, methanol, propanol, and ptanol. It is an organic solvent. In particular, it is preferable to use ethanol because it is easy to handle in industrial production and the reaction intermediate (a 1) described later is efficiently produced.
  • the amount of the solvent (A) used is appropriately set by those skilled in the art according to the total amount of the amine used and Z or carbon disulfide used in the above formulas (II) and / or (I). Can be done.
  • the reaction of the amine represented by the above formula (II) and / or (II ′) with carbon disulfide is preferably carried out under reflux.
  • the reaction time is not particularly limited, It is preferably performed for 6 to 18 hours, more preferably for 10 to 14 hours.
  • reaction intermediate (a 1) is produced.
  • the produced reaction intermediate (a 1) may be purified by means known to those skilled in the art, if necessary.
  • reaction intermediate (a 1) obtained as described above can be represented, for example, by the following formula (VD: (VI)
  • (i) may be substituted with halogen atoms, and or may form a branched or cyclic, C 1 -C 5 alkyl group;
  • An alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each independently, a hydrogen atom or a C 1 -C 5 alkyl Le group), a nitro group, Karupamoiru group, N- (Ji-alkyl) Cal Pamoiru group, N, N-di (C 1 ⁇ C 5 'alkyl) Carpamoyl group, or one NR 7 COR 9 (where R 7 is a hydrogen atom or Ci Cs alkyl group, and R 9 is a C 1 -C 5 alkyl group or aryl group which may be branched) ) May be substituted with Ciano group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • An arolealkyl group optionally substituted with at least one group selected from the group consisting of:
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or an alkyl group having 5 to 5 alkyl groups, and R 9 is an optionally branched C 1 to C 5 alkyl group or an aryl group.
  • the compound represented by the formula (VI) has an asymmetric center at the carbon atom to which the R 3 group and the R 4 group are respectively bonded.
  • the compound represented by the formula (VI) has the following structure:
  • It preferably has a structure represented by
  • reaction intermediate (a 1) is then converted into Hg (II) salt (HgX 2 ) or 1 [3- (dimethylamino) propyl] — 3 in the solvent (B).
  • Hg (II) salt HgX 2
  • EDC I ethyl carposide hydrochloride
  • reaction intermediate (bl) is produced by reacting with the amine represented by
  • R 5 and R 6 are each independently
  • (ii) may be substituted with a halogen atom and / or may form a branch or ring
  • An alkyl group of (iii) C 2 -C 2 which may be substituted with a halogen atom and / or may form a branch or a ring.
  • Ci Cs alkyl group which may be branched, Cyan group, one NR 3 ° R 31 (wherein R 3 ° and R 31 are each independently a hydrogen atom or Ci to C 5 alkyl group), Nitro group, Carpamoyl group, N— (Ci Cs alkyl) Forced rubamoyl group, N, N—Di (C 1 -C 5 alkyl) Carpamoyl group, or one NHCOR 9 (where R 9 is branched) Which is optionally substituted with a Ci C alkyl group), an aryl group,
  • R 30 and R 31 are each independently a hydrogen atom or a Ci Cs alkyl group
  • Ci Cg alkyl group which may be branched
  • Ci Ci to C 5 alkoxy group which may be branched
  • Ci Cs alkyl group which may be branched, cyano group, one NR 3 .
  • R 31 (wherein R 3D and R 31 are each independently a hydrogen atom or a Ci C 5 alkyl group), a nitro group, a carbamoyl group, N— (C 1 -C 5 alkyl) carbamoyl group N, N—di (C 1 -C 5 alkyl) force rubamoyl group or one NR 7 COR 9 (where R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 Is an optionally branched Ci Cs alkyl group or aryl group), an aryl group,
  • R 3 ° and R 31 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or Ci Cs alkyl group, and R 9 is an optionally branched 5 alkyl group or aryl group
  • R 7 is a hydrogen atom or Ci Cs alkyl group
  • R 9 is an optionally branched 5 alkyl group or aryl group
  • a heteroalkylenole group optionally substituted with at least one group selected from the group consisting of:
  • a 5 alkoxy group optionally substituted with a halogen atom and / or optionally forming a branch or ring,
  • a 5- alkyl group, a cyano group, one NR 7 R 8 (where R 7 and R 8 are each, independently, a hydrogen atom or a C 1 -C 5 alkyl group), a nitro group, a force Rubamoiru group, N- (C 1 ⁇ C 5 alkyl Le) Karupamoiru group, N, N-di (C 1 ⁇ C 5 alkyl) force rubamoyl group, or one NR 7 COR 9 (where R 7 is a hydrogen atom or Ci Cs alkyl group, and R 9 may be branched C 1 -C 5 alkyl) Group or aryl group), an aryl group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or Ci to C 5 alkyl group, and R 9 is a C 1 to C 5 alkyl group or aryl group which may be branched
  • R 7 is a hydrogen atom or Ci to C 5 alkyl group
  • R 9 is a C 1 to C 5 alkyl group or aryl group which may be branched
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • a C 1 -C 5 alkoxy group which may be substituted with a halogen atom and which may form Z or a branched or ring;
  • a C 1 -C 5 alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each independently hydrogen atom or a C 1 -C 5 alkyl group), a nitro group, Karupamoiru group, N- (C 1 ⁇ C 5 alkyl) force / Rebamo I le group, N, N-di ( C Cs alkyl) Carpamoyl group, or one NR 7 COR 9 (where R 7 is a hydrogen atom or the same 5- alkyl group, and R 9 may be branched C 1 -C 5 An alkyl group or an aryl group), an aryl group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched C 1 -C 5 alkyl group or aryl group
  • R 7 is a hydrogen atom or a C 1 -C 5 alkyl group
  • R 9 is an optionally branched C 1 -C 5 alkyl group or aryl group
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • a group selected from the group consisting of R 5 and R 6 together are a divalent group represented by 1 (CH 2 ) m — (where m is an integer from 2 to 8).
  • amine represented by the above formula (III) include ptylamine, diptylamin, pyrrolidine, otatillamin, octadecylamine, 3, 5— (CF 3 ) 2 _C 6 H 4 —NH 2 , 3 , 5- (OCH 3 ) 2 — C 6 H 4 — NH 2 and the like, but not limited thereto.
  • the molar ratio of the reaction intermediate (a 1) used in the above reaction to the amine represented by the formula (III) is not particularly limited, but is preferably 1: 1 to 1: 5, more preferably 1: 1.2 to 1: 3, even more preferably about 1: 1.5.
  • the solvent (B) used in the present invention may be any solvent as long as it does not hinder the reaction between thiourea and amine.
  • DMF N-dimethylformamide
  • DMA Organic solvents including aprotic solvents
  • it is preferable to use DMF because it is easy to handle in industrial production and the reaction intermediate (bl) described later is efficiently produced.
  • the amount of the solvent (B) used can be appropriately set by those skilled in the art depending on the amount of the reaction intermediate (a 1) used and the total amount of the amines represented by Z or formula (III). .
  • Hg (II) salt (HgX 2 ) used in the present invention is mercury (II) chloride.
  • the amount of Hg (II) salt used in the above reaction is set, for example, based on the amount of the above reaction intermediate (a 1) used.
  • the molar ratio of the reaction intermediate (a 1) and the Hg (II) salt to be used is not particularly limited, but is preferably 1: 1 to 1: 5, more preferably 1: 1.2 to 1: 3, even more preferably about 1: 1.5.
  • Hg (II) salt HgX 2
  • 1- [3- (dimethylamino) pill] —3-ethyl carbodiimide hydrochloride (EDC I) is used instead of or together with the above Hg (II) salt (HgX 2 ).
  • EDC I 3-ethyl carbodiimide hydrochloride
  • the reaction between the reaction intermediate (a 1) and the amine represented by the formula (III) is preferably performed at a temperature of 60 ° C to 100 ° C, more preferably 70 ° C to 90 ° C. It is.
  • the reaction time is not particularly limited, but is preferably 6 hours to 18 hours, more preferably 10 hours to 14 hours.
  • reaction intermediate (b l) is produced.
  • the produced reaction intermediate (bl) may be purified by means known to those skilled in the art, if necessary.
  • the reaction intermediate (bl) is a kind of guanidine monothiourea compound having protecting groups (Y and / or Y ′) at both ends.
  • the guanidine monothiourea compound represented by the above formula (I) can be produced using the reaction intermediate (bl).
  • R 1 and R 2 are each independently an aryl group, wherein the aryl group is
  • a 5- alkoxy group which may be substituted with a halogen atom and / or may form a branch or a ring,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or a 0 to 0 5 alkyl group, and R 9 may be branched; a 5 to 5 alkyl group or an aryl group), and
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • reaction intermediate (b 1) is deprotected by a method well known to those skilled in the art.
  • the isothiocyanate represented by the formula (IV) or (IV ′) is not particularly limited, but specific examples thereof include 3,5-bis (trifluoromethyl). Examples include phenyl isothiocyanate, 1-naphthyl isothiocyanate, 3,5-dichlorophenyl isothiocyanate, 3-methoxyphenyl isothiocyanate, and the like. It is particularly preferred to use 3,5-bis (trifluoromethyl) phenylene sothiocyanate.
  • the molar ratio of the protected reaction intermediate (bl) to the isothiocyanate represented by the formula (IV) and / or (IV ') is not particularly limited.
  • the equivalent ratio of the amino group and the isothiocyanate group is preferably 1: 1 to 1: 5, and more preferably 1: 1.2 to 1: 2.
  • any type of solvent can be used as long as it does not interfere with the reaction between amine and isothiocyanate.
  • an organic solvent such as tetrahydrofuran should be used appropriately. Is preferred.
  • the reaction of the deprotected reaction intermediate (bl) with the isothiocyanate represented by the formula (IV) and ino or (IV,) is preferably 60 ° C to 100 ° C, More preferably, it is carried out at a temperature of 70 ° C to 90 ° C.
  • the reaction time is not particularly limited, but it is preferably 12 to 22 hours, more preferably 15 to 18 hours.
  • the guanidine monothiorea compound of the present invention represented by the formula (I) is produced.
  • the obtained guanidine monothiorea compound of the formula (I) may be purified by means known to those skilled in the art, if necessary.
  • Reaction intermediate (a 2) is produced by reacting with the isothiocyanate represented by
  • the amine of I,) is the same as that which can be used in the first method.
  • R 11 is an aryl group, and the aryl group is
  • C port Gen atoms May be substituted by C port Gen atoms, and / or optionally branched or form a cyclic C 1 -C 5 alkyl group,
  • a 5- alkoxy group which may be substituted with a halogen atom and / or may form a branch or a ring,
  • R 7 and R 8 are each independently a hydrogen atom or a Ci Cg alkyl group
  • R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or aryl group
  • R 7 is a hydrogen atom or a 5 alkyl group
  • R 9 is an optionally branched Ci Cs alkyl group or aryl group
  • the isothiocyanate represented by the formula (V) is not particularly limited, but specific examples thereof include 3,5-bis (trifluoromethyl) phenyl isothiocyanate, 1-naphthyl isothiocyan 3, 5-dichlorodiphenyl thiothiocyanate, 3-methoxyphenyl isothiocyanate, etc. It is particularly preferable to use 3,5-bis (trifluoromethyl) phenyl isothiocyanate. .
  • the molar ratio of the amine represented by the formula (II) and Z or ( ⁇ ⁇ ,) to the isothiocyanate represented by the formula (V) is not particularly limited.
  • the equivalent ratio with the isothiocyanate group is preferably 1: 1 to 1: 5, more preferably 1: 1.2 to 1: 2.
  • any type of solvent can be used as long as it does not interfere with the reaction between amine and isothiocyanate.
  • an organic solvent such as tetrahydrofuran is preferably used as appropriate. .
  • the solvent (C) used in the present invention is an organic solvent such as tetrahydrofuran, acetonitrile, or toluene.
  • tetrahydrofuran is preferably used because it is easy to handle in industrial production and the reaction intermediate (a 2) described later is efficiently produced.
  • the amount of the solvent (C) used is the amount of the amine represented by the above formula (II) and / or (I) and / or the isothiocyanate represented by the formula (V). Depending on the total amount used, it can be appropriately set by those skilled in the art.
  • reaction of the amine represented by the above formula (I I) and / or (11,) with the isothiocyanate represented by the formula (V) is performed, for example, at an ice temperature to room temperature.
  • the reaction time is not particularly limited, but is preferably 18 hours to 25 hours, more preferably 19 hours to 22 hours.
  • reaction intermediate (a 2) is produced.
  • the produced reaction intermediate (a 2) may be purified by means known to those skilled in the art, if necessary.
  • the reaction intermediate (a 2) obtained as described above can be represented, for example, by the following formula (VI).
  • (i) may be substituted with a halogen atom, and Roh or may form a branched or cyclic, c 1 to c 5 alkyl groups;
  • an aralkyl group wherein the aryl moiety constituting the aralkyl group may be substituted with a halogen atom, and or a c 1 to c 5 alkyl group which may form a branch or a ring,
  • a C Cg alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are Independently, a hydrogen atom or Ci Cs alkyl group), an etro group, a strong rubamoyl group, an N— (C 1 -C 5 alkyl) carbamoyl group, an N, N—di (Ci Cs alkyl) force rubamoyl group Or one N R 7 COR 9 (where, R 7 is a hydrogen atom or Ji ⁇ Ji 5 alkyl group, and R 9 is Ru branched may be.
  • ⁇ Ji 5 alkyl or Ariru group Der substituted with May have been, allyl group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Ci Cs alkyl group which may be substituted with a halogen atom and / or may form a branch or a ring,
  • C port Gen atoms May be substituted by C port Gen atoms, and / or optionally branched or form a cyclic C 1 -C 5 alkoxy group,
  • a C Cs alkyl group, a cyano group, one NR 7 R 8 (wherein R 7 and R 8 are each independently substituted with a halogen atom and / or optionally branched or ring-formed) independently, a hydrogen atom or a C 1 -C 5 alkyl Le group), a nitro group, a force Rubamoiru group, N- (C 1 ⁇ C 5 alkyl) Cal Bamoiru group; N, N-di (C 1 -C 5 alkyl) Carpamoyl group, or 1 N R 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched C Cs alkyl group or an aryl group).
  • R 7 and R 8 are each independently substituted with a halogen atom and / or optionally branched or ring-formed
  • R 7 and R 8 are each independently substituted with a halogen atom and /
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C Cs alkyl group, and R 9 is an optionally branched Ci C 5 alkyl group or an aryl group), and Halogen atom
  • R 11 is an aryl group, and the aryl group is.
  • Ci Cs alkyl group which may be substituted with a halogen atom, and / or may form a branch or a ring,
  • R 7 and R 8 Each independently represents a hydrogen atom or a C Cs alkyl group), a nitro group, a force rubermoyl group, N— (C Cs alkyl) a force ruber moyl group, N, N—di (C 1 -C S alkyl) Force ruby moyl group Or one substituted with NR 7 COR 9 (wherein R 7 is a hydrogen atom or the same 5- alkyl group, and R 9 is an optionally branched 5- alkyl group or aryl group). You may have an ariel group,
  • R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group
  • R 7 is a hydrogen atom or a 5 alkyl group, and R 9 is an optionally branched C Cs alkyl group or an aryl group), and
  • the compound represented by the formula (VI ⁇ ) has an asymmetric center at the carbon atom to which the R 3 group is bonded. Accordingly, the compound represented by the formula (VII) has the following structure:
  • reaction intermediate represented by the above formula (VII) is used as an intermediate for producing a catalyst for producing an etroalcohol compound (for example, a two-phase phase transfer catalyst) as described later. If you get From the point that optical purity and yield of nitro alcohol compound are excellent, the formula
  • reaction intermediate (a 2) is then converted into at least one selected from the group consisting of the formulas (II) and (II ′) in the medium (D).
  • the reaction intermediate (b 2) is formed by reacting with the amine. Reaction intermediate (a 2) used in the above reaction with formula (I I) and Z or
  • the molar ratio with the amine represented by ( ⁇ ⁇ ') is not particularly limited, but is preferably 1: 1 to 1: 5, more preferably 1: 1, 2 to 1: 3, and even more preferable. Is about 1: 1.5.
  • the solvent (D) used in the present invention is an organic solvent such as N, N dimethylformamide (DMF) or N, N dimethylacetamide (DMA).
  • DMF N, N dimethylformamide
  • DMA N, N dimethylacetamide
  • the amount of the solvent (D) used depends on the amount of the above reaction intermediate (a 2) and the total amount of the amine used represented by Z or the formula (II) (or the formula (II ')). It can be set appropriately by those skilled in the art.
  • reaction of the reaction intermediate (a 2) with the amine represented by the formula (II) and Z or (11,) is preferably carried out at a temperature of 0 ° C to 40 ° C.
  • the reaction time is not particularly limited, but it is preferably performed over 3 hours to 24 hours. In this way, reaction intermediate (b 2) is produced.
  • Generated reaction intermediate (b 2) may be purified by means known to those skilled in the art, if necessary.
  • the reaction intermediate (b 2) is a kind of guanidine monothiourea compound having protecting groups (Y and Z or Y ′) at both ends.
  • the guanidine monothiourea compound represented by the above formula (I) can be produced using the reaction intermediate (b 2).
  • Reaction intermediate (b 2) Reaction intermediate
  • the guanidine monothiourea compound represented by the formula (I) of the present invention can be efficiently produced using a simpler process.
  • Ararukiru a group may Ariru portions constituting the optionally substituted with C port Gen atoms, and / or branched or rings formed by C 1 optionally -C 5 alkyl group ,
  • C port Gen atoms May be substituted by C port Gen atoms, and / or optionally branched or form a cyclic C 1 -C 5 alkoxy group,
  • a C 1 -C 5 alkyl group, a cyano group, one NR 7 R 8 (where R 7 and R 8 Each independently represents a hydrogen atom or a Ci Cs alkyl group), a nitro group, a strong rubamoyl group, an N— (C 1 to C 5 alkyl) carbamoyl group, an N, N—di (C 1 to C 5 alkyl) a strong rubermoyl group, or one NR 7 COR 9 (where R 7 is a hydrogen atom or a 5- alkyl group, and R 9 may be branched C Cs alkyl group or aryl group) An aryl group, which may be substituted with
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group),
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or a C 1 -C 5 alkyl group, and R 9 is an optionally branched Ci Cs alkyl group or aryl group), and Halogen atom
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • a C i to C 5 alkyl group which may be substituted with a halogen atom and which may form Z or a branched or ring;
  • Ci to C 5 alkoxy group that may be substituted with a halogen atom and that may form Z or a branched or ring;
  • a C 1 -C 5 alkyl group, a cyano group, one NR 7 R 8 (where R 7 and R 8 Each independently represents a hydrogen atom or a Ci Cs alkyl group), a nitro group, a strong rubamoyl group, an N— (C 1 -C 5 alkyl) carbamoyl group; N, N—di (C 1 -C 5 alkyl) carbamoyl group, or — NR 7 COR 9 (wherein R 7 is a hydrogen atom or a Ci Cs alkyl group, and R 9 may be branched Ci to C 5 alkyl group or aryl group) An aryl group, which may be substituted with
  • NR 7 R 8 (wherein R 7 and R 8 are each independently a hydrogen atom or a C 1 -C 5 alkyl group),
  • NR 7 COR 9 (wherein R 7 is a hydrogen atom or a Ci Cg alkyl group, and R 9 is a C 1 to C 5 alkyl group or an aryl group which may be branched), and Neurogen atom
  • An aryl group which may be substituted with at least one group selected from the group consisting of: and a nitroalkane which may be substituted with a hydroxyl group.
  • the aldehyde represented by the formula (VIII) is not particularly limited, and examples thereof include cyclohexanecarboxaldehyde, cyclopentanecarboxyaldehyde, tert_butyraldehyde, isopropylaldehyde, 2-pentylaldehyde, 3- Phenylpropionaldehyde, benzaldehyde, 2-naphthaldehyde, phenylacetaldehyde, p-tolualdehyde, p-fluorobenzaldehyde, p-methoxybenzaldehyde, acetoaldehyde, propioaldehyde And pentanal.
  • the nitroalkane which may be substituted with a hydroxyl group is not particularly limited, and examples thereof include nitromethane, nitroethane, 1-12 tropane, 2-nitropropane, 1-12 tropbutane, 2-nitrotropane, 2 —Nito Oral ethanol.
  • the amount of the nitroalkane optionally substituted with the hydroxyl group is preferably based on the amount of the aldehyde represented by the formula (VIII). Is 1 equivalent to 10 equivalents, more preferably 2 equivalents to 5 equivalents. If the amount of the -troalkane used is less than 1, the target nitroalcohol compound may not be produced sufficiently. In addition, even if the amount of the utroalkane used exceeds 10 equivalents, the yield of the resulting nitroalcohol compound is not changed, and the production may be inferior.
  • a guanidine monothiourea compound represented by () or (1 ") is preferred. Alternatively, it functions as a phase transfer catalyst in an appropriate medium and in the presence of an inorganic base.
  • Formula () or () guanidine one Chiourea compound represented by the relative aldehyde to 1 mole of the formula (VIII), preferably 1 molar 0 / 0-2 0 mol 0/0, more Preferably 5 mol 0 /. ⁇ 1 5 mole 0/0, may be further used in a more preferred ratio of 8 mol% 1 2 mol% properly.
  • Examples of the medium used in the above Henry reaction include toluene, benzene, xylene, dichloromethane, black mouth honolem, hexane, decane, ethinoreethenole, tetrahydrofuran, isopropyl ether, dioxane, and other organic solvents, and water. .
  • the medium may be a two-phase medium of these organic solvents and water (for example, the volume ratio is 7: 1 to 1: 7, preferably 5: 1 to 1: 5).
  • the medium may be used in an amount (ml) / weight (g) ratio of 3 to 30 times, more preferably 8 to 25 times the aldehyde of the formula (V I I I).
  • the inorganic base used in the Henry reaction examples include potassium hydroxide, lithium hydroxide, sodium hydroxide, power hydroxide, calcium hydroxide, rubidium hydroxide, hydroxide such as cesium hydroxide, and the like. Combinations are listed.
  • the inorganic base is preferably 10 mole 0 / to the aldehyde of formula (VIII). It can be used to 2 0 0 mole 0/0.
  • the inorganic base may be used in the form of an aqueous inorganic base solution.
  • the Henry reaction is also preferably carried out at a suitable temperature between 130 ° C. and room temperature, more preferably between 120 ° C. and 0 ° C. While this reaction continues, the reaction can be carried out with stirring for an appropriate time until the reaction proceeds sufficiently.
  • the reaction time is preferably 30 minutes to 70 hours, more preferably 1 hour to 24 hours.
  • halides of alkali metals such as KB F 4 , NaBF 4 , KB r, Na Br, Li I, Na l, KI, etc. as additional additives in the reaction system, or You may add a combination of them.
  • the additive is preferably against an aldehyde of formula (VIII) may use 10 molar 0/0 100 mol 0/0.
  • flash chromatography was performed using silica gel 60 (spherical, particle size 0.040 mm to 0.100 mm; manufactured by Kanto Chemical Co., Inc.).
  • Optical rotation was measured with a JASCO DIP polarimeter 370 (manufactured by JASCO Corporation).
  • the IR spectrum was measured with a JASCO VALOR-IIIFT—IR spectrophotometer.
  • the NMR spectrum and 13 C NM R spectrum were measured with a J EOL ALPHA500 apparatus (manufactured by JEOL Ltd.).
  • the mass spectrum was measured with a J EOL JMA—HX 110 spectrometer (manufactured by JEOL Ltd.).
  • Bn represents a benzyl group
  • methanesulfonyl chloride (3.4 mL, 44.4 mm o 1) was added dropwise to a solution of the alcohol, triethylamine (8.3 mL, 59.2 mm o 1) in dichloromethane (10 OmL) at 0 ° C. And stirred for 1 hour. Saturated aqueous sodium hydrogen carbonate solution was added, and the organic layer was extracted with dichloromethane and concentrated under reduced pressure. The obtained residue was dissolved in DMF (7 OmL), sodium azide (9.62 g, 148 mmo 1) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hours.
  • L-Fulanin (3.0 g, 33. 7m Amin (6-2) was obtained in the same manner as in Example 1 except that mo 1) was used.
  • thiourea (7-2) was obtained in the same manner as in Example 1 except that amide (6-2) (749 mg, 4.3 mmo 1) was used instead of amide (6).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne : un composé guanidine-thio-urée utile pour la fabrication par réaction de Henry d'un alcool nitro désiré présentant une grande pureté optique, un rendement élevé et un impact sur l'environnement réduit ; ainsi qu'un procédé de fabrication d'un alcool nitro utilisant ce composé. Le composé guanidine-thio-urée peut être obtenu par des étapes relativement simples, et permet de fabriquer un alcool nitro désiré présentant une grande pureté optique et un rendement élevé.
PCT/JP2006/315364 2005-07-29 2006-07-27 Compose guanidine-thio-uree et procede de fabrication d'un alcool nitro utilisant ce compose Ceased WO2007013681A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2007526948A JP4775915B2 (ja) 2005-07-29 2006-07-27 グアニジン−チオウレア化合物およびそれを用いたニトロアルコールの製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005-222279 2005-07-29
JP2005222279 2005-07-29

Publications (1)

Publication Number Publication Date
WO2007013681A1 true WO2007013681A1 (fr) 2007-02-01

Family

ID=37683553

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/315364 Ceased WO2007013681A1 (fr) 2005-07-29 2006-07-27 Compose guanidine-thio-uree et procede de fabrication d'un alcool nitro utilisant ce compose

Country Status (2)

Country Link
JP (1) JP4775915B2 (fr)
WO (1) WO2007013681A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010523523A (ja) * 2007-04-03 2010-07-15 ノバルティス アーゲー 新規方法
CN102274736A (zh) * 2011-06-28 2011-12-14 苏州大学 三氯化铝在催化胺与碳化二亚胺加成反应中的应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998024753A1 (fr) * 1996-12-02 1998-06-11 Chisso Corporation Derives de nitro-alcool actifs optiquement, derives d'amino-alcool actifs optiquement et leur procede de preparation
WO2002041984A2 (fr) * 2000-11-01 2002-05-30 The Board Of Trustees Of The Leland Stanford Junior University Compositions catalytiques et procedes pour des reactions aldol asymetriques

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4593289B2 (ja) * 2003-02-27 2010-12-08 長瀬産業株式会社 四級アンモニウムビフルオリド化合物およびそれを用いたニトロアルコールの製造方法
US7790900B2 (en) * 2003-05-23 2010-09-07 Sumitomo Chemical Company, Limited Method for producing an optically active nitro compound
WO2005000803A2 (fr) * 2003-06-30 2005-01-06 Sumitomo Chemical Co Compose d'uree asymetrique et procede pour produire un compose asymetrique par reaction d'addition de conjugue asymetrique avec ledit compose comme catalyseur
JP4357332B2 (ja) * 2004-03-24 2009-11-04 三井化学株式会社 光学活性ニトロアルコール類の製造法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998024753A1 (fr) * 1996-12-02 1998-06-11 Chisso Corporation Derives de nitro-alcool actifs optiquement, derives d'amino-alcool actifs optiquement et leur procede de preparation
WO2002041984A2 (fr) * 2000-11-01 2002-05-30 The Board Of Trustees Of The Leland Stanford Junior University Compositions catalytiques et procedes pour des reactions aldol asymetriques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SOHTOME Y. ET AL.: "Diastereoselective Henry reaction catalyzed by guanidine-thiourea bifunctional organocatalyst", SYNLETT, no. 1, 2006, pages 144 - 146, XP003007763 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010523523A (ja) * 2007-04-03 2010-07-15 ノバルティス アーゲー 新規方法
CN102274736A (zh) * 2011-06-28 2011-12-14 苏州大学 三氯化铝在催化胺与碳化二亚胺加成反应中的应用

Also Published As

Publication number Publication date
JP4775915B2 (ja) 2011-09-21
JPWO2007013681A1 (ja) 2009-02-12

Similar Documents

Publication Publication Date Title
CN107382783B (zh) 一种手性β-氨基酸衍生物及其制备方法
JP3504254B2 (ja) 光学活性アミノアルコールおよびその中間体の製造方法
Nordstrøm et al. Iridium catalysed synthesis of piperazines from diols
WO2008038578A1 (fr) sel d'ammonium quaternaire optiquement actif prÉsentant une asymÉtrie axiale et procÉdÉ de production d'acideS α-aminÉs et de dÉrivÉs de ceux-ci au moyen dudit sel
WO2007013681A1 (fr) Compose guanidine-thio-uree et procede de fabrication d'un alcool nitro utilisant ce compose
Muthusamy et al. Rhodium (II) catalyzed synthesis of macrocycles incorporating oxindole via O–H/N–H insertion reactions
JP2010030992A (ja) 光学活性アミン化合物の製造方法
ES2227264T3 (es) Accesorios quirales de 4-ciclohexil-1,3,2-oxazaborolidina.
JP4357332B2 (ja) 光学活性ニトロアルコール類の製造法
KR100718166B1 (ko) 구리 촉매하의 삼성분 짝지움 반응에 의한ｎ-술포닐아미딘의 제조방법
JP5408662B2 (ja) ジスルホン酸化合物の製法、不斉マンニッヒ触媒、β−アミノカルボニル誘導体の製法及び新規なジスルホン酸塩
JP4427266B2 (ja) β−アラニン誘導体およびその製造方法
CN112479968A (zh) 一种催化氢胺化反应制备2-甲基吡咯烷化合物的合成方法
JP5344523B2 (ja) 立体選択的にストレッカー反応を進行させ得る触媒、およびそれを用いたα−アミノニトリル誘導体を立体選択的に製造するための方法
JP4802191B2 (ja) 軸不斉を有する光学活性な４級アンモニウム塩およびそれを用いたα−アミノ酸およびその誘導体の製造方法
KR101630204B1 (ko) 키랄 베타 히드록시 카보닐 화합물의 제조 방법 및 이에 의해 제조된 베타 히드록시 카보닐 화합물
KR101446708B1 (ko) 광학활성 에틸렌디아민 유도체 및 이의 제조방법
CN110981808B (zh) 银与碱协同催化合成非对映2-咪唑啉酮类化合物的方法
CN113461690B (zh) 一种手性4,6-二氧八氢吡咯并[3,4-c]吡咯-1-羧酸酯类化合物的合成方法
JP3958101B2 (ja) 固定化された酸化反応用試薬
CN106478721B (zh) 一种樟脑衍生的恶唑啉‑氧磷有机小分子催化剂及其制备方法
Xu Regioselective tungsten-catalyzed decarboxylative amination of allylic alcohols with isocyanates
JP4595178B2 (ja) アミン化合物、中間体、製造法および光学分割剤
JPWO2002076958A1 (ja) ５−置換オキサゾール化合物および５−置換イミダゾール化合物の製造方法
CA2556962A1 (fr) Aminoalkylnaphtols chiraux tertiaires

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2007526948

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06782224

Country of ref document: EP

Kind code of ref document: A1