Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
  • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
  • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
  • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
  • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
  • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
  • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Definitions

• the present invention relates to an improved process for the preparation of carbonyldumidazoles from imidazoles and phosgene while avoiding the coupled product irnidazole hydrochloride.
• Carbonyldiimidazole is a frequently used reagent for the introduction of carbonyl groups, for example for the production of carbonates, ureas or urethanes or for the activation of unreactive reactants in ester or amide synthesis (Angew. Chem. 74 (1962), 407).
• CDI The more elegant way to make CDI is that originally developed by Staab et al. direct phosgenation of imidazole (Liebigs Ann. Chem. 609 (1957), 75; Chem. Ber. 96 (1963), 3374; Org. Synth. Coll. Vol V (1973), 201). Although two moles of In idazole hydrochloride per mole of CDI are formed as a by-product, the first can be converted back to imidazole by basic work-up and returned to the phosgenation:
• EP-A-0 692 476 describes that described in the previous references Synthesis route only extended by a method for dewatering the solvent. However, the original regulations remain very difficult. The imidazole hydrochloride formed as a by-product must be separated from the CDI-containing reaction solution at high temperatures (80 to 100 ° C.) by filtration with exclusion of moisture. To maintain a sufficiently high product quality, a high level of technical effort must be made since the CDI is extremely sensitive to hydrolysis.
• a disadvantage of all previous processes for the direct phosgenation of imidazole is the formation of the coproduct imidazole hydrochloride, which has to be recycled in an additional process step and by which the space-time yield is halved.
• the older, unpublished WO 98/31672 relates to a process for the production of e.g. CDI by implementing e.g. Imidazole with phosgene in the presence of an organic base, e.g. Tri (n-butyl) amine.
• an organic base e.g. Tri (n-butyl) amine.
• the object of the present invention is to provide a process for the preparation of carbonyldumidazoles from imidazoles and phosgene which avoids the disadvantages mentioned.
• R is hydrogen or a C 4 alkyl radical and R is hydrogen or
• Methyl radical is by reacting at least one imidazole of the general formulas Ha and ü
• the formation of imidazole hydrochloride is avoided by adding an organic base, so that the imidazole used can be completely converted to the carbonyldiimidazole.
• the hydrochloric acid which is inevitably obtained as a by-product is bound by a stronger base than imidazole, so that the entire imidazole used can react to form carbonyldiimidazole.
• the hydrochloride of the auxiliary base then only has to be separated from the product and, after being converted into the free base, returned to the synthesis.
• Imidazole is itself a weak base (pKb value about 7) and serves as both reagent and acid scavenger in the phosgenation reaction.
• a stronger nitrogen base for example a tertiary aliphatic amine, in particular tributylamine, during the synthesis either the stronger base is preferably protonated or imidazole is re-formed from the hydrochloride formed:
• the imidazole which is thereby again present as a free base can be further phosgenated.
• an equivalent amount of tertiary nitrogen base is required according to the following gross equation.
• the advantage of the process is, inter alia, that the space-time yield is twice as high as that of the processes described hitherto, since the imidazole used is completely converted and not half of the imidazole has to be recycled as hydrochloride unused.
• the reaction is carried out in an inert solvent, preferably at a temperature in the range from 60 to 100 ° C., particularly preferably at 60 to 80 ° C. in a substituted aromatic hydrocarbon.
• Xylene or chlorobenzene is preferably used, where xylene can be present as a mixture of o-, m- and p-xylene or as one of the isomers. Xylene or its isomer mixtures are particularly preferably used.
• any base with a pKb value lower than the pKb value of imidazole is suitable as the tertiary nitrogen base.
• a tertiary amine of the general formula NR 3 is preferably used as the nitrogen base, where R in each case independently of one another is branched or unbranched Ci-io-alkyl radicals or two of the radicals with a nitrogen atom form a 5- or 6-membered heterocycloaliphatic or heteroaromatic ring which additionally can be interrupted by one or two oxygen or nitrogen atoms.
• the nitrogen base is preferably a tertiary aliphatic amine in which the radicals R are identical and are C -alkyl radicals, such as trimethyl, triethyl, tripropyl,
• Tri-n-butylarnine examples of amines in which two of the residues form a ring are N-alkylpyrrolidines and N-alkylpiperidines. Examples of rings interrupted by heteroatoms are given in N-alkylmorpholines and NjNOialkylpiperazinen.
• the amine hydrochloride formed should precipitate out of the reaction mixture as a solid phase.
• the reaction solution remains homogeneous at higher temperatures (50 to 60 ° C). Only when it cools does carbonyldiimidazole precipitate out of the reaction mixture in colorless needles, while the tributylamine hydrochloride remains completely in the solvent.
• the CDI is apparently pushed out of solution by the amine hydrochloride due to a salting-out effect, while the tributylamine hydrochloride remains dissolved in the solvent due to its longer and polar alkyl radicals.
• the CDI formed can be crystallized out by cooling the reaction mixture and separated off as a solid, the hydrochloride formed being the
• the failed CDI can be removed simply by suction under inert gas or by separation using a
• Solvent-dissolved hydrochloride of the tertiary amine can be neutralized with a stronger aqueous inorganic base, preferably an aqueous one
• Solvent can then be separated from the aqueous phase and returned to the
• a total of 51 g (0.5 mol) of phosgene are gasified at 72 to 83 ° C. within 30 minutes. After phosgene has been added, stirring is continued at 65 ° C. for 60 minutes. Working up is carried out as in Example 1. After drying, 57 g of CDI with a melting point of 112 ° C. are obtained.

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• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Steroid Compounds (AREA)

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• 1998
  • 1998-07-08 DE DE19830556A patent/DE19830556A1/de not_active Withdrawn
• 1999
  • 1999-07-06 HU HU0102739A patent/HUP0102739A3/hu unknown
  • 1999-07-06 AU AU54098/99A patent/AU5409899A/en not_active Abandoned
  • 1999-07-06 EP EP99939989A patent/EP1095024B1/de not_active Expired - Lifetime
  • 1999-07-06 US US09/720,913 patent/US6353115B1/en not_active Expired - Fee Related
  • 1999-07-06 JP JP2000559094A patent/JP2002520318A/ja active Pending
  • 1999-07-06 CN CNB998083860A patent/CN1214012C/zh not_active Expired - Fee Related
  • 1999-07-06 DE DE59907811T patent/DE59907811D1/de not_active Expired - Fee Related
  • 1999-07-06 KR KR1020017000204A patent/KR20010071762A/ko not_active Withdrawn
  • 1999-07-06 CA CA002336657A patent/CA2336657C/en not_active Expired - Fee Related
  • 1999-07-06 WO PCT/EP1999/004729 patent/WO2000002863A1/de not_active Ceased

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