Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
  • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
  • C07D213/46—Oxygen atoms
  • C07D213/48—Aldehydo radicals

Definitions

• the invention relates to a process for the preparation of 5-arylnicotinaldehydes by reduction of the corresponding 5-arylnicotinic acids by means of catalytic hydrogenation with a palladium complex stabilized by a phosphine in the presence of di-tert-butyl dicarbonate, the molar ratio of palladium complex to 5 - Arylnicotinic acid between 1: 500 to 1: 8000 and the molar ratio of 5-arylnicotinic acid to di-tert-butyldicarbonate is between 1: 1 and 1: 5.
• 5-Arylnicotinaldehydes are important intermediate or end products in industrial organic chemistry. Correspondingly substituted derivatives are particularly valuable intermediates for the synthesis of highly refined end products or are themselves such end products, in particular for crop protection, such as Fungicides, insecticides, herbicides or pesticides or for the production of pharmaceutically highly effective substances.
• a production of the corresponding 5-arylnicotinaldehydes on an industrial scale requires the most economical and environmentally compatible representation possible.
• WO 01/58873 (Merck Patent GmbH) describes a process for the preparation of 5-arylnicotinaldehydes by reducing the corresponding 5-arylnicotinaldehydes by means of catalytic hydrogenation in the presence of pivalic anhydride, in which a palladium Complex is used, the molar ratio of palladium to ligand being 1 to 5 to 1 to 15 for monodentate ligands and 1 to 2.5 to 1 to 7.5 for bidentate ligands.
• EP 1108706 (Japan Science and Technology Corp.) describes a
• the object on which the invention is based was to find a process for the preparation of 5-arylnicotinaldehydes which is also suitable for these
• Substance class enables a cheaper and more environmentally friendly production without having the disadvantages mentioned above.
• 5-arylnicotinaldehydes can be obtained by reducing the corresponding 5-arylnicotinic acids by means of catalytic hydrogenation with a palladium complex stabilized by a phosphine in the presence of di-tert-butyl dicarbonate, the molar ratio of palladium complex being increased 5- arylnicotinic acid between 1: 500 to 1: 8000 and the molar ratio of 5-arylnicotinic acid to di-tert-butyldicarbonate is between 1: 1 and 1: 5.
• a molar ratio of 5-arylnicotinic acid to di-tert-butyl dicarbonate between 1: 1 and 1: 2 is particularly preferred, and a ratio of 1: 1.5 is most preferred.
• a molar ratio of palladium complex to 5-arylnicotinic acid between 1: 3000 and 1: 5000.
• the process according to the invention enables the amount of palladium used to be reduced to below 0.025 mol%, based on the amount of carboxylic acid.
• the use of di-tert-butyl dicarbonate enables higher yields of 5-arylnicotinaldehyde with lower amounts of catalyst than would have been expected according to the prior art (see EP 1108706).
• the preferred object of the invention is in particular a process for the preparation of 5-arylnicotinaldehydes of the formula I.
• A is an unsubstituted or mono- or polysubstituted by R, F, Cl, -CN, -NO 2 , -CF 3 , -OCF 3 , -OCHF2, -OCF2CF3 -OCHFCF3 or Oalkyl substituted phenyl radical or naphthyl radical, in which also one or several CH groups can be replaced by N, and
• An aldehyde of the formula I is preferred, in which A denotes a 4-fluorophenyl group.
• the 5-arylnicotinic acids used as starting materials for the process according to the invention are either known or are prepared by methods known per se, as described in the literature (for example in standard works such as Houben-Weyl, Methods of Organic Chemistry, Georg-Thieme-Verlag, Stuttgart) and under reaction conditions that are known and suitable for the reactions mentioned. However, use can also be made of variants which are known per se and are not mentioned here in detail.
• the 5-aryl nicotinic acids are preferably prepared by Suzuki coupling (N. Miyaura, A. Suzuki, Chem. Rev. 95, 2457 (1995)) by using 5-bromo-nicotinic acid, 5-bromo-nicotinic acid alkyl ester, 5-bromo nicotine alcohol or its alkyl carboxylic acid ester with the corresponding arylboronic acids under known reaction conditions to give the compounds of the formulas II, III or IV or V:
• R 3 is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl,
• esters of the formulas III and V are then hydrolyzed by customary processes to obtain the free acid of the formula II or the alcohol of the formula IV and the alcohol of the formula IV is oxidized to the acid formula II by customary methods.
• Table 1 shows the stabilizing effect of a large excess of triphenylphosphine (PPhs) on the catalyst, which increases the conversion of acid. It also becomes clear that good conversion rates with small amounts of palladium catalyst are only possible with di-tert-butyl dicarbonate as the activating reagent. When the expensive pivalic anhydride is used as the activating reagent, the large excess of phosphine required to stabilize the catalyst leads to an increased formation of the undesired by-product 3- (4-fluorophenyl) pyridine by decarboxylation.
• Phs triphenylphosphine
• Tab 1 Conditions- 50 mmol 5- (4-fluoropenyl) -n ⁇ cot ⁇ nsaure; 0 05 mmol Pd (OAc) 2 , PPh 3 100 ml THF, 100 ° C, 100 bar H 2 ; 20 h 1) 75 mmol of 5- (4-fluorophenyl) nicotinic acid, 0 019 mmol of Pd (OAc) 2 ; 150 ml THF; 100 ° C, 100 bar H 2 ; 24
• a molar ratio of palladium complex to phosphine of between 1:20 and 1: 100 is preferred, this ratio having to be related to the carboxylic acid concentration, since a larger carboxylic acid: Pd ratio also requires a larger excess of phosphine. As can be seen from the table, an 8-fold excess of phosphine is sufficient for 0.1 mol% Pd (only applies to di-tert-butyl dicarbonate). A molar ratio of palladium complex to phosphine between 1:25 and 1:50 is particularly preferred.
• Metal complexes of palladium stabilized by phosphines are suitable as catalysts for achieving high conversions in the hydrogenation of nicotinic acids. Platinum complexes are also conceivable.
• the catalytically active complexes are obtained in situ from metal precursor complexes with corresponding phosphines or directly through defined metal-phosphine complexes.
• COD 1,5-cyclooctadiene
• L phosphorus ligand Pd (OAc) 2 is particularly preferred.
• Suitable phosphines can be:
• Triphenylphosphine and diphenyl (2-methoxyphenyl) phosphine are preferred, since these two phosphine derivatives lead to products with over 91% aldehyde or the proportion in the by-product 3- (4-fluorophenyl) pyridine (in the case of 5- (4th Fluorophenyl) nicotinic acid as starting material and palladium acetate as Pd catalyst) is below 5.5%.
• Triphenylphosphine is particularly preferred.
• Suitable solvents are e.g. Hydrocarbons such as benzene, toluene or xylene; chlorinated hydrocarbons such as trichlorethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; Glycol ethers such as ethylene glycol monomethyl or monoethyl ether
• reaction time of the hydrogenation depends on the one used
• reaction temperature between 50 and 150 ° C, preferably between
• the hydrogenation is carried out at 1-200 bar of hydrogen, preferably at 80 to 120 bar.
• the reactions are preferably carried out under oxygen-free reaction conditions.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Pyridine Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=34967791

Family Applications (1)

Country Status (3)

Cited By (1)

Citations (2)

• 2004
  • 2004-06-15 DE DE200410028561 patent/DE102004028561A1/de not_active Withdrawn
• 2005
  • 2005-05-18 WO PCT/EP2005/005397 patent/WO2005123682A1/de active Application Filing
  • 2005-06-15 AR ARP050102443A patent/AR049397A1/es unknown

Patent Citations (2)

Also Published As

Similar Documents

Legal Events