EP4107143A1 - Voie efficace et sélective pour la synthèse de 2-benzoylbenzoate d'alkyle - Google Patents

Voie efficace et sélective pour la synthèse de 2-benzoylbenzoate d'alkyle

Info

Publication number
EP4107143A1
EP4107143A1 EP21711678.9A EP21711678A EP4107143A1 EP 4107143 A1 EP4107143 A1 EP 4107143A1 EP 21711678 A EP21711678 A EP 21711678A EP 4107143 A1 EP4107143 A1 EP 4107143A1
Authority
EP
European Patent Office
Prior art keywords
reaction
phthalate
benzoylbenzoate
alkyl
phenyl magnesium
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.)
Pending
Application number
EP21711678.9A
Other languages
German (de)
English (en)
Inventor
Souvagya BISWAS
Ruth Figueroa
Muhunthan Sathiosatham
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.)
Dow Global Technologies LLC
Rohm and Haas Co
Original Assignee
Dow Global Technologies LLC
Rohm and Haas Co
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 Dow Global Technologies LLC, Rohm and Haas Co filed Critical Dow Global Technologies LLC
Publication of EP4107143A1 publication Critical patent/EP4107143A1/fr
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring

Definitions

  • the present invention relates to a process for preparing alkyl 2- benzoylbenzoate.
  • Alkyl 2-benzoylbenzoates are typically prepared by a Friedel-Crafts reaction.
  • methyl 2-benzoylbenzoate(M2BB) is conventionally prepared by a Friedel-Crafts reaction of phthalic anhydride with benzene in the presence of a stoichiometric amount of Lewis acid followed by a second step esterification reaction.
  • the esterification reaction may occur under acidic conditions with methanol in the presence of a strong acid (Vogel et. al. Practical Organic Chemistry, 5 th Ed. pp 1016).
  • the esterification reaction may occur under basic conditions with iodomethane in the presence of a base (ChemCatChem 2017, 9, 3989-3996).
  • Methyl 2-benzoylbenzoate can also be synthesized via a Palladium- catalyzed acylation chemistry between benzaldehyde and 2-halomethylbenzoate.
  • this chemistry needs expensive transition metal catalysts and a stoichiometric amount of oxidant (J. Org. Chem. 2016, 81, 6409).
  • methyl 2-benzoylbenzoate could be potentially synthesized by a Suzuki coupling between the activated amide and corresponding boronic acid ⁇ Org. Process Res. Dev. 2018, 22, 1188).
  • the present invention provides a process that addresses one or more of the problems with existing alkyl 2-benzoylbenzoate synthesis processes.
  • the present invention is directed to a process for preparing an alkyl 2- benzoylbenzoate.
  • the process comprising reacting a dialkyl phthalate with a Grignard reagent selected from phenyl magnesium bromide, phenyl magnesium chloride, phenyl magnesium iodide, and phenyl lithium in the presence of an oxygenated solvent.
  • a Grignard reagent selected from phenyl magnesium bromide, phenyl magnesium chloride, phenyl magnesium iodide, and phenyl lithium
  • FIG. 1 shows GC-FID data of the reaction of dimethyl phthalate with phenyl magnesium bromide for 16 hours according to an embodiment of the present invention.
  • FIG. 2 is a 1 H NMR spectrum of the product methyl 2-benzoylbenzoate according to an embodiment of the present invention.
  • a As used herein, the terms “a,” “an,” “the,” “at least one,” and “one or more” are used interchangeably.
  • the terms “comprises,” “includes,” “contains,” and variations thereof do not have a limiting meaning where these terms appear in the description and claims.
  • a mixture that includes a polymerization inhibitor can be interpreted to mean that the mixture comprises at least one polymerization inhibitor.
  • an alkyl 2-benzoylbenzoate is prepared in a Grignard reaction, as shown in Formula (I) below.
  • a dialkyl phthalate is reacted with a Grignard reagent in the presence of an oxygenated solvent.
  • R and R’ may be the same or different.
  • R and R’ are identical, as shown in Formula (II) below.
  • R and R’ may be independently selected from an alkyl group comprising 1 to 4 carbon atoms, such as, for example, a methyl group, an ethyl group, a propyl group, or a tert-butyl group.
  • R and R’ are independently selected from a methyl group and an ethyl group. More preferably, R and R’ are both methyl groups, and the product is methyl 2-benoylbenzoate, as shown in Formula (III) below.
  • the Grignard reagent may be selected from phenyl magnesium bromide, phenyl magnesium chloride, and phenyl magnesium iodide.
  • the Grignard reagent selectively reacts with one of the ester functionalities of the dialkyl phthalate to form an alkyl 2-benzoylbenzoate with an average 60% yield.
  • R and R’ are both methyl groups
  • the single step reaction is highly selective for methyl 2-benzoylbenzoate (12:1) and only minor quantities of byproduct (e.g., diketone) are formed. Little over-Grignard reaction was observed in the system on either the newly formed keto-carbonyl functionality or on the second ester functionality of the dimethyl phthalate.
  • the process of the present invention can be performed without the use of expensive reagents, additives, or ligands and provide significantly improved process yields compared to traditional two-step reactions.
  • oxygenated solvent examples include, but are not limited to, diethyl ether, 1 ,4-dioxane, tert-butyl methyl ether, tetrahydrofuran, and 2-methyl tetrahydrofuran.
  • the reaction is preferably run with an overall concentration of the oxygenated solvent of 0.2 to 1 .0 M.
  • the reaction is carried out at a temperature ranging from -78°C to 150°C. More preferably, the reaction is carried out at a temperature ranging from - 40°C to 100°C. Even more preferably, the reaction is carried out at a temperature ranging from 0°C to 40°C. Preferably, the reaction is carried out for at least 1 hour, preferably at least 3 hours, and more preferably at least 12 hours.
  • the compounding ratio of dialkyl phthalate and the Grignard reagent is preferably in the range of 0.90 to 3.0 moles of the dialkyl phthalate per mole of the Grignard reagent, more preferably in the range of 1 .0 to 2.75 moles of the dialkyl phthalate per mole of the Grignard reagent, still more preferably in the range of 1.25 to 2.5 moles of the dialkyl phthalate per mole of the Grignard reagent, and even more preferably in the range of 1 .4 to 1 .6 moles of the dialkyl phthalate per mole of the Grignard reagent.
  • the reaction was slowly warmed up to room temperature and kept running for another 12 h. After that, the reaction was quenched by adding 1 N HCI solution to the reaction mixture. Diethyl ether was added and the reaction mixture was transferred to a separatory funnel. The organic layer was separated and the aqueous layer was further washed with diethyl ether. The organic layers were combined and dried over MgS04. The solvent was removed under reduced pressure to yield a brownish oil which was purified by silica gel chromatography (10%-25% ethyl acetate in hexane) to yield the product methyl 2-benzoylbenzoate (49% yield) and diketone product (6% yield).
  • reaction was quenched by adding 1 N HCI solution to the reaction mixture. Diethyl ether was added and the reaction mixture was transferred to a separatory funnel. The organic layer was separated and the aqueous layer was further washed with diethyl ether. The organic layers were combined and dried over MgSC>4. The solvent was removed under reduced pressure to yield a brownish oil which was purified by silica gel chromatography (10%-25% ethyl acetate in hexane) to yield the product methyl 2-benzoylbenzoate (60% yield) and diketone product (5% yield).
  • Phenyl magnesium bromide (45 ml, 135 mmol, 1 .05 equivalence) was dropwise added over a period of 30 mins to a THF solution (600 ml, 0.2 M) of dimethyl phthalate (25.0 g, 128.8 mmol, 1 equiv.) under nitrogen atmosphere at 0 °C and the reaction was slowly warmed up to room temperature followed by mild heating to 40 °C and kept running for 12 h. Reaction aliquots were taken at 6 h and 12 h interval and the results are shown below on Table 2. At 12 h, the reaction was quenched with 1 N HCI solution and the organic layer was isolated from the aqueous layer.
  • the organic layer was concentrated down and the concentrated material was diluted with diethyl ether and hexane (3X) was added to crash out the product (see Figure 2 for 1 H NMR).
  • the aqueous layer was analyzed by UPLC- method and it showed very small amount of organic compound leached out on the aqueous layer.

Landscapes

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

Abstract

L'invention concerne un procédé de préparation d'un 2-benzoylbenzoate d'alkyle comprenant la réaction d'un phtalate de dialkyle avec un réactif de Grignard en présence d'un solvant oxygéné. Le réactif de Grignard peut être choisi parmi le bromure de phénylmagnésium, le chlorure de phénylmagnésium et l'iodure de phénylmagnésium.
EP21711678.9A 2020-02-20 2021-02-18 Voie efficace et sélective pour la synthèse de 2-benzoylbenzoate d'alkyle Pending EP4107143A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202062978860P 2020-02-20 2020-02-20
PCT/US2021/018516 WO2021168072A1 (fr) 2020-02-20 2021-02-18 Voie efficace et sélective pour la synthèse de 2-benzoylbenzoate d'alkyle

Publications (1)

Publication Number Publication Date
EP4107143A1 true EP4107143A1 (fr) 2022-12-28

Family

ID=74871821

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21711678.9A Pending EP4107143A1 (fr) 2020-02-20 2021-02-18 Voie efficace et sélective pour la synthèse de 2-benzoylbenzoate d'alkyle

Country Status (5)

Country Link
EP (1) EP4107143A1 (fr)
JP (1) JP2023514166A (fr)
KR (1) KR20220143880A (fr)
CN (1) CN115279725A (fr)
WO (1) WO2021168072A1 (fr)

Also Published As

Publication number Publication date
WO2021168072A1 (fr) 2021-08-26
JP2023514166A (ja) 2023-04-05
CN115279725A (zh) 2022-11-01
KR20220143880A (ko) 2022-10-25

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