EP4313961A1 - Procédé de préparation d'odorisants polycycliques - Google Patents

Procédé de préparation d'odorisants polycycliques

Info

Publication number
EP4313961A1
EP4313961A1 EP21716426.8A EP21716426A EP4313961A1 EP 4313961 A1 EP4313961 A1 EP 4313961A1 EP 21716426 A EP21716426 A EP 21716426A EP 4313961 A1 EP4313961 A1 EP 4313961A1
Authority
EP
European Patent Office
Prior art keywords
butyl
formula
acetyl
formyl
methyl
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
EP21716426.8A
Other languages
German (de)
English (en)
Inventor
Bernd HÖLSCHER
Tobias Wagner
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.)
Symrise AG
Original Assignee
Symrise AG
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 Symrise AG filed Critical Symrise AG
Publication of EP4313961A1 publication Critical patent/EP4313961A1/fr
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring

Definitions

  • the invention relates to the preparation of compounds of the formula (I) which are particularly suitable for use as a fragrance.
  • fragrances with musky fragrance notes in particular those fragrances that are able to produce other interesting fragrance notes in addition to a musky fragrance note (in fragrance mixtures) and to expand the possibilities of the perfumer with their novel or original fragrance properties.
  • musky fragrance notes which are able to enter into a harmonious combination with woody and/or flowery fragrances and/or other musky fragrances.
  • the different olfactory aspects and notes should preferably be superimposed, in order thereby to produce an overall complex olfactory impression.
  • the present invention relates to a process for preparing compounds of formula (I)
  • R1, R2, R3 and R4 are each independently hydrogen, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, iso -butyl, acetyl, formyl or cyano, comprising or consisting of the following steps
  • step (C) acetylation or formylation of the intermediate of step (B), wherein steps (A) and (B) occur in a one-pot reaction.
  • the process of the present invention is not only simpler, faster and more cost-effective compared to the previous prior art processes, but at the same time also increases the yield of the compounds of formula (I) to over 70% .
  • the increase in yield was particularly surprising in that steps (A) and (B), ie the etherification and subsequent Claisen rearrangement and cyclization take place in a one-pot reaction and consequently the intermediate product obtained is not isolated.
  • a one-pot reaction or also one-pot reaction is a chemical synthesis which is characterized in that as far as possible all the required reagents and solvents are mixed in a vessel at the beginning and then allowed to react (usually with stirring/mixing and heating or cooling). Sometimes individual components are only added in the course of the operation (preferably via a dropping funnel or other dosing device). Consequently, one-pot reactions do not require the isolation of intermediates, which saves material, time, and energy. In other words, steps (A) and (B) of the present process occur without isolation of intermediates recovered in step (A).
  • the compounds of the formula (I) can optionally each be present as pure stereoisomers or as a mixture of stereoisomers.
  • a compound of formula (I) may exist as an enantiomer or a mixture of enantiomers.
  • Step (C) is preferably an acetylation of the intermediate product of step (B).
  • R1 is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl or isobutyl, preferably methyl, ethyl, isopropyl or tert-butyl and/or
  • R2 means hydrogen, methyl, formyl or acetyl, preferably hydrogen, formyl or acetyl, and/or
  • R3 means hydrogen, methyl, formyl or acetyl, preferably hydrogen, formyl or acetyl, and or
  • R4 signifies hydrogen, methyl, formyl or acetyl, preferably hydrogen, formyl or acetyl.
  • the compound of the formula (I) or one, several or all of the compounds of the formula (I) is selected or each independently selected from the group consisting of the following compounds 1 to 3:
  • Figure 1 Example of the course of the manufacturing process according to the invention
  • connection 1 connection 2 connection 3 As can be seen from Figure 1, the phenol derivative is first converted to the corresponding allyl ether derivatives (step 1). This is followed by the Claisen rearrangement with subsequent cyclization (step 2). The dihydrobenzofurans thus obtained can then be acetylated or formylated under standard conditions, for example via the Friedel-Crafts acylation or the Vilsmeier-Haack formylation.
  • steps (A) and (B) correspond to steps 1 and 2 in the exemplary figure 1) in take place in a one-pot reaction.
  • steps (A) and (B) correspond to steps 1 and 2 in the exemplary figure 1) in take place in a one-pot reaction.
  • the etherification (step A) is carried out with one or more compounds of the formula (II).
  • R5 is chlorine, iodine or bromine.
  • R5 is chlorine.
  • the etherification is carried out with 1-chloro-3-methyl-but-2-ene.
  • the phenol derivative is selected from one or more compounds of formula (III)
  • R1, R2, R3 and R4 are each independently hydrogen, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl , iso-butyl, acetyl, formyl or cyano.
  • the aromatic alcohol is tert-butyl phenol.
  • the etherification preferably takes place at a reaction temperature of 90° C. to 130° C. In the most preferred embodiment of the invention, the etherification takes place at 110° C.
  • a base in the etherification is further preferred.
  • This is preferably selected from the group consisting of potassium carbonate, sodium acetate, potassium acetate, potassium bicarbonate, sodium carbonate or lithium carbonate. Potassium carbonate is particularly preferably used as the base.
  • the Claisen rearrangement and subsequent cyclization of the intermediate product of step (A), ie the allyl ether derivative is carried out at 170.degree. C. to 220.degree. More preferably, the Claisen rearrangement and subsequent cyclization of the allyl ether derivative from step (A) takes place at 190° C.
  • the intermediate of step (B) is distilled prior to acetylation or formylation.
  • Conventional processes which are well known to the person skilled in the art can be used here. Exemplary statements on this can be found, inter alia, in the example part of this application.
  • a solvent is used in the etherification.
  • the solvent is preferred selected from the group consisting of tetrahydrofuran, dimethylformamide, methylene chloride, 1,4-dioxane, N-methylpyrrolidone, acetonitrile, cyclohexanone, and mixtures thereof. More preferably, N-methylpyrrolidone is used as the solvent.
  • the compounds of the formula (I) are outstandingly suitable for use as fragrances and/or flavorings with a musky scent note.
  • the compounds of the formula (I) can be used alone or together with other fragrances and/or flavorings for the production of, for example, (perfumed) articles, e.g.
  • N-Methylpyrrolidone (81.6 g, 0.816 mol), potassium carbonate (27.4 g, 0.193 mol), tert-butylphenol (25.0 g, 0.165 mol) are initially introduced with vigorous stirring at room temperature.
  • the reaction mixture is heated to a bottom temperature of 110° C. and then 1-chloro-3-methyl-but-2-ene (29.3 g, 0.249 mol) is metered in over a period of 8 hours. This is followed by an after-reaction time of 2 hours at the same bottom temperature.
  • the reaction solution from Example 1 is treated directly (one-pot reaction) with N-methylpyrrolidone (52.5 g, 0.087 mol) and acetic acid (5.2 g, 0.087 mol). The bottom temperature is then heated to 190° C. and the low boilers are distilled off. An after-reaction time of 8 hours follows at the same bottom temperature. Thereafter, 100 ml of MTBE are added to the reaction solution at room temperature, and the organic phase is washed twice with 100 ml of 10% NaCl and concentrated on a rotary evaporator. The crude product (50.0 g) is distilled in a Kugelrohr distillation system.
  • Acetyl chloride (13.3 g, 0.170 mol) is added dropwise, with cooling, to a suspension of dichloromethane (85 g) and aluminum chloride (25.6 g, 0.192 mol).
  • the distillate from Example 2 (40.0 g, 0.160 mol) is then metered in up to a maximum reaction temperature of 20° C. and stirred overnight at the same temperature.
  • 100 g of dichloromethane and water are then added to the reaction solution while cooling with ice.
  • the organic phase is neutralized and concentrated.
  • the crude product 39.2 g is distilled in a Kugelrohr distillation system.

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 de composés de formule (I), (I) dans laquelle les radicaux respectifs dans le composé de formule (I) sont les suivants : R1, R2, R3 et R4 représentent chacun indépendamment hydrogène, méthyle, éthyle, propyle, isopropyle, butyle, sec-butyle, isobutyle, acétyle, formyle ou cyano, comprenant ou consistant en les étapes suivantes : (A) l'éthérification d'un dérivé de phénol pour obtenir un dérivé éther d'allyle ; (B) et la cyclisation ultérieure de l'éther de l'étape (A) ; (C) l'acétylation ou la formylation de l'intermédiaire de l'étape (B), les étapes (A) et (B) étant effectuées dans une réaction monotope.
EP21716426.8A 2021-04-03 2021-04-03 Procédé de préparation d'odorisants polycycliques Pending EP4313961A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2021/058820 WO2022207123A1 (fr) 2021-04-03 2021-04-03 Procédé de préparation d'odorisants polycycliques

Publications (1)

Publication Number Publication Date
EP4313961A1 true EP4313961A1 (fr) 2024-02-07

Family

ID=75377817

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21716426.8A Pending EP4313961A1 (fr) 2021-04-03 2021-04-03 Procédé de préparation d'odorisants polycycliques

Country Status (5)

Country Link
EP (1) EP4313961A1 (fr)
JP (1) JP2024514789A (fr)
KR (1) KR20230165314A (fr)
CN (1) CN117062807A (fr)
WO (1) WO2022207123A1 (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2192010T3 (es) * 1998-10-26 2003-09-16 Firmenich & Cie Nuevas cetonas biciclicas y su utilizacion en el ambito de la perfumeria.
CN102753018A (zh) * 2010-02-10 2012-10-24 Mapi医药公司 苯并呋喃的制备及其作为合成中间体的用途
EP2641903B1 (fr) 2012-03-19 2014-10-22 Symrise AG Dérivés de dihydrobenzofuranes en tant que parfums et/ou arômes

Also Published As

Publication number Publication date
WO2022207123A1 (fr) 2022-10-06
KR20230165314A (ko) 2023-12-05
JP2024514789A (ja) 2024-04-03
CN117062807A (zh) 2023-11-14

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