73206-60-7Relevant academic research and scientific papers
Process Research and Scale-Up Synthesis of 3-(4-Isobutyl-2-methylphenyl)propanal, a Safe and Uniquely Performing Perfumery Ingredient
Lovchik, Martin A.,Tse, Chi-Lam,Ellwood, Simon
, p. 2906 - 2914 (2020/12/22)
Ever since the beginning of modern perfumery, muguet (lily-of-the-valley) notes have been sought after and are now found in varying doses in practically every perfume composition, accounting for the warm, soft, and comforting facets of many fragrances. Over the past decades, Lilial and Bourgeonal have evolved to become popular and inexpensive ingredients to satisfy the high demand of such floral odors. However, the search continues for more performing ingredients, especially in this odor family. Through this effort, 3-(4-isobutyl-2-methylphenyl)propanal (Nympheal) was identified as a modern, more performing, and benign alternative to the traditional ingredients. In particular, it outperforms Lilial in a sense that it has a linden blossom, a floral aldehydic odor considered to be more natural in its character. This paper details the challenge to design an efficient synthesis for the multi-kilogram production of the fragrance ingredient Nympheal. The methyl group, strategically placed in the 2-position to ensure the biological safety of the ingredient, also introduced a level of asymmetry into the molecule resulting in regiochemical challenges to identifying potential synthetic routes. Route scouting for this initial scale-up was performed using 1-isobutyl-3-methylbenzene as a feedstock made by continuous dehydrogenation of a mixture of 3- and 5-isobutyl-1-methylcyclohex-1-ene. Different routes were explored for introduction of the propanal moiety including carbonylation, Heck reaction, and Friedel-Crafts reaction. Ultimately, 3.3 kg of Nympheal was prepared by electrophilic bromination of 1-isobutyl-3-methylbenzene, followed by reaction with magnesium and dimethylformamide to give the corresponding benzaldehyde, which was then reacted with ethyl vinyl ether by the procedure from Muller-Cunradi-Pierroh and hydrogenated to give the desired product.
PHENYL BASED COMPOUNDS SUBSTITUTED WITH ALDEHYDE MOIETIES AND THEIR USE IN PERFUMERY
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Page/Page column 37; 38, (2016/06/06)
A compound represented by the formula 1, wherein R1 is H, or when R2 and R3 is H, then R1 is CHR5CHR6CHO, CR5=CR6CHO or C(CH3)CHO, wherein R5, R6 each independently may represent H or methyl; R2 is H, or when R1 and R3 is H, then R2 is CHR5CHR6CHO, CR5=CR6CHO or C(CH3)CHO, wherein R5, R6 each independently may represent H or methyl; R3 is H, or when R1 and R2 is H, then R3 is CHR5CHR6CHO, CR5=CR6CHO or C(CH3)CHO, wherein R5, R6 each independently may represent H or methyl; and R4 is methyl or a branched or linear, saturated or unsaturated, unsubstituted or substituted (optionally with cyclopropyl groups), C2-C7 alkyl or alkenyl residue, preferentially isobutyl, isoamyl. Said compounds are useful as perfume ingredients in personal care and household care products.
