TY - JOUR
T1 - Synthesis of benzodioxepinone analogues via a novel synthetic route with qualitative olfactory evaluation
AU - Drevermann, Britta
AU - Lingham, Anthony
AU - Huegel, Helmut Martin
AU - Marriott, Philip
PY - 2007
Y1 - 2007
N2 - Marine odorants represent a minor yet diverse class of substances within the fragrance industry, of which 7-methyl-2H-1,5-benzodioxepin-3(4H)-one (1) is commercially known as Calone 1951 (R), a synthetic first in the area of marine-fragrance chemistry To determine the extent to which the characteristic marine odor of Calone 1951 (R) corresponds to the substitution at the benzo portion of the molecule, a variety of aromatic substituents were incorporated into the benzodioxepi none structure (Scheme 1, Table 3). In light of the difficulty experienced in applying patented literature to deriving the analogues 12-18, particularly those with electron-withdrawing substituents, an alternative synthetic scheme was implemented for the construction of all analogues in favorable yields (Scheme 4, Table 3). Formation of the hydroxy-protected dihalo alkylating agent 24 via epoxide cleavage of epichlorohydrin (Scheme 3) allowed etherification favoring dihalo displacement and subsequent intramolecular ring closure (-> 26a-g). THP Deprotection followed by oxidation of the alcohols 27a-g to the ketones 12-18 provided a general pathway to the benzodioxepi none products. The influence of the substituent nature on odor activity revealed a diverse scope of olfactory character (Table 4).
AB - Marine odorants represent a minor yet diverse class of substances within the fragrance industry, of which 7-methyl-2H-1,5-benzodioxepin-3(4H)-one (1) is commercially known as Calone 1951 (R), a synthetic first in the area of marine-fragrance chemistry To determine the extent to which the characteristic marine odor of Calone 1951 (R) corresponds to the substitution at the benzo portion of the molecule, a variety of aromatic substituents were incorporated into the benzodioxepi none structure (Scheme 1, Table 3). In light of the difficulty experienced in applying patented literature to deriving the analogues 12-18, particularly those with electron-withdrawing substituents, an alternative synthetic scheme was implemented for the construction of all analogues in favorable yields (Scheme 4, Table 3). Formation of the hydroxy-protected dihalo alkylating agent 24 via epoxide cleavage of epichlorohydrin (Scheme 3) allowed etherification favoring dihalo displacement and subsequent intramolecular ring closure (-> 26a-g). THP Deprotection followed by oxidation of the alcohols 27a-g to the ketones 12-18 provided a general pathway to the benzodioxepi none products. The influence of the substituent nature on odor activity revealed a diverse scope of olfactory character (Table 4).
UR - http://onlinelibrary.wiley.com.ezproxy.lib.monash.edu.au/doi/10.1002/hlca.200790085/pdf
U2 - 10.1002/hlca.200790085
DO - 10.1002/hlca.200790085
M3 - Article
SN - 0018-019X
VL - 90
SP - 1006
EP - 1027
JO - Helvetica Chimica Acta
JF - Helvetica Chimica Acta
IS - 5
ER -