Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-05-05
1998-09-22
Dentz, Bernard
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D30792
Patent
active
058115609
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process for the production of 8.alpha.,12-oxido -13,14,15,16-tetranorlabdane.
2. Discussion of the Related Art
8.alpha.,12-Oxido-13,14,15,16-tetranorlabdane, hereinafter referred as Ambroxan, is a valuable ambergris perfume which is found in ambergris, a metabolic secretion of the sperm whale (Ullmanns Encyklopadie der technischen Chemie, Vol.20, page 283, Verlag Chemie Weinheim 1981). Ambroxan can be synthesized from sclareol by oxidative side chain degradation and subsequent reduction of the lactone formed (sclareolid) in accordance with U.S. Pat. No. 3,050,532. The conversion of sclareolid into the odorless 8.alpha.,12-dihydroxy-13,14,15,16-tetranorlabdane, hereinafter referred to in short as diol, is carried out by methods known per se, for example by reduction with lithium aluminium hydride (Helv. Chim. Acta 1950, 33, 1310), with sodium borohydride (Chem. Abstr. 57, 7316a) or with potassium borohydride/lithium chloride mixtures (Chem. Abstr. 94,15913q).
The cyclizing dehydration of the diol to Ambroxan can be carried out with acidic catalysts, for example p-toluene sulfonic acid, p-toluene sulfonic acid chloride, catalytic quantities of sulfuric acid and acidic ion exchangers, in various solvents, for example toluene, hexane, pyridine, tetrahydrofuran or methanol, preferably at boiling temperature.
U.S. Pat. No. 3,029,255 describes the use of .beta.-naphthalene sulfonic acid or alumina as dehydration catalysts in the production of Ambroxan. Besides resinification products and olefins, other secondary production are obtained in this process, so that the yield of Ambroxan is less than 77%.
JP-A-86/33184 (Takasago) describes a process for the production of Ambroxan, in which cyclization of the diol precursor is induced by special catalysts. These catalysts are acid-impregnated active white clay, alumina or silica. The acids mentioned include, above all, sulfuric acid, phosphoric acid and polyphosphoric acid. However, the Takasago process has disadvantages in regard to
a) the conversion of educt, i.e. the diol used, and/or
b) the formation of dehydration products (secondary products) and/or
c) the stereoselectivity of the ring-closing reaction (level of iso-Ambroxan formation).
The above-mentioned disadvantages of the Takasago process are avoided by the process disclosed in applicants' earlier patent application WO 90112793. Nevertheless, the process according to WO 90/12793 requires relatively high reaction temperatures. In addition, the formation of dehydration products cannot be completely avoided.
All in all, it has to be said that dehydration products occur to a more or less large extent in the processes known from the prior art for the production of Ambroxan by cyclization of the diol precursor. According to investigations carried out by applicants, these dehydration products are compounds which can be represented by formulae (I), (II) and (III): ##STR1##
The dehydration products mentioned are odorless and reduce the yield of Ambroxan obtained in the acidic cyclization of the diol precursor.
It is known from EP-A-212 254 that the compound corresponding to formula (I) can be cyclized in the presence of acidic catalysts to form Ambroxan. Nevertheless, there is nothing in the description of the patent application to show how the cyclization is carried out. In particular, the description does not mention which critical parameters have to be observed to ensure that the cyclization of (I) takes place efficiently.
A.F. Barrero et al. investigated the cyclization of two derivatives of (I) in the presence of acidic catalysts (cf. Tetrahedron, 1993, Vol. 49, No. 28, pages 6251-6262). These derivatives differ structurally from compound (I) in the fact that one of the geminal methyl groups present in (I) is replaced by a group--COOMe or --CH.sub.2 OH. The cyclization takes place satisfactorily at 0.degree. C. in the highly polar solvent nitromethane. At higher temperatures, however, 8-epi-Ambroxan is preferentially formed.
As far
REFERENCES:
patent: 3029255 (1962-04-01), Stoll
patent: 3050532 (1962-08-01), Schumacher et al.
patent: 4701543 (1987-10-01), Naef
patent: 5274134 (1993-12-01), Bruns et al.
Verstegen-Haaksma et al., Total Synthesis of (-)-Ambrox etc., Tetrahedron, vol. 50 (33), pp. 10095-10106, Aug. 15, 1994.
Tetrahedron 49(28):6251-62(1993).
J. Org. Chem.57:955-60(1992).
Chemistry and Industry 516-520(Aug. 1990).
Ullmanns Encyklopadie der technischen Chemie 20:283(Vertag Chemie, 1981).
Helv. Chim. Acta. 33:1310-12(1950).
Chem. Abstr. 57:7316a(1962).
Chem. Abstr. 94:15913q(1981).
Synthesis 216-19(1983).
Bomhard Andreas
Knuebel Georg
Markert Thomas
Dentz Bernard
Henkel Kommanditgesellschaft auf Aktien
J. Murphy Glenn E.
Jaeschke Wayne C.
Meder Martin G.
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