Approaches to the synthesis of the higher terpenes
<p>The various structural types into which the 'higher terpenes' are divided are defined; recent work on problems of their biogenesis and total synthesis is reviewed. A synthetic route to the pentacyclic structure (VII}) is proposed. The tetracyclic precursor (VI) of this this to be...
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| Format: | Thesis |
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1959
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| _version_ | 1797096085647261696 |
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| author | Leggate, P |
| author_facet | Leggate, P |
| author_sort | Leggate, P |
| collection | OXFORD |
| description | <p>The various structural types into which the 'higher terpenes' are divided are defined; recent work on problems of their biogenesis and total synthesis is reviewed. A synthetic route to the pentacyclic structure (VII}) is proposed. The tetracyclic precursor (VI) of this this to be obtained by alkylation of 10-carbethoxy-7,7-dimethyl-Δ<sup>1(9)</sup>-octalin-2-one (V) with the methylene bromide (IV, R=H or OH).</p> <p>A possible route for the preparation of this bromide is outlined (I-IV); this involves the degradation of the aromatic ring of the tricyclic ketone (II) to give the keto-acid (III). As the first stage of this synthesis, the tricyclic unsaturated ketone (I) has been prepared.</p> <p>Attempts to prepare 2,6-dihydroxynaphthalene as a possible source of 6-methoxy-1-methyl-2-tetralone, by fusing sodium 2-hydroxynaphthalene-6-sulphonate with alkali, failed. Reduction of 6-methoxynaphthalene using Raney nickel in acidic solution gave, among other products, 6-methoxytetralin which was oxidised to 6-methoxy-1-tetralone. The latter reacted with methyl magnesium iodide to give a tertiary alcohol which, in the presence of acids, gave the expected 6-methoxy-1-methyl-3,4-dihydronaphthalene, together with 6-methoxy-1-methylnaphthalene and 6-methoxy-1-methyl-tetralin, the products of its own dismutation, as reported by Jacques and Kagan. A possible mechanism for this disputation is proposed, and the effects of the conditions of dehydration on this reaction are studied. The dihydronaphthalene, when treated with lead tetra-acetate, gave a diacetate which rearranged in low yield under strongly acid conditions to 6-methoxy-1-methyl-2-tetralone. Ring extension of this tetralone gave the tricyclic ketone (I).</p> <p>Alternative methods for the preparation of 6-methoxy-1-methyl-2-teralone were investigated. Reaction of 6-methoxy-1-methyl-3,4-dihydronaphthalene with perbenzoic acid gave, not the epoxide, but a hydroxy-benzoate which was also rearranged to the required tetralone, although the yield obtained by Howell and Taylor could not be repeated. The crystalline material isolated in low yield from the product of the peracid treatment was formulated as 1-benzoyloxy-2-hydroxy-6-methoxy-1-methyltetralin; reasons for this formulation are discussed. Treatment of the dihydronaphthalene with formic acid gave an &alpha-ketol; from which 6-methoxy-1-methyl-2-teralone could not be obtained. Attempts to prepare this tetralone from 2-benzal-6-methoxy-2-teralone were unsuccessful because 1,4-addition products appeared to be formed in the Grignard reaction. Anti-Markownikoff hydration of 6-methoxy-1-methyl-3,4-dihydronaphthalene under the Brown conditions gave a product which the results of subsequent oxidation suggested to be a mixture of 6-methoxy-1-methyl-2- and 4-tetralols.</p> <p>The publication of a synthetic route very similar to that adopted in the present work resulted in the work being suspended.</p> <p>5-(2′-Bromoethyl)-6-methylene-1,1,10-trimethyl-<em>trans</em>-decalin was prepared by a route developed by Rushton. Oxidation of of sclareol with potassium permanganate gave the enol ether (VIII) which, after ozonolysis and reduction with lithium aluminium hydride, afforded the glycol (IX). The required bromide was obtained by treating the last with phosphorus oxybromide.</p> <p>10-Carbethoxy-7,7,-dimethyl-Δ<sup>1(9)</sup>-octalin-2-one, containing the potential D and E rings of the pentacyclic ststem, was synthesised from dimedone. The enol chloride derived from dimedone was reduced with lithium in liquid ammonia (30% yield) and by catalytic hydrogenation (50-70%) to 3,3-dimethylcyclohexanone, which was carbethoxylated to 2-carbethoxy-5,5-dimethylcyclohexanone. The required octalone was produced in nearly quantitative yield from this compound by ring extension.</p> <p>The products of catalytic and lithium-ammonia reduction of the octalone were compared.</p> <p>Resolutoon of the octalone was not possible when its menthhydrazone was used, but was at least partly achieved by the use of the (-)brucine salt of the <em>p</em>-carboxyphenyl-hydrazone, although the yield was poor and the method laborious.</p> <p>Conditions for alkylating the octalone without decomposition were defined in model experiments using n-propyl iodide. To obtain even small quantities of tetracyclic material under suoh conditions it was necessary to employ the iodo-derivative (IV, R=H, X=I), which is more reactive than the corresponding bromo-compound. The latter reacted if diglyme was used as the solvent, as suggested by Zook. In this reaction both the iodo- and the bromo-compounds gave two tetracyclic products; the possibility that they are the two enantiomorphs of the ketone (VI) is discussed.</p> |
| first_indexed | 2024-03-07T04:37:00Z |
| format | Thesis |
| id | oxford-uuid:d0498953-0a24-4382-ad63-6369e512c6b4 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T04:37:00Z |
| publishDate | 1959 |
| record_format | dspace |
| spelling | oxford-uuid:d0498953-0a24-4382-ad63-6369e512c6b42022-03-27T07:48:51ZApproaches to the synthesis of the higher terpenesThesishttp://purl.org/coar/resource_type/c_db06uuid:d0498953-0a24-4382-ad63-6369e512c6b4Polonsky Theses Digitisation Project1959Leggate, P<p>The various structural types into which the 'higher terpenes' are divided are defined; recent work on problems of their biogenesis and total synthesis is reviewed. A synthetic route to the pentacyclic structure (VII}) is proposed. The tetracyclic precursor (VI) of this this to be obtained by alkylation of 10-carbethoxy-7,7-dimethyl-Δ<sup>1(9)</sup>-octalin-2-one (V) with the methylene bromide (IV, R=H or OH).</p> <p>A possible route for the preparation of this bromide is outlined (I-IV); this involves the degradation of the aromatic ring of the tricyclic ketone (II) to give the keto-acid (III). As the first stage of this synthesis, the tricyclic unsaturated ketone (I) has been prepared.</p> <p>Attempts to prepare 2,6-dihydroxynaphthalene as a possible source of 6-methoxy-1-methyl-2-tetralone, by fusing sodium 2-hydroxynaphthalene-6-sulphonate with alkali, failed. Reduction of 6-methoxynaphthalene using Raney nickel in acidic solution gave, among other products, 6-methoxytetralin which was oxidised to 6-methoxy-1-tetralone. The latter reacted with methyl magnesium iodide to give a tertiary alcohol which, in the presence of acids, gave the expected 6-methoxy-1-methyl-3,4-dihydronaphthalene, together with 6-methoxy-1-methylnaphthalene and 6-methoxy-1-methyl-tetralin, the products of its own dismutation, as reported by Jacques and Kagan. A possible mechanism for this disputation is proposed, and the effects of the conditions of dehydration on this reaction are studied. The dihydronaphthalene, when treated with lead tetra-acetate, gave a diacetate which rearranged in low yield under strongly acid conditions to 6-methoxy-1-methyl-2-tetralone. Ring extension of this tetralone gave the tricyclic ketone (I).</p> <p>Alternative methods for the preparation of 6-methoxy-1-methyl-2-teralone were investigated. Reaction of 6-methoxy-1-methyl-3,4-dihydronaphthalene with perbenzoic acid gave, not the epoxide, but a hydroxy-benzoate which was also rearranged to the required tetralone, although the yield obtained by Howell and Taylor could not be repeated. The crystalline material isolated in low yield from the product of the peracid treatment was formulated as 1-benzoyloxy-2-hydroxy-6-methoxy-1-methyltetralin; reasons for this formulation are discussed. Treatment of the dihydronaphthalene with formic acid gave an &alpha-ketol; from which 6-methoxy-1-methyl-2-teralone could not be obtained. Attempts to prepare this tetralone from 2-benzal-6-methoxy-2-teralone were unsuccessful because 1,4-addition products appeared to be formed in the Grignard reaction. Anti-Markownikoff hydration of 6-methoxy-1-methyl-3,4-dihydronaphthalene under the Brown conditions gave a product which the results of subsequent oxidation suggested to be a mixture of 6-methoxy-1-methyl-2- and 4-tetralols.</p> <p>The publication of a synthetic route very similar to that adopted in the present work resulted in the work being suspended.</p> <p>5-(2′-Bromoethyl)-6-methylene-1,1,10-trimethyl-<em>trans</em>-decalin was prepared by a route developed by Rushton. Oxidation of of sclareol with potassium permanganate gave the enol ether (VIII) which, after ozonolysis and reduction with lithium aluminium hydride, afforded the glycol (IX). The required bromide was obtained by treating the last with phosphorus oxybromide.</p> <p>10-Carbethoxy-7,7,-dimethyl-Δ<sup>1(9)</sup>-octalin-2-one, containing the potential D and E rings of the pentacyclic ststem, was synthesised from dimedone. The enol chloride derived from dimedone was reduced with lithium in liquid ammonia (30% yield) and by catalytic hydrogenation (50-70%) to 3,3-dimethylcyclohexanone, which was carbethoxylated to 2-carbethoxy-5,5-dimethylcyclohexanone. The required octalone was produced in nearly quantitative yield from this compound by ring extension.</p> <p>The products of catalytic and lithium-ammonia reduction of the octalone were compared.</p> <p>Resolutoon of the octalone was not possible when its menthhydrazone was used, but was at least partly achieved by the use of the (-)brucine salt of the <em>p</em>-carboxyphenyl-hydrazone, although the yield was poor and the method laborious.</p> <p>Conditions for alkylating the octalone without decomposition were defined in model experiments using n-propyl iodide. To obtain even small quantities of tetracyclic material under suoh conditions it was necessary to employ the iodo-derivative (IV, R=H, X=I), which is more reactive than the corresponding bromo-compound. The latter reacted if diglyme was used as the solvent, as suggested by Zook. In this reaction both the iodo- and the bromo-compounds gave two tetracyclic products; the possibility that they are the two enantiomorphs of the ketone (VI) is discussed.</p> |
| spellingShingle | Leggate, P Approaches to the synthesis of the higher terpenes |
| title | Approaches to the synthesis of the higher terpenes |
| title_full | Approaches to the synthesis of the higher terpenes |
| title_fullStr | Approaches to the synthesis of the higher terpenes |
| title_full_unstemmed | Approaches to the synthesis of the higher terpenes |
| title_short | Approaches to the synthesis of the higher terpenes |
| title_sort | approaches to the synthesis of the higher terpenes |
| work_keys_str_mv | AT leggatep approachestothesynthesisofthehigherterpenes |