The main goal of the research described in this thesis was to develop appropriate routes for the synthesis of, 2,2- disubstituted adamantanes including adamantanespiroderivatives that might possess physiologically active properties.

Zie: Summary

Reiffers, Stoffer,

Reiffers, Stoffer

University of Groningen

   University of Groningen2,2-digesubstitueerde adamantanenReiffers, StofferIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1973Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Reiffers, S. (1973). 2,2-digesubstitueerde adamantanen. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019SUMMARYThe main goal of the research described in this thesiswas to develop appropriate routes for the synthesis of, 2,2-disubstituted adamantanes including adamantanespiroderiva-tives that might possess physiologically active properties.In addition attention was payed to the steric influence of theadamantane moiety on the course of the reactions.D,í(Y;-ryChapter I is an introductory chapter. Chapter II dealswith a number of condensation reactions with 2-AdCOOCH3(8),  2,2-AdBTCOOCH , 2-AdCHO and some addi t ion react ionswith methyleneadamantane derivates. These reactions gave2,2-disubstituted adamantanes in (very) poor yields whilesome failed entirelY..An exception was the addition of chlorosulphonylisocyanateto carbonyladamantane (4$ ( methanolyses of the adductyielded S).In sharp contrast, the reactions of 2-AdCOOHa with l i-thiumdiisopropylamide followed by treatment with carbon-dioxide gave the monoester of  adamantane-2,z-dicarboxyl icacid (,?.3) in a nearly quantitative yield (chapter V). Thelatter compound served as the starting material for manyother 2,  2-disubst i tuted adamantanes. To determine the scopeand limitations of this novel synthetic route to malonic acidderivates a number of carboxylic esters $rere treated inthe same way. The results u/ere promising especiallythe preparation of certain malonic acids which couldobtained with diff iculty by classical routes.In chapter IV the synthesis of a number of adamantanespi-rocyclobutane derivatives including adamantanespiro( 3t -ami-nocyclobutane) (9$ and adamantanespirocyclobutane- 2t ,3t --dione (&{) is mentioned. Adamantanespiro-2t -succinic anhy-dride (fl) served as starting material for these compounds.1 ? 0forbet r / Iin this thesisthes is  o f  2 ,2 -respiroderiva-'e propert ies.rfluence of thert ions.,apter II deals2-AdCOOCHsition reactions:eactions gaver yields whilernylisocyanateof the adduct)OHs with l i-wi th carbon-l-dicarboxylicrpter V).  The:ial for manynine the scopemalonic acidlre t reated in-'specially forr ich could beamantanespi-sp i ro (3 ' -ami -b u t a n e - 2 t  , 3 t  -rccinic anhy-)  compounds.cH2xcH2X ê_.2cH2136IIf f i--ory Ft35#:::4/'ïïï'^ .  - n3IN€M:* €g""ï /44.'C0:ïï:,r:6 s /4sï-r5l€NHz163ïff:57g:Tt:oocH364chapter vI is concerned with the preparation and pro-perties of adamantanespirocompounds with one or two nitro-gen atoms (azetidines, azetidinones and malonimidic com-pounds). The two isomeric adamantanespiroazetidinones urereprepared from the corresponding p-amino-esters.  The ami-no-esters could be obtained only with great diff iculty andin low yields f rom adamantane-2-succinic anhydr ide,  asdescr ibed in chapter I I I .o ,ceHs[ ^./rrY..i.l l l l t u \ ^ t st6ó./ottt ._During this researchfluence of the adamantyltane derivatives wereseveral examples of the steric in-group on the reactivity of adaman-observed. The c- carbon atoms ofT7L2, 2-disubstituted compounds strongly resemble neopentylictype atoms. In this respect the low reactivit;r of 2,2-dil(to-sylmethyl)adamantane (chapter II) and adamantane- 2, 2-dí-carborylic acid chloride (147; chapter VI) in nucleophilicsubstitution reactions is noteworthy.;_'-Porition gtrfi;^ Íft._*ry 3\ .Ar'\The poor results of the condensation reactions of z-Ad-COOCHg (8) with a number of bases as well as the lack ofreactivity of some methyleneadamantanes with electrophilespoint to a considerable steric hindrance on the 2-positionof, 2-substituted adamantanes.Finally in addition to the adamantane research, chapter VIIdeals with the smooth conversion of bistrimethylsiloryalkeneswith bromine to cyclobutane- 1, 2-diones and other ediones.This valuable reaction \ilas developed during the synthesisof adamantanespirocyclobutane- 2t ,3t -dione (34 .The cyclobutane- 1, 2-diones, from which the correspondingquinoxalines could be obtained, appeared to be very sensitiveto moisture as was shown by the rapid conversion to c-hy-drorycyclopropane carborylie acids.t72r(tJI

2,2-digesubstitueerde adamantanen

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The main goal of the research described in this thesis was to develop appropriate routes for the synthesis of, 2,2- disubstituted adamantanes including adamantanespiroderivatives that might possess physiologically active properties. Zie: Summar

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ARTS repository - University of Groningen

   University of Groningen2,2-digesubstitueerde adamantanenReiffers, StofferIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1973Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Reiffers, S. (1973). 2,2-digesubstitueerde adamantanen. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 09-09-2023SUMMARYThe main goal of the research described in this thesiswas to develop appropriate routes for the synthesis of, 2,2-disubstituted adamantanes including adamantanespiroderiva-tives that might possess physiologically active properties.In addition attention was payed to the steric influence of theadamantane moiety on the course of the reactions.D,í(Y;-ryChapter I is an introductory chapter. Chapter II dealswith a number of condensation reactions with 2-AdCOOCH3(8),  2,2-AdBTCOOCH , 2-AdCHO and some addi t ion react ionswith methyleneadamantane derivates. These reactions gave2,2-disubstituted adamantanes in (very) poor yields whilesome failed entirelY..An exception was the addition of chlorosulphonylisocyanateto carbonyladamantane (4$ ( methanolyses of the adductyielded S).In sharp contrast, the reactions of 2-AdCOOHa with l i-thiumdiisopropylamide followed by treatment with carbon-dioxide gave the monoester of  adamantane-2,z-dicarboxyl icacid (,?.3) in a nearly quantitative yield (chapter V). Thelatter compound served as the starting material for manyother 2,  2-disubst i tuted adamantanes. To determine the scopeand limitations of this novel synthetic route to malonic acidderivates a number of carboxylic esters $rere treated inthe same way. The results u/ere promising especiallythe preparation of certain malonic acids which couldobtained with diff iculty by classical routes.In chapter IV the synthesis of a number of adamantanespi-rocyclobutane derivatives including adamantanespiro( 3t -ami-nocyclobutane) (9$ and adamantanespirocyclobutane- 2t ,3t --dione (&{) is mentioned. Adamantanespiro-2t -succinic anhy-dride (fl) served as starting material for these compounds.1 ? 0forbet r /Iin this thesisthes is  o f  2 ,2 -respiroderiva-'e propert ies.rfluence of thert ions.,apter II deals2-AdCOOCHsition reactions:eactions gaver yields whilernylisocyanateof the adduct)OHs with l i-wi th carbon-l-dicarboxylicrpter V).  The:ial for manynine the scopemalonic acidlre t reated in-'specially forr ich could beamantanespi-sp i ro (3 ' -ami -b u t a n e - 2 t  , 3 t  -rccinic anhy-)  compounds.cH2xcH2X ê_.2cH2136IIf f i--ory Ft35#:::4/'ïïï'^ .  - n3IN€M:* €g""ï /44.'C0:ïï:,r:6 s /4sï-r5l€NHz163ïff:57g:Tt:oocH364chapter vI is concerned with the preparation and pro-perties of adamantanespirocompounds with one or two nitro-gen atoms (azetidines, azetidinones and malonimidic com-pounds). The two isomeric adamantanespiroazetidinones urereprepared from the corresponding p-amino-esters.  The ami-no-esters could be obtained only with great diff iculty andin low yields f rom adamantane-2-succinic anhydr ide,  asdescr ibed in chapter I I I .o ,ceHs[ ^./rrY..i.l l l l t u \ ^ t st6ó./ottt ._During this researchfluence of the adamantyltane derivatives wereseveral examples of the steric in-group on the reactivity of adaman-observed. The c- carbon atoms ofT7L2, 2-disubstituted compounds strongly resemble neopentylictype atoms. In this respect the low reactivit;r of 2,2-dil(to-sylmethyl)adamantane (chapter II) and adamantane- 2, 2-dí-carborylic acid chloride (147; chapter VI) in nucleophilicsubstitution reactions is noteworthy.;_'-Porition gtrfi;^ Íft._*ry 3\ .Ar'\The poor results of the condensation reactions of z-Ad-COOCHg (8) with a number of bases as well as the lack ofreactivity of some methyleneadamantanes with electrophilespoint to a considerable steric hindrance on the 2-positionof, 2-substituted adamantanes.Finally in addition to the adamantane research, chapter VIIdeals with the smooth conversion of bistrimethylsiloryalkeneswith bromine to cyclobutane- 1, 2-diones and other ediones.This valuable reaction \ilas developed during the synthesisof adamantanespirocyclobutane- 2t ,3t -dione (34 .The cyclobutane- 1, 2-diones, from which the correspondingquinoxalines could be obtained, appeared to be very sensitiveto moisture as was shown by the rapid conversion to c-hy-drorycyclopropane carborylie acids.t72r(tJI

English

   University of Groningen2,2-digesubstitueerde adamantanenReiffers, StofferIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1973Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Reiffers, S. (1973). 2,2-digesubstitueerde adamantanen. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 20-06-2022SUMMARYThe main goal of the research described in this thesiswas to develop appropriate routes for the synthesis of, 2,2-disubstituted adamantanes including adamantanespiroderiva-tives that might possess physiologically active properties.In addition attention was payed to the steric influence of theadamantane moiety on the course of the reactions.D,í(Y;-ryChapter I is an introductory chapter. Chapter II dealswith a number of condensation reactions with 2-AdCOOCH3(8),  2,2-AdBTCOOCH , 2-AdCHO and some addi t ion react ionswith methyleneadamantane derivates. These reactions gave2,2-disubstituted adamantanes in (very) poor yields whilesome failed entirelY..An exception was the addition of chlorosulphonylisocyanateto carbonyladamantane (4$ ( methanolyses of the adductyielded S).In sharp contrast, the reactions of 2-AdCOOHa with l i-thiumdiisopropylamide followed by treatment with carbon-dioxide gave the monoester of  adamantane-2,z-dicarboxyl icacid (,?.3) in a nearly quantitative yield (chapter V). Thelatter compound served as the starting material for manyother 2,  2-disubst i tuted adamantanes. To determine the scopeand limitations of this novel synthetic route to malonic acidderivates a number of carboxylic esters $rere treated inthe same way. The results u/ere promising especiallythe preparation of certain malonic acids which couldobtained with diff iculty by classical routes.In chapter IV the synthesis of a number of adamantanespi-rocyclobutane derivatives including adamantanespiro( 3t -ami-nocyclobutane) (9$ and adamantanespirocyclobutane- 2t ,3t --dione (&{) is mentioned. Adamantanespiro-2t -succinic anhy-dride (fl) served as starting material for these compounds.1 ? 0forbet r /Iin this thesisthes is  o f  2 ,2 -respiroderiva-'e propert ies.rfluence of thert ions.,apter II deals2-AdCOOCHsition reactions:eactions gaver yields whilernylisocyanateof the adduct)OHs with l i-wi th carbon-l-dicarboxylicrpter V).  The:ial for manynine the scopemalonic acidlre t reated in-'specially forr ich could beamantanespi-sp i ro (3 ' -ami -b u t a n e - 2 t  , 3 t  -rccinic anhy-)  compounds.cH2xcH2X ê_.2cH2136IIf f i--ory Ft35#:::4/'ïïï'^ .  - n3IN€M:* €g""ï /44.'C0:ïï:,r:6 s /4sï-r5l€NHz163ïff:57g:Tt:oocH364chapter vI is concerned with the preparation and pro-perties of adamantanespirocompounds with one or two nitro-gen atoms (azetidines, azetidinones and malonimidic com-pounds). The two isomeric adamantanespiroazetidinones urereprepared from the corresponding p-amino-esters.  The ami-no-esters could be obtained only with great diff iculty andin low yields f rom adamantane-2-succinic anhydr ide,  asdescr ibed in chapter I I I .o ,ceHs[ ^./rrY..i.l l l l t u \ ^ t st6ó./ottt ._During this researchfluence of the adamantyltane derivatives wereseveral examples of the steric in-group on the reactivity of adaman-observed. The c- carbon atoms ofT7L2, 2-disubstituted compounds strongly resemble neopentylictype atoms. In this respect the low reactivit;r of 2,2-dil(to-sylmethyl)adamantane (chapter II) and adamantane- 2, 2-dí-carborylic acid chloride (147; chapter VI) in nucleophilicsubstitution reactions is noteworthy.;_'-Porition gtrfi;^ Íft._*ry 3\ .Ar'\The poor results of the condensation reactions of z-Ad-COOCHg (8) with a number of bases as well as the lack ofreactivity of some methyleneadamantanes with electrophilespoint to a considerable steric hindrance on the 2-positionof, 2-substituted adamantanes.Finally in addition to the adamantane research, chapter VIIdeals with the smooth conversion of bistrimethylsiloryalkeneswith bromine to cyclobutane- 1, 2-diones and other ediones.This valuable reaction \ilas developed during the synthesisof adamantanespirocyclobutane- 2t ,3t -dione (34 .The cyclobutane- 1, 2-diones, from which the correspondingquinoxalines could be obtained, appeared to be very sensitiveto moisture as was shown by the rapid conversion to c-hy-drorycyclopropane carborylie acids.t72r(tJI

2,2-digesubstitueerde adamantanen

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