Solvent-free synthesis of bisferrocenylimines and their coordination to rhodium (I)
- Authors: Kleyi, Phumelele Eldridge
- Date: 2009
- Subjects: Organic compounds -- Synthesis , Organic solvents , Solution (Chemistry) , Chemistry, Organic , Coordination compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10393 , http://hdl.handle.net/10948/1053 , Organic compounds -- Synthesis , Organic solvents , Solution (Chemistry) , Chemistry, Organic , Coordination compounds
- Description: Solvent-free reactions possess advantages compared to the solvent route, such as shorter reaction times, less use of energy, better yields, etc. Herein, the synthesis and characterization of bisferrocenylimines and arylbisamines are described. Reduction of the above compounds with LAH resulted in the formation of bisferrocenylamines and arylbisamines, respectively. The coordination chemistry of all the above compounds to rhodium(I) is also discussed in the prepared complexes [Rh(COD)(NN)]ClO4, where NN = bisferrocenylimines, and [Rh(COD)(NN)]BF4, where NN = bisferrocenylamines and arylbisamines. X-ray crystal structures of the complexes [Rh(COD)(NN)]ClO4 ([3.2] and [3.3]) have been obtained. Complexes of the type [Rh(COD)(NN)]BF4 were characterized with IR and UV-vis spectroscopy, cyclic voltammetry and conductometry. The catalytic activity of the complexes was also investigated: [Rh(COD)(NN)]ClO4 for the polymerization of phenylacetylene and [Rh(COD)(NN)]BF4 for the hydroformylation of styrene.
- Full Text:
- Date Issued: 2009
- Authors: Kleyi, Phumelele Eldridge
- Date: 2009
- Subjects: Organic compounds -- Synthesis , Organic solvents , Solution (Chemistry) , Chemistry, Organic , Coordination compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10393 , http://hdl.handle.net/10948/1053 , Organic compounds -- Synthesis , Organic solvents , Solution (Chemistry) , Chemistry, Organic , Coordination compounds
- Description: Solvent-free reactions possess advantages compared to the solvent route, such as shorter reaction times, less use of energy, better yields, etc. Herein, the synthesis and characterization of bisferrocenylimines and arylbisamines are described. Reduction of the above compounds with LAH resulted in the formation of bisferrocenylamines and arylbisamines, respectively. The coordination chemistry of all the above compounds to rhodium(I) is also discussed in the prepared complexes [Rh(COD)(NN)]ClO4, where NN = bisferrocenylimines, and [Rh(COD)(NN)]BF4, where NN = bisferrocenylamines and arylbisamines. X-ray crystal structures of the complexes [Rh(COD)(NN)]ClO4 ([3.2] and [3.3]) have been obtained. Complexes of the type [Rh(COD)(NN)]BF4 were characterized with IR and UV-vis spectroscopy, cyclic voltammetry and conductometry. The catalytic activity of the complexes was also investigated: [Rh(COD)(NN)]ClO4 for the polymerization of phenylacetylene and [Rh(COD)(NN)]BF4 for the hydroformylation of styrene.
- Full Text:
- Date Issued: 2009
Novel camphor derivatives as potential asymmetric alkylation auxiliaries
- Authors: Skiti-Mama, Neliswa
- Date: 2008
- Subjects: Alkylation , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10372 , http://hdl.handle.net/10948/1077 , Alkylation , Chemistry, Organic
- Description: The investigation has been focussed on the synthesis and characterisation of camphor-derived chiral auxiliaries that incorporate two camphor skeletons and an evaluation of their stereodirecting potential in ester α-benzylation reactions. Two regioisomeric camphorquinone-derived monoketals were synthesised and identified by 1D- and 2D-NMR, and X-ray crystallography. The stereo-directing potential of the alcohols that resulted from reduction of these ketones as chiral auxiliaries in the alkylation of carboxylate ester derivatives has been studied. The diastereoselectivities shown by NMR spectroscopy range from 14- 30 % d.e. for (1R,2 S, 3R) -2 ,2-[ (1R, 2 S, 3R) -bornane-2,3-dioxy] - bornan-3-ol and 68-74 % d.e. for (1R, 2S ,3R) -3 ,3-[ (1R, 2S ,3R) - bornane-2, 3 -dioxy]bornan-2-ol with selectivities that correlate with the size of the alkyl group in the ester moiety. Trapping of the enolates generated from (1R, 2S ,3R)-2, 2 -[(1R,2 S, 3R) -bornane- 2,3-dioxy]bornan-3-yl propanoate afforded both E- and Z-silyl ketene acetal derivatives in the ratio of 64:36 confirming the formation of both possible enolate structures during enolization. Chiral auxiliaries containing a hemiaminal ether blocking group as well as two chiral alcohols containing monothio-ketal blocking groups have also been synthesised. α-Benzylation of their corresponding propanoate esters afforded the alkylated product with disappointingly low diastereos electivities. Asymmetric reduction of α-keto esters attached to (1R, 2 S, 3R) - 2,2- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-3-ol and (1R, 2S ,3R) - 3,3- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-2-ol with metal hydrides proceeded with selectivities of up to 30 % d.e. Modelling of the keto ester derivatives at DFT levels provided useful insights into possible conformations adopted by the two α-keto esters and hence the preferred face of attack by metal hydride during reduction.
- Full Text:
- Date Issued: 2008
- Authors: Skiti-Mama, Neliswa
- Date: 2008
- Subjects: Alkylation , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10372 , http://hdl.handle.net/10948/1077 , Alkylation , Chemistry, Organic
- Description: The investigation has been focussed on the synthesis and characterisation of camphor-derived chiral auxiliaries that incorporate two camphor skeletons and an evaluation of their stereodirecting potential in ester α-benzylation reactions. Two regioisomeric camphorquinone-derived monoketals were synthesised and identified by 1D- and 2D-NMR, and X-ray crystallography. The stereo-directing potential of the alcohols that resulted from reduction of these ketones as chiral auxiliaries in the alkylation of carboxylate ester derivatives has been studied. The diastereoselectivities shown by NMR spectroscopy range from 14- 30 % d.e. for (1R,2 S, 3R) -2 ,2-[ (1R, 2 S, 3R) -bornane-2,3-dioxy] - bornan-3-ol and 68-74 % d.e. for (1R, 2S ,3R) -3 ,3-[ (1R, 2S ,3R) - bornane-2, 3 -dioxy]bornan-2-ol with selectivities that correlate with the size of the alkyl group in the ester moiety. Trapping of the enolates generated from (1R, 2S ,3R)-2, 2 -[(1R,2 S, 3R) -bornane- 2,3-dioxy]bornan-3-yl propanoate afforded both E- and Z-silyl ketene acetal derivatives in the ratio of 64:36 confirming the formation of both possible enolate structures during enolization. Chiral auxiliaries containing a hemiaminal ether blocking group as well as two chiral alcohols containing monothio-ketal blocking groups have also been synthesised. α-Benzylation of their corresponding propanoate esters afforded the alkylated product with disappointingly low diastereos electivities. Asymmetric reduction of α-keto esters attached to (1R, 2 S, 3R) - 2,2- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-3-ol and (1R, 2S ,3R) - 3,3- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-2-ol with metal hydrides proceeded with selectivities of up to 30 % d.e. Modelling of the keto ester derivatives at DFT levels provided useful insights into possible conformations adopted by the two α-keto esters and hence the preferred face of attack by metal hydride during reduction.
- Full Text:
- Date Issued: 2008
Practical and scalable synthesis of N-Alkyl-N,N'Diacylhydrazines
- Authors: Gouws, Melissa Claire
- Date: 2008
- Subjects: Chemistry, Organic , Acylation , Insecticides
- Language: English
- Type: Thesis , Doctoral , DTech
- Identifier: vital:10406 , http://hdl.handle.net/10948/696 , Chemistry, Organic , Acylation , Insecticides
- Description: The work presented in this thesis is concerned with the evaluation of potential synthetic routes for the diacylhydrazine group of compounds, and particularly, unsymmetrical diacylhydrazines. Diacylhydrazines form the basis for a relatively new group of insecticides that have molt accelerating properties, and which are considered to offer substantial advantages over other insecticides used for the control of certain insects. The overall objective for this study is to evaluate different potential synthetic routes for a model diacylhydrazine with the view to define potentially scaleable routes. The compound selected for this study was the unsymmetrical diacylhydrazine, N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)-carboxamide since it offers the same range of challenges that would be expected for the synthesis of other similar unsymmetrical diacylhydrazines. Thus, the synthesis of unsymmetrical diacylhydrazines require two reaction steps: The first step is the synthesis of the intermediate mono-acylhydrazine, while the second step is the synthesis of the desired diacylhydrazine from the intermediate mono-acylhydrazine. The most important factor in the two-step reaction sequence is to obtain a high degree of selectivity for the desired mono-acylhydrazine isomer. Acylation of t-butylhydrazine using 4-methylbenzoyl chloride can produce the desired product N-[(tert-butyl)amino](4-methylphenyl)carboxamide in yields above 90 percent, but this reaction produces a variety of by-products, including the “wrong” isomer (N-amino-N- (tert-butyl)(4-methylphenyl)carboximide). Unexpected byproducts for this particular acylation reaction, not previously reported in the literature have also been identified during this investigation. This includes a de-butylated diacylhydrazine, (4-methylphenyl)- N-[(4-methylphenyl)carbonylamino] carboxamide. Although the reaction between tert-butylhydrazine and 4-methylbenzaldehyde is very selective giving near quantitative yields of the desired hydrazone, the subsequent conversion of the hydrazone into the desired mono-acylhydrazine is problematic. The most promising route appears via bromination to form the hydrazidic bromide, followed by hydrolysis of the hydrazidic bromide. Yields for the bromination reaction during this investigation were somewhat higher than that reported previously in literature. Hydrolysis of the hydrazidic bromide, apparently also results in the hydrolysis of the reaction product to give an ester of the free acid (when an ester solvent is used). The synthesis of N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide was only briefly considered to evaluate essentially two approaches, namely: · The conversion of the monoacylhydrazine, N-[(tert-butyl)amino](4- methylphenyl)carboxamide, by acylating with either benzoyl chloride or methylbenzoate (gave 86 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide when benzoyl chloride was used as acylating agent); and · The one-pot conversion of the hydrazone, [(1E)-2-(4-methylphenyl)-1- azavinyl](tert-butyl)]amine, by bromination/hydrolysis and acylation. In this case, benzoyl chloride (2 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide), benzoic acid (80.67 percent N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)carboxamide) were evaluated as potential acylating agents.
- Full Text:
- Date Issued: 2008
- Authors: Gouws, Melissa Claire
- Date: 2008
- Subjects: Chemistry, Organic , Acylation , Insecticides
- Language: English
- Type: Thesis , Doctoral , DTech
- Identifier: vital:10406 , http://hdl.handle.net/10948/696 , Chemistry, Organic , Acylation , Insecticides
- Description: The work presented in this thesis is concerned with the evaluation of potential synthetic routes for the diacylhydrazine group of compounds, and particularly, unsymmetrical diacylhydrazines. Diacylhydrazines form the basis for a relatively new group of insecticides that have molt accelerating properties, and which are considered to offer substantial advantages over other insecticides used for the control of certain insects. The overall objective for this study is to evaluate different potential synthetic routes for a model diacylhydrazine with the view to define potentially scaleable routes. The compound selected for this study was the unsymmetrical diacylhydrazine, N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)-carboxamide since it offers the same range of challenges that would be expected for the synthesis of other similar unsymmetrical diacylhydrazines. Thus, the synthesis of unsymmetrical diacylhydrazines require two reaction steps: The first step is the synthesis of the intermediate mono-acylhydrazine, while the second step is the synthesis of the desired diacylhydrazine from the intermediate mono-acylhydrazine. The most important factor in the two-step reaction sequence is to obtain a high degree of selectivity for the desired mono-acylhydrazine isomer. Acylation of t-butylhydrazine using 4-methylbenzoyl chloride can produce the desired product N-[(tert-butyl)amino](4-methylphenyl)carboxamide in yields above 90 percent, but this reaction produces a variety of by-products, including the “wrong” isomer (N-amino-N- (tert-butyl)(4-methylphenyl)carboximide). Unexpected byproducts for this particular acylation reaction, not previously reported in the literature have also been identified during this investigation. This includes a de-butylated diacylhydrazine, (4-methylphenyl)- N-[(4-methylphenyl)carbonylamino] carboxamide. Although the reaction between tert-butylhydrazine and 4-methylbenzaldehyde is very selective giving near quantitative yields of the desired hydrazone, the subsequent conversion of the hydrazone into the desired mono-acylhydrazine is problematic. The most promising route appears via bromination to form the hydrazidic bromide, followed by hydrolysis of the hydrazidic bromide. Yields for the bromination reaction during this investigation were somewhat higher than that reported previously in literature. Hydrolysis of the hydrazidic bromide, apparently also results in the hydrolysis of the reaction product to give an ester of the free acid (when an ester solvent is used). The synthesis of N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide was only briefly considered to evaluate essentially two approaches, namely: · The conversion of the monoacylhydrazine, N-[(tert-butyl)amino](4- methylphenyl)carboxamide, by acylating with either benzoyl chloride or methylbenzoate (gave 86 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide when benzoyl chloride was used as acylating agent); and · The one-pot conversion of the hydrazone, [(1E)-2-(4-methylphenyl)-1- azavinyl](tert-butyl)]amine, by bromination/hydrolysis and acylation. In this case, benzoyl chloride (2 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide), benzoic acid (80.67 percent N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)carboxamide) were evaluated as potential acylating agents.
- Full Text:
- Date Issued: 2008
Synthesis, properties and reactions of Novel Quinone Methides
- Authors: Taljaard, Jana Heloïse
- Date: 2007
- Subjects: Quinone , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10408 , http://hdl.handle.net/10948/616 , Quinone , Chemistry, Organic
- Description: Novel p-quinone methides have been synthesized by the dealkylation of 5-(p-alkyloxyaryl)- 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ols and related compounds. Aspects of the dealkylation reaction were investigated using computational methods in order to identify possible intermediates and postulate reasons for the observed reactivity patterns. This included studying the effect of varying the size of the central B-ring, changing the alkyloxy group, and altering the substitution pattern on the parent alcohols. We have assessed the relative energies of reaction intermediates and have also evaluated the influence of factors such as charge delocalisation, LUMO properties of the carbocations and thermodynamic factors on the dealkylation reaction. The use of different dealkylating reagents was also briefly investigated. Demethylation of 1,3- dimethyl-11-(4-methoxyphenyl)-6,11-dihydrodibenzo[b,e]oxepin-11-ol with pyridine hydrochloride led to acid-catalyzed ring-contraction of the parent alcohol to form a novel substituted anthraquinone, 9-(4-hydroxyphenyl)-1,3-dimethyl-anthracen-10-(9H)-one, in good yield. The general reactivity of the p-quinone methides of interest to us was explored by subjecting these compounds to reaction with a range of nucleophiles (bases, Grignard reagents and alcohols). A range of aryl Grignard reagents were reacted with the p-quinone methides, with the main product isolated in almost all cases being the aryl-coupled 1,2-addition product. The nucleophilic addition reactions of alcohols were supported by a computational study and a probable reaction mechanism has been postulated. A base-catalyzed rearrangement is proposed to account for the formation of products in which dehydrogenation of the ethane bridge was observed. These studies showed that in these p-quinone methides, chemical reactivity is strongly influenced by steric crowding, resulting in reversal of the normal 1,2- vs. 1,6- selectivities expected for nucleophilic addition. The ketalization process was explored further using diols and thiols. Products analogous to those obtained with the monohydric alcohols resulted from the diols, along with a series of novel bis-ethers. A range of miscellaneous reactions of 4-(dibenzo[a,d]cycloheptan-5-ylidene)cyclohexa-2,5,- dienone and related systems were investigated. Functionalization by epoxidation, dichlorocarbenation and Diels-Alder reactions, photochemical and [2+2] cycloaddition were attempted and reduction and oxidation reactions were also explored. Photochemical demethylation of an ortho-methoxyl substituent on the p-quinone methide system was observed to occur in good yield. The p-quinone methides underwent reductive coupling in the presence of Zn/AlCl3. The electronic spectra of highly conjugated carbocations were obtained and their potential as novel dyes evaluated. A low-temperature Grignard exchange reaction followed by spontaneous cyclization upon workup, was successful in synthesizing the lactone, spiro[10,11- dihydro-5H-dibenzo[a,d]cyclohepten-(3’,4’H)-phenyl-5,2’(5’H)-furan-5’-one], in one step from the starting ketone. A novel seven-membered Malachite Green dye analogue, 11-(4- dimethylamino-phenyl)-3-morpholin-4-yl-6,11-dihydro-dibenzo[b,e]oxepin-11-ol, was also synthesized and its electronic spectra compared to that of the unannulated Malachite Green dye series. All novel compounds synthesized were characterized using NMR, IR and HRMS-analysis.
- Full Text:
- Date Issued: 2007
- Authors: Taljaard, Jana Heloïse
- Date: 2007
- Subjects: Quinone , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10408 , http://hdl.handle.net/10948/616 , Quinone , Chemistry, Organic
- Description: Novel p-quinone methides have been synthesized by the dealkylation of 5-(p-alkyloxyaryl)- 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ols and related compounds. Aspects of the dealkylation reaction were investigated using computational methods in order to identify possible intermediates and postulate reasons for the observed reactivity patterns. This included studying the effect of varying the size of the central B-ring, changing the alkyloxy group, and altering the substitution pattern on the parent alcohols. We have assessed the relative energies of reaction intermediates and have also evaluated the influence of factors such as charge delocalisation, LUMO properties of the carbocations and thermodynamic factors on the dealkylation reaction. The use of different dealkylating reagents was also briefly investigated. Demethylation of 1,3- dimethyl-11-(4-methoxyphenyl)-6,11-dihydrodibenzo[b,e]oxepin-11-ol with pyridine hydrochloride led to acid-catalyzed ring-contraction of the parent alcohol to form a novel substituted anthraquinone, 9-(4-hydroxyphenyl)-1,3-dimethyl-anthracen-10-(9H)-one, in good yield. The general reactivity of the p-quinone methides of interest to us was explored by subjecting these compounds to reaction with a range of nucleophiles (bases, Grignard reagents and alcohols). A range of aryl Grignard reagents were reacted with the p-quinone methides, with the main product isolated in almost all cases being the aryl-coupled 1,2-addition product. The nucleophilic addition reactions of alcohols were supported by a computational study and a probable reaction mechanism has been postulated. A base-catalyzed rearrangement is proposed to account for the formation of products in which dehydrogenation of the ethane bridge was observed. These studies showed that in these p-quinone methides, chemical reactivity is strongly influenced by steric crowding, resulting in reversal of the normal 1,2- vs. 1,6- selectivities expected for nucleophilic addition. The ketalization process was explored further using diols and thiols. Products analogous to those obtained with the monohydric alcohols resulted from the diols, along with a series of novel bis-ethers. A range of miscellaneous reactions of 4-(dibenzo[a,d]cycloheptan-5-ylidene)cyclohexa-2,5,- dienone and related systems were investigated. Functionalization by epoxidation, dichlorocarbenation and Diels-Alder reactions, photochemical and [2+2] cycloaddition were attempted and reduction and oxidation reactions were also explored. Photochemical demethylation of an ortho-methoxyl substituent on the p-quinone methide system was observed to occur in good yield. The p-quinone methides underwent reductive coupling in the presence of Zn/AlCl3. The electronic spectra of highly conjugated carbocations were obtained and their potential as novel dyes evaluated. A low-temperature Grignard exchange reaction followed by spontaneous cyclization upon workup, was successful in synthesizing the lactone, spiro[10,11- dihydro-5H-dibenzo[a,d]cyclohepten-(3’,4’H)-phenyl-5,2’(5’H)-furan-5’-one], in one step from the starting ketone. A novel seven-membered Malachite Green dye analogue, 11-(4- dimethylamino-phenyl)-3-morpholin-4-yl-6,11-dihydro-dibenzo[b,e]oxepin-11-ol, was also synthesized and its electronic spectra compared to that of the unannulated Malachite Green dye series. All novel compounds synthesized were characterized using NMR, IR and HRMS-analysis.
- Full Text:
- Date Issued: 2007
Chemical studies of necic acid analogues
- Guthrie-Strachan, Jeffry James
- Authors: Guthrie-Strachan, Jeffry James
- Date: 1997
- Subjects: Organic acids , Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4425 , http://hdl.handle.net/10962/d1006909 , Organic acids , Chemistry, Organic
- Description: Various aldehydes have been reacted with methyl acrylate under Baylis-Hillman conditions, using DABCO as a catalyst, to afford a range of α-substituted acrylic esters containing an allylic hydroxy group. Selected Baylis-Hillman products have been brominated, hydrolysed and acetylated to afford substrates for the synthesis of necic acid analogues. The diastereo- and regioselectivity of nucleophilic attack, using sodium methylmercaptan, on the Baylis-Hillman products and selected brominated derivatives was investigated. The allylic hydroxy compounds favour conjugate addition with the generation of a new chiral centre, while the allylic bromo derivatives favour substitution (SN and SN') (S[subscript N] and S[subscript N]') with consequent loss of chirality. (E)-2-Isopropylcrotonic acid, a vital precursor in the synthesis of all stereoisomers of trachelanthic and viridifloric acid, was synthesised in an attempt to obtain the necic acid components required for total alkaloid synthesis of lycopsamine and its derivatives. This precursor and salicylic acid were then used to prepare esters of retronecine, a dihydroxy necine base obtained via extraction and consequent hydrolysis of retrorsine.
- Full Text:
- Date Issued: 1997
- Authors: Guthrie-Strachan, Jeffry James
- Date: 1997
- Subjects: Organic acids , Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4425 , http://hdl.handle.net/10962/d1006909 , Organic acids , Chemistry, Organic
- Description: Various aldehydes have been reacted with methyl acrylate under Baylis-Hillman conditions, using DABCO as a catalyst, to afford a range of α-substituted acrylic esters containing an allylic hydroxy group. Selected Baylis-Hillman products have been brominated, hydrolysed and acetylated to afford substrates for the synthesis of necic acid analogues. The diastereo- and regioselectivity of nucleophilic attack, using sodium methylmercaptan, on the Baylis-Hillman products and selected brominated derivatives was investigated. The allylic hydroxy compounds favour conjugate addition with the generation of a new chiral centre, while the allylic bromo derivatives favour substitution (SN and SN') (S[subscript N] and S[subscript N]') with consequent loss of chirality. (E)-2-Isopropylcrotonic acid, a vital precursor in the synthesis of all stereoisomers of trachelanthic and viridifloric acid, was synthesised in an attempt to obtain the necic acid components required for total alkaloid synthesis of lycopsamine and its derivatives. This precursor and salicylic acid were then used to prepare esters of retronecine, a dihydroxy necine base obtained via extraction and consequent hydrolysis of retrorsine.
- Full Text:
- Date Issued: 1997
Synthesis and conformational studies of indolizines
- Authors: George, Rosemary
- Date: 1994
- Subjects: Indole alkaloids -- Research , Organic compounds -- Synthesis , Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4367 , http://hdl.handle.net/10962/d1005032 , Indole alkaloids -- Research , Organic compounds -- Synthesis , Chemistry, Organic
- Description: The present investigation has involved a kinetic and mechanistic study of the thermal cyclization of 3-acetoxy-3-(2-pyridyl)-2-methylenepropanoate esters and related compounds to 2-substituted indolizines. Substrates for the kinetic study were prepared via the Baylis-Hillmann reaction of pyridine-2-carboxaldehydes with acrylate esters, acrylonitrile and methyl vinyl ketone. The resulting hydroxy compounds were then acetylated to afford the acetoxy derivatives, thermal cyclization of which gave the corresponding 2-substituted indolizines. The cyclization reactions was followed using 'H NMR spectroscopy and were shown to follow firstorder kinetics. The influence of the various substituents on the observed first-order rate constants has been examined and variable temperature studies have permitted evaluation of activation parameters for the formation of methyl indolizine-2-carboxylate and ethyl indolizine-2-carboxylate. An alternative route to 2-substituted indolizines via halogenated derivatives was explored and several halogenated 2-pyridyl derivatives were synthesised and their thermal cyclization to indolizines was attempted. Novel 5-methylindolizine-2-carboxamides were prepared as part of this investigation and dynamic NMR spectroscopy was used to study internal rotation about the amide N-CO bond in these compounds.
- Full Text:
- Date Issued: 1994
- Authors: George, Rosemary
- Date: 1994
- Subjects: Indole alkaloids -- Research , Organic compounds -- Synthesis , Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4367 , http://hdl.handle.net/10962/d1005032 , Indole alkaloids -- Research , Organic compounds -- Synthesis , Chemistry, Organic
- Description: The present investigation has involved a kinetic and mechanistic study of the thermal cyclization of 3-acetoxy-3-(2-pyridyl)-2-methylenepropanoate esters and related compounds to 2-substituted indolizines. Substrates for the kinetic study were prepared via the Baylis-Hillmann reaction of pyridine-2-carboxaldehydes with acrylate esters, acrylonitrile and methyl vinyl ketone. The resulting hydroxy compounds were then acetylated to afford the acetoxy derivatives, thermal cyclization of which gave the corresponding 2-substituted indolizines. The cyclization reactions was followed using 'H NMR spectroscopy and were shown to follow firstorder kinetics. The influence of the various substituents on the observed first-order rate constants has been examined and variable temperature studies have permitted evaluation of activation parameters for the formation of methyl indolizine-2-carboxylate and ethyl indolizine-2-carboxylate. An alternative route to 2-substituted indolizines via halogenated derivatives was explored and several halogenated 2-pyridyl derivatives were synthesised and their thermal cyclization to indolizines was attempted. Novel 5-methylindolizine-2-carboxamides were prepared as part of this investigation and dynamic NMR spectroscopy was used to study internal rotation about the amide N-CO bond in these compounds.
- Full Text:
- Date Issued: 1994
The effects of organic perturbants on the structure of soluble collagen
- Authors: Hart, Geoffrey Joseph
- Date: 1971
- Subjects: Chemistry, Organic , Collagen
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3846 , http://hdl.handle.net/10962/d1012157 , Chemistry, Organic , Collagen
- Description: Organic solvents were used in the present study as a means of investigating the non-covalent interactions involved in the maintenance and pertubation of the three-dimensional structure of the collagen macromolecule in solution. The two main types of non-covalent interaction under consideration are hydrogen bond formation and hydrophobic effects. Elucidation of the relative importance of these factors in the maintenance of the solution structure of proteins is an area of intensive investigation and fundamental significance to biochemistry as a whole. During the past decade, considerable progress has been made towards a clearer understanding of the forces involved, and a number of different theoretical and experimental approaches have emerged. Until about 1960, hydrogen bonding was widely believed to be the dominant non-covalent interaction responsible for the maintenance of secondary and tertiary structure in many proteins. Subsequently, an increasingly important role for apolar (hydrophobic) effects was suggested by a number of authors, and at present there is no satisfactorily definitive interpretation of the available experimental evidence. The current work is based on a comparison of the effects of organic solvents on widely different substrates, namely collagen, cellulose, and the chromatographic reference material, catechin. The chromatographic mobility of catechin on cellulose may be regarded as a phenomenon which is mediated entirely by polar interaction mechanisms. The effects of various organic perturbants and of changing solvent/water ratios are readily interpreted on this basis. In the collagenous systems, however, certain results appear to require the introduction of concepts other than those relating exclusively to polar bonding affinities. The experimental evidence shows that there are cases where the enhancement of the polar interaction potential of solvent/water mixtures, in relation to catechin-cellulose systems, is accompanied by an apparent reduction of polar interaction potential of the same solvent/water mixtures with respect to soluble collagen. The anomaly outlined above will be discussed in terms of two fundamentally different theoretical assumptions. In the first of these, the mechanism of perturbant action in collagenous systems is regarded as essentially similar to that governing catechin-cellulose affinity patterns. Thus, interaction processes are all treated as polar phenomena, in which direct hydrophobic destabilization of the collagen triple helix plays no part. In an attempt to explain the effects of perturbants in both collagen and cellulose-containing systems in terms of the above assumption, two hypotheses are examined involving (1) direct polar interaction between perturbant molecules and functional groups of the protein; (2.) the possibility of an enhanced polar interaction potential of water molecules, due to lowering of the environmental dielectric constant when organic solvents are added to the systems. Within the other broad conceptual division, collagen and cellulose substrates are considered to respond in fundamentally different ways to the action of organic perturbants. As before, cellulose-catechin-solvent interactions are treated as entirely polar phenomena, and perturbant effects interpreted in terms of mechanisms such as direct solvation of the substrate, and the enhanced hydrogen bonding activity of water molecules. In contrast, perturbant lyotropic action with respect to soluble collagen i s viewed as the manifestation of a major contribution by hydrophobic interaction processes to macromolecular stability. Thus, solvents that competitively reduce the assumed entropic contribution to the stability of the collagen triple helix, are seen as potential destabilizers of the native state of the protein and inhibitors of the regeneration of co-operative structures during renaturation. Both of the above approaches are critically assessed in the light of the present work and the dominant trends apparent in the recent literature.
- Full Text:
- Date Issued: 1971
- Authors: Hart, Geoffrey Joseph
- Date: 1971
- Subjects: Chemistry, Organic , Collagen
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3846 , http://hdl.handle.net/10962/d1012157 , Chemistry, Organic , Collagen
- Description: Organic solvents were used in the present study as a means of investigating the non-covalent interactions involved in the maintenance and pertubation of the three-dimensional structure of the collagen macromolecule in solution. The two main types of non-covalent interaction under consideration are hydrogen bond formation and hydrophobic effects. Elucidation of the relative importance of these factors in the maintenance of the solution structure of proteins is an area of intensive investigation and fundamental significance to biochemistry as a whole. During the past decade, considerable progress has been made towards a clearer understanding of the forces involved, and a number of different theoretical and experimental approaches have emerged. Until about 1960, hydrogen bonding was widely believed to be the dominant non-covalent interaction responsible for the maintenance of secondary and tertiary structure in many proteins. Subsequently, an increasingly important role for apolar (hydrophobic) effects was suggested by a number of authors, and at present there is no satisfactorily definitive interpretation of the available experimental evidence. The current work is based on a comparison of the effects of organic solvents on widely different substrates, namely collagen, cellulose, and the chromatographic reference material, catechin. The chromatographic mobility of catechin on cellulose may be regarded as a phenomenon which is mediated entirely by polar interaction mechanisms. The effects of various organic perturbants and of changing solvent/water ratios are readily interpreted on this basis. In the collagenous systems, however, certain results appear to require the introduction of concepts other than those relating exclusively to polar bonding affinities. The experimental evidence shows that there are cases where the enhancement of the polar interaction potential of solvent/water mixtures, in relation to catechin-cellulose systems, is accompanied by an apparent reduction of polar interaction potential of the same solvent/water mixtures with respect to soluble collagen. The anomaly outlined above will be discussed in terms of two fundamentally different theoretical assumptions. In the first of these, the mechanism of perturbant action in collagenous systems is regarded as essentially similar to that governing catechin-cellulose affinity patterns. Thus, interaction processes are all treated as polar phenomena, in which direct hydrophobic destabilization of the collagen triple helix plays no part. In an attempt to explain the effects of perturbants in both collagen and cellulose-containing systems in terms of the above assumption, two hypotheses are examined involving (1) direct polar interaction between perturbant molecules and functional groups of the protein; (2.) the possibility of an enhanced polar interaction potential of water molecules, due to lowering of the environmental dielectric constant when organic solvents are added to the systems. Within the other broad conceptual division, collagen and cellulose substrates are considered to respond in fundamentally different ways to the action of organic perturbants. As before, cellulose-catechin-solvent interactions are treated as entirely polar phenomena, and perturbant effects interpreted in terms of mechanisms such as direct solvation of the substrate, and the enhanced hydrogen bonding activity of water molecules. In contrast, perturbant lyotropic action with respect to soluble collagen i s viewed as the manifestation of a major contribution by hydrophobic interaction processes to macromolecular stability. Thus, solvents that competitively reduce the assumed entropic contribution to the stability of the collagen triple helix, are seen as potential destabilizers of the native state of the protein and inhibitors of the regeneration of co-operative structures during renaturation. Both of the above approaches are critically assessed in the light of the present work and the dominant trends apparent in the recent literature.
- Full Text:
- Date Issued: 1971
- «
- ‹
- 1
- ›
- »