Tetramethyl Ester Research Articles

The proton magnetic resonance spectra of porphyrins—VII: Synthesis and NMR studies of thallium(III) coproporphyrin chelates

The four coproporphyrin “type-isomers” have been synthesized as their tetramethyl esters ( 1) through modifications of existing procedures. When treated with thallium(III) trifluoroacetate, these porphyrins furnish the corresponding aquo porphinatothallium(III) hydroxides ( 2) after ligand exchange induced by chromatography on deactivated alumina. The proton NMR spectra of the chloroform solutions of thallium(III) coproporphyrins show a pronounced concentration dependence, all resonances moving to low field upon dilution; the spectra of the type-III and -IV isomers show additional fine structure in solution. Both the meso- and β-Me protons show thallium-proton spin couplings. These results are interpreted in terms of a monomer-dimer equilibrium. In the dimers of the type-I and -II chelates, the rings lie directly one above another, whereas with the type-III and -IV complexes, steric repulsions of the propionate side-chains cause lateral displacement of one molecule in the dimer relative to the other, resulting in the observed fine structure in the spectra. The inter-porphyrin distances and lateral displacements are calculated on this basis and are compared with the corresponding dimers of the parent coproporphyrins, with which there are considerable similarities.

Pyrroles and related compounds. Part XXIII. Protoporphyrin-I

The synthesis of protoporphyrin-I dimethyl ester (2)via the b-oxobilane route is reported. Fractional crystallisation was unsuccessful in the separation of the dimethyl esters of protoporphyrin-I and protoporphyrin-IX and also the tetramethyl esters of coproporphyrins -I and -III; the significance of these observations, in relation to biosynthetic investigations, is discussed.

Porphyrins and bile pigments from brominated pyrromethenes.

Aetioporphyrin-I (1a) is obtained in 50–60% yield by heating 5-bromo-3,4′-diethyl-3′,4,5′-trimethylpyrromethene perbromide (4a) under reflux in formic acid, surpassing the yields from the established syntheses using the less accessible 5-bromo-5′-bromomethylpyrromethene hydrobromides (2a, b). The 5-bromo-5′-methylpyrromethene hydrobromides and one equivalent of free bromine can be used as an alternative to the crystalline perbromides; in this way a 50% yield of coproporphyrin-I tetramethyl ester (1b) has been obtained.Aetiobiliverdin-IVγ(7a) is shown to be a by-product of the aetioporphyrin-I syntheses when 98% formic acid is used as the reaction medium, and the procedure has been modified to give preparatively acceptable yields of this bile pigment.

Coproporphyrin-III from protoporphyrin-IX

Manipulation of the vinyl side-chains of the readily available protoporphyrin-IX dimethyl ester (2) allows the synthesis of coproporphyrin-III tetramethyl ester (1) in an overall yield of 37%.

Features of the mass spectrometric behavior of porphyrin systems with a voluminous substituent in the meso position

Features of the mass-spectrometric behavior of the tetramethyl ester of β-meso-(3-acetyl-2,4-dimethyl-5-pyrryl)coproporphyrin II and the dimethyl ester of α-meso-(3-acetyl-2,4-dimethyl-5-pyrryl) mesoporphyrin III, each of which contains a voluminous pyrryl radical with a conjugated ring system in the meso position, have been investigated.

Pyrroles and related compounds. Part XIII. Porphyrin synthesis through b-oxobilanes and oxophlorins (oxyporphyrins)

Condensation of 5′-benzyloxycarbonylpyrromethane-5-carboxamides with 5-benzyloxycarbonylpyrromethanes by means of phosphoryl chloride yeilds imine salts, which can be hydrolysed to well defined, crystalline b-oxobilanes. Hydrogenolysis of the two benzyloxycarbonyl groups in these compounds, followed by cyclisation with methyl orthoformate under acidic catalysis and aeration, yields oxophlorins. These oxophlorins are efficiently converted into porphyrins by acetylation, hydrogenation with elimination of acetic acid, and dehydrogenation. Three examples of this porphyrin synthesis are given, including coproporphyrin-III tetramethyl ester and mesoporphyrin-IX dimethyl ester, and its generality is discussed.

Cyclobutanetetracarboxylic dianhydride from the reaction of tetramethyl tricyclo[4,2,2,02,5]dec-9-ene-3,4,7,8-tetracarboxylate with nitric acid

The nitric acid oxidation of the tetramethyl ester of the photoproduct of maleic anhydride with benzene yielded cyclobutanetetracarboxylic dianhydride. None of the expected unsaturated bicyclo-dianhydride was obtained.

2,4-Bis-(β-hydroxypropionic Acid) Deuteroporphyrinogen IX, a Possible Intermediate between Coproporphyrinogen III and Protoporphyrin IX

Abstract 2,4-Bis-(β-hydroxypropionic acid) deuteroporphyrin IX tetramethyl ester was synthesized from trans-diacrylic deuteroporphyrin IX and crystallized. The melting point, absorption spectra in the visible region, molar extinction co-efficient, and nuclear magnetic resonance spectra are recorded. Dehydration of β-hydroxypropionic acid deuteroporphyrin IX in pyridine with p-toluenesulfonic acid resulted in a mixture of diacrylic acid deuteroporphyrin IX and monohydroxypropionic-monoacrylic deuteroporphyrin IX. No protoporphyrin IX was formed by this method. Chromic acid-pyridine oxidation of β-hydroxypropionic acid deuteroporphyrin IX gave a diacetyl deuteroporphyrin IX. Protoporphyrin IX was obtained in a yield of 45% from an acid-catalyzed reaction of β-hydroxypropionic acid deuteroporphyrinogen IX. Diacrylic deuteroporphyrin and monovinyl-monoacrylic deuteroporphyrin IX was obtained from β-hydroxypropionic acid deuteroporphyrinogen IX at 38° and neutral pH. Protoporphyrin IX was formed from β-hydroxypropionic acid deuteroporphyrinogen IX, but not from the oxidized form, in neutral anaerobic incubation with a mitochondrial enzyme. It is suggested that β-hydroxypropionic acid deuteroporphyrinogen IX, resulting from an oxygenase-type reaction, is dehydrated and decarboxylated to protoporphyrinogen IX.

The proton magnetic resonance spectra of porphyrins. Part IV. Coproporphyrin tetramethyl esters

Comparison of the n.m.r. spectra of the coproporphyrin I, II, III, and IV tetramethyl esters in trifluoroacetic acid and chloroform solution allows an unambiguous distinction between these isomers. The spectra of the chloroform solutions show a pronounced concentration dependence, all the peaks moving to low field on dilution; the spectra of the type III and IV isomers show additional fine structure in concentrated solution. These results can be interpreted quantitatively in terms of an equilibrium between mono- and di-meric forms. In the dimer the porphyrin rings are parallel to each other and spaced ca. 8 A apart, owing to steric repulsions of the substituent propionate ester groups. With the centrosymmetrical I and II isomers the rings lie directly above one another, and no fine structure is observed, whereas with the less symmetrical III and IV isomers the steric repulsions due to the side chains cause small lateral displacements of the rings relative to one another, and hence give rise to the fine structure observed in their spectra. The size and direction of this lateral displacement may be calculated from the spectra, and is in good agreement with the model of the complex.

Transformations of tetraethyl ester of butane-1,4- Dithioboronic acid under the influence of amines

1. The reaction of ethyl thioborate with the tetramethyl ester of butane-1,4-diboronic acid gives the tetraethyl ester of butane-1,4-dithioboronic acid. 2. The reaction of primary amines with the tetraethyl ester of butane-1,4-dithioboronic acid leads to the formation of heterocyclic compounds, containing carbon, boron, and nitrogen atoms in the ring. 3. The reaction of secondary amines with the tetraethyl ester of butane-1,4-dithioboronic acid makes it possible to obtain either 1,4-bis(dialkylaminoethylmercaptoboronyl)butanes or 1,4-di[bis(dialkylamino)boronyl]butanes.

Esters of propane-1,3-diboric and propane-1,3-dithioboric acids

1. The polymer formed by hydroborating boron-trialkyl reacts with methyl borate, giving the tetramethyl ester of propane-1,3-diboric acid. 2. 1,5-Dialkoxy-1,5-diborocyclooctane reacts with orthoborates with formation of esters of propane-1,3-di-boric acid. 3. The tetramethyl and tetraethyl esters of propane-1,3-dithioboric acid were obtained from the tetramethyl ester of propane-1,3-diboric acid.

The basicities of the nitrogen atoms in the porphyrin nucleus; their dependence on some substituents of the tetrapyrrolic ring

Porphyrins have been shown to be stronger bases than previously supposed, two protons being added in two stages to the nitrogen atom s in the conjugated tetrapyrrolic ring as the pH of an aqueous solution is decreased from pH 12 to 0. The existence of mono-cations of certain porphyrins in aqueous solution with characteristic visible and ultra-violet absorption spectra has been established, p K ' a values for the two more basic ring nitrogen atoms of coproporphyrin I, deuteroporphyrin IX dimethyl ester disulphonic acid, N -methyl coproporphyrin I free acid and its tetram ethyl ester have been determ ined by spectrophotom etric titratio n in various buffer systems. Inform ation on the basicity of uroporphyrin I and mesoporphyrin IX is also included. N -Methyl coproporphyrin has been prepared. The relationship of these p K ' a values to the therm odynamic dissociation constants is discussed. Comparison of the p K ' values obtained has led to certain conclusions regarding the effect on its basicity of some substituents of the tetrapyrrolic ring, and possible structures for the free bases and cations are considered in the light of these findings.

The basicities of the nitrogen atoms in the porphyrin nucleus; their dependence on some substituents of the tetrapyrrolic ring

Porphyrins have been shown to be stronger bases than previously supposed, two protons being added in two stages to the nitrogen atoms in the conjugated tetrapyrrolic ring as the pH of an aqueous solution is decreased from pH 12 to 0. The existence of mono-cations of certain porphyrins in aqueous solution with characteristic visible and ultra-violet absorption spectra has been established, p K' a values for the two more basic ring nitrogen atoms of coproporphyrin I, deuteroporphyrin IX dimethyl ester disulphonic acid, N -methyl coproporphyrin I free acid and its tetramethyl ester have been determined by spectrophotometric titration in various buffer systems. Information on the basicity of uroporphyrin I and mesoporphyrin IX is also included. N -Methyl coproporphyrin has been prepared. The relationship of these p K' a values to the thermodynamic dissociation constants is discussed. Comparison of the p K' values obtained has led to certain conclusions regarding the effect on its basicity of some substituents of the tetrapyrrolic ring, and possible structures for the free bases and cations are considered in the light of these findings.

Preparation of Silicic Acid Jellies for Bacteriological Purposes

FOR the preparation of jellies intended for the cultivation of micro-organisms, agar-agar is generally used. For some purposes., however, it is desirable to have an opportunity of obtaining cultures of bacteria or fungi on inorganic gels to which only known substances are added. Agar-agar is an organic substance varying in composition and containing other organic substances, which may influence the cultivation of bacteria. Attempts have been made to prepare gels, for example, of silicic acid; sodium silicate and hydrochloric acid were used for the purpose1,2,3,4. But this method entails certain difficulties. Instead we have tried to make silica gels for bacteriological purposes from ortho-silicic acid tetra-methyl ester, Si(OCH3)4. When water is added to this silico-compound, silicic acid and methanol are formed, and the solution is transformed into a firm coherent gel as clear as glass. This gel formation was observed by Grimaux5.