Pteridines. Part XLII. Synthesis and properties of 8-substituted 2,4-dithiolumazines

Condensation reactions of the 5-amino-6-(subst. amino)-2,4-dithiouracils 12 and 13 with diacetyl or benzil led to the 6,7,8-trisubstituted 2,4-dithiolumazines 14 – 16 . Methylation of these compounds affected both thio functions forming various types of 2,4-bis(methylthio)lumazine derivatives depending on the nature of the substituents at C(7) and N(8). The 6,7,8-trimethyl-2,4-dithiolumazine ( 14 ) was converted into 7,8-dihydro-6,8-dimethyl–7-methylidene-2,4-bis(methylthio)pteridine ( 17 ), whereas the 8-methyl-6,7-diphenyl-(15) and the 8-(2-hydroxyethyl)-6,7-diphenyl-2,4-dithiolumazine ( 16 ) yielded the corresponding covalent inter- or intramolecular 7,8-adducts 18 – 21 . The unusual structures were proven by spectroscopic means and those of the alcohol adducts 20 and 21 , furthermore, confirmed by X-ray analysis.     

Chemistry of novolac resins. II. Reaction of model phenols with hexamethylenetetramine

It is proposed that the reactions of hexamethylenetetramine (HMTA) with 2,4-xylenol and with 2,6-xylenol occur by different pathways. The rate of reaction and the final product distribution depend on the initial xylenol : HMTA ratio and are different in the two systems. Measured by HMTA consumption, with 2,4-xylenol the reaction rate increased with increasing xylenol : HMTA ratios, whereas with 2,6-xylenol the rate of reaction decreased with increasing 2,6-xylenol : HMTA ratio. In systems which contain both 2,4- and 2,6-xylenol, a strong preference for reaction of the HMTA with the ortho site of 2,4-xylenol was noted. This preference was apparent even in mixtures in which 2,6-xylenol was present in greater amounts than 2,4-xylenol. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1389–1398, 1997     

Microbial metabolism. Part 12. Isolation, characterization and bioactivity evaluation of eighteen microbial metabolites of 4'-hydroxyflavanone

Fermentation of 4'-hydroxyflavanone (1) with fungal cultures, Beauveria bassiana (ATCC 13144 and ATCC 7159) yielded 6,3',4'-trihydroxyflavanone (2), 3',4'-dihydroxyflavanone 6-O-β-D-4-methoxyglucopyranoside (3), 4'-hydroxyflavanone 3'-sulfate (4), 6,4'-dihydroxyflavanone 3'-sulfate (5) and 4'-hydroxyflavanone 6-O-β-D-4-methoxyglucopyranoside (7). B. bassiana (ATCC 13144) and B. bassiana (ATCC 7159) in addition, gave one more metabolite each, namely, flavanone 4'-O-β-D-4-methoxyglucopyranoside (6) and 6,4'-dihydroxyflavanone (8) respectively. Cunninghamella echinulata (ATCC 9244) transformed 1 to 6,4'-dihydroxyflavanone (8), flavanone-4'-O-β-D-glucopyranoside (9), 3'-hydroxyflavanone 4'-sulfate (10), 3',4'-dihydroxyflavanone (11) and 4'-hydroxyflavanone-3'-O-β-D-glucopyranoside (12). Mucor ramannianus (ATCC 9628) metabolized 1 to 2,4-trans-4'-hydroxyflavan-4-ol (13), 2,4-cis-4'-hydroxyflavan-4-ol (14), 2,4-trans-3',4'-dihydroxyflavan-4-ol (15), 2,4-cis-3',4'-dihydroxyflavan-4-ol (16), 2,4-trans-3'-hydroxy-4'-methoxyflavan-4-ol (17), flavanone 4'-O-α-D-6-deoxyallopyranoside (18) and 2,4-cis-4-hydroxyflavanone 4'-O-α-D-6-deoxyallopyranoside (19). Metabolites 13 and 14 were also produced by Ramichloridium anceps (ATCC 15672). The former was also produced by C. echinulata. Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antiprotozoal activities against selected organisms.     

Polymerization of methacrylates. I. Polymerization reactivity of picryl methacrylate

The polymerization of picryl (PMA), 2,4-dinitrophenyl (2,4-DNMA),2,6-dinitrophenyl (2,6-DNMA), 2-methyl-4,6-dinitrophenyl (MDNMA), and 2,6-dimethylphenyl methacrylates (DMMA) was carried out in benzene at 60°C. PMA, 2,6-DNMA, and MDNMA did not undergo radical homopolymerization, while 2,4-DNMA and DMMA did. The results suggest that the growing radical readily attacks the oxygen atom of the nitro group at the 2 position of the terminal phenyl group due to the steric effect of the substituent at the 6 position, resulting in chain termination. PMA formed a charge-transfer complex with 2-naphthyl methacrylate (NMA). The stoichiometric composition of this complex was shown to be 1:1 molar complex. PMA was readily copolymerized with NMA. The amount of solvent affected the composition of the copolymer obtained at a given same mole fraction in feed. The results suggest that charge-transfer interaction between the ester groups affects the copolymerization mechanism.     

Structure of chlorinated poly(vinyl chloride). XII. Configuration and reactivity of low-molecular-weight models of poly(vinyl chloride) in the course of chlorination

The chlorination of poly(vinyl chloride) (PVC) was investigated by means of low-molecular-weight models of PVC—a dimer and trimer of PVC, viz., 2,4-dichloropentane (2,4-DCP) and 2,4,6-trichloroheptane (2,4,67-TCH). Chlorinations of stereoisomeric mixtures of 2,4-DCP and 2,4,6-TCH have revealed that the d,1 form of 2,4-DCP (syndio-2,4-DCP) is more reactive in the chlorination than the meso form of 2,4-DCP (iso-2,4-DCP), while in the case of the chlorination of 2,4,6-TCH the reactivity of stereoisomers decreases in the order iso-> hetero->syndio-2,4,6-TCH; consequently, analogous structures of stereoisomers of 2,4-DCP and 2,4,6-TCH react in a reverse order and not in the same one. The qualitative order of reactivities of stereoisomers may be correlated formally with the magnitude of their dipole moments. The reactivity of stereoisomers of 2,4-DCP and 2,4,6-TCH decreases with increasing dipole moment.     

Pyrimidine N-oxides. Preparation of 6-chloro-2,4-diaminopyrimidine 3-N-oxide and its reactions

The peroxyacid oxidation of 6-chloro-2,4-diaminopyrimidine ( 1 ) led to two products, 6-chloro-2,4-diaminopyrimidine 3-N-oxide ( 2 ) and 2,4-diamino-5,6-dichloropyrimidine 3-N-oxide ( 3 ). The assignment of structure of both of these compounds was made on the basis of ir, uv, nmr, and mass spectral data. A discussion of the pathways involved in the formation of 3 is presented.     

Natural benzofurans. Synthesis of medicagol methoxybenzofuran

A general route to 2-arylbenzofurans, consisting of reaction of an o-halogenophenol ester with a cuprous arylacetylide, was employed to synthesize medicagol methoxybenzofuran. 2,4-Diraethoxyacetophenone was converted to 2,4-dimethoxyphenylacetylene in three steps and reaction of the cuprous salt with 2-iodo-4,5-methylenedioxyphenyl acetate gave the desired 2-(2′,4′-dimethoxyphenyl)-5,6-methylenedioxybenzofuran.     

Substituted pyrimidines. II. 1,3-Dimethylisocytosine and related compounds

1,3-Dimethyl-1,2-dihydro-2-imino-4(3H)pyrimidinone (1,3-dimethylisocytosine) was prepared by methylation of 2-amino-3-methyl-4(3H)pyrimidinone and was degraded in alkaline solution to a mixture of 3-methyl-2-methylamino-4(3H)pyrimidinone, 1,3-dimethyl-2,4-(1H,3H)pyrimid-indione, 2-methylamino-l-methyl-4(1H)pyrimidinone, 1-methyl-2,4-(1H,3H)pyrimidindione and 3-methyl-2,4-(1H,3H)pyrimidindione. Thiation of the title compound gave both 1,2-dihydro-1,3-dimethyl-2-thio-4(3H)pyrimidinone and 1,3-dimethyl-2,4-(1H,3H)pyrimidinedithione. The title compound is a tautomerically fixed pyrimidine and its uv spectra were compared with related compounds, notably 3-methyl-2-dimethylarnino-4(3H)pyrimidinone which is also tautomerically fixed.     

Studies on uracil derivatives and analogs. Syntheses of 5-(βt-trimethylsilyl)ethynyluracil and 5-ethynyluracil

5-(α-Chlorovinyl)-2,4-dichloropyrimidine (I) on treatment with sodium methoxide in methanol was converted to 2,4-dimethoxy-5-ethynylpyrimidine (II) which was silylated by t-butyl lithium and chlorotrimethylsilane to 2,4-dimethoxy-5-β-trimethylsilyl)ethynylpyrimidine (IV). Compound IV on deblocking with trimethylsilyl iodide yielded 5-(β-trimethylsilyl)ethynyluracil (V), which on treatment with sodium hydroxide in methanol was converted to 5-ethynyluracil (VI).     

Dibenzyl Structuresin a Macromolecular Chain. III. Dibenzyldiisocyanates Reactivity

The reactivity of the 2,2′-, 2,4′-, 4,4′-dibenzyldiisocyanate (2,2′-, 2,4′-, 4,4′-DBDI) with n-butanol in benzene has been studied. The concentrations of all species were monitored by using high performance liquid chromatography (HPLC). The reactivity of 4,4′-DBDI is similar to that of 4,4′-diphenylmethanediisocyanate (4,4′-MDI). Very strong intramolecular catalytic effects were noticed in the case of 2,2′-DBDI, probably due to the variable molecular geometry. These effects are responsible for the whole reaction pattern. The 2,4′-DBDI NCO ortho and para groups reactivities are different and comparable to that of 2,4-toluylenediisocyanate (2,4-TDI).     

Chelating Polymers. III. Chelating Monomers and Polymers from s-Triazinyl Substituted Hydrazinoacetic Acids

The model chelating compounds β-[2,4-bis(dimethylamino)-s-triazin-6-yl] hydrazinoacetic acid, β-[2,4-bis(dimethylaniino)-s-triazind-yl] hydrazino-N, N-diacetic acid, 2,4-bis(dimethylamino)-s-triazin-6-yl-aminoacetic acid, and 2,4-bis(dimethylamino)-s-triazin-6-yl-iminodiacetic acid have been synthesized and characterized by composition analysis, infrared spectroscopy, and potentiometric titration data. The copper(II), nickel(II), cobalt(II), zinc(II), magnesium(II), and palladium(II) complexes of the first two model compounds, and the copper, nickel, cobalt, and zinc complexes of the third and fourth model compounds have been prepared. The infrared absorption spectra of the model compounds and their complexes were recorded for the range 3800 to 600 cm^?1, and the assignment of pertinent bands was made by comparison with reported infrared correlations. In those cases where applicable, shifts in the NH stretching vibration and carboxylate stretching vibration frequencies of the metal complexes were compared to those of the proper references and used as an indication of possible chelation effects in the metal complexes.

The aldehyde-reactable β-[2,4-diarnino-s-triazin-6-y1] hydrazinoacetic acid was also prepared and characterized; its polymers were prepared by the reaction of both the free ligand and its copper(II) complex with formaldehyde. Qualitative studies on the reaction of these polymers with metal ions and on the ease of metal ion elution from the polymers indicate that t h is a promising chelating polymer system.     

Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds

Various analogues of a new antidiabetic agent, pioglitazone (AD-4833, U-72107), were synthesized in order to study in more detail the structure-activity relationships of this class of drug. 5-(4-Pyridylalkylthiobenzyl)-2,4-thiazolidinediones (I), thia-analogues of pioglitazone, were prepared via Meerwein arylation of the alkylthioanilines (IV). 5-(4-Pyridylalkoxybenzylidene)-2,4-thiazolidinediones (IIa) and related heterocyclic analogues (IIb) were synthesized by Knoevenagel condensation of the aldehydes (VIII) with the corresponding azolidinones. Compounds I and II were evaluated for hypoglycemic and hypolipidemic activity in genetically obese and diabetic yellow KK (KKAy) mice. Several 5-[4-[2-(2-pyridyl)ethoxy]-benzylidene]-2,4- thiazolidinediones (IIa) were equipotent to pioglitazone. However, the thia-analogues (I) and the benzylideneheterocycles (IIb) had decreased activity. Catalytic hydrogenation of the 5-benzylidene analogue (14) was found to be a convenient new synthetic method for pioglitazone. The configuration of 14 is also discussed.     

Sorption of Paraquat and 2,4-D by an Oscillatoria Sp.-Dominated Cyanobacterial Mat

The present study characterises sorption of two pesticides, namely, paraquat (PQ) and 2,4-dichlorophenoxyacetic acid (2,4-D) by an Oscillatoria sp.-dominated cyanobacterial mat. Sorption of PQ onto the test mat was not significantly affected by the pH of the solution within the pH range 2–7. However, 2,4-D sorption was strongly influenced by the solution pH and was maximum at pH 2. Whereas PQ sorption increased with increase in temperature, 2,4-D sorption showed an opposite trend. The sorption of PQ and 2,4-D achieved equilibrium within 1 h of incubation, independent of concentration of pesticide and mat biomass in the solution. The pseudo-second-order kinetic model better defined PQ sorption than the pseudo-first-order model, whereas 2,4-D sorption was well defined by both the models. Sorption isotherms of both the pesticides showed L-type curve. Freundlich model more precisely defined PQ sorption than Langmuir model, thereby suggesting heterogeneous distribution of PQ binding sites onto the biomass surface. However, the Langmuir model more correctly defined 2,4-D sorption, thus, indicating homogeneous distribution of 2,4-D binding sites onto the biomass surface. The test biomass is a good sorbent for the removal of PQ because it could, independent of pH of the solution, sorb substantial amount of PQ (q _max = 0.13 mmol g⁻¹).     

Ring-opening polymerization. V. Hydroxyl-initiated polymerization of phenyl-substituted 1,3-dioxolan -2,4-diones: A model study

The reaction of C(5) phenyl-substituted 1,3-dioxolan-2,4-diones with a series of alcohols has been studied in order to obtain quantitative information relating to the role of hydroxyl initiation in the polymerization of these compounds. Results relating to both the effect of C(5) substitution and the structure of the attacking alcohol are presented. The reactions are secondorder (first-order with respect to each component) and show some of the kinetic features associated with monosubstituted 1,3,2-dioxathiolan-4-one-2-oxides. Structural effects are adequately represented in terms of Taft σ^* and E_s substituent constants. Of the parameters describing the properties of the reaction medium, the donicity concept was found to give the best correlation with rate data. It is considered that hydroxyl initiation will contribute to a relatively small extent in the polymerization of 5,5-diphenyl-1,3-dioxolan-2,4-dione and 5-methyl, 5-phenyl-1,3-dioxolan-2,4-dione but will form the basis for the major chain-growth process in 5-phenyl-1,3-dioxolan-2,4-dione.     

Formose Reactions. XXXII. Synthesis of Dl-2-C-Hydroxymethyl-3-Pentulose from Formaldehyde in N,N-Dimethylformamide-Water Mixed Solvent (II)

ABSTRACT

The carbon number of the main product and the total yield of products increased with an increase in the amount of triethylamine (TEA). Furthermore, the decrease of DL-2-C-hydroxymethyl-3-pentulose (2-H-3-P) was speeded up by increasing the TEA concentration and 2,4-bis(hydroxy-methyl)-3-pentulose (2,4-BH-3-P) increased smoothly along with the progress of the reaction. In the low formaldehyde (HCHO) concentration range (ca. 0.5 M), dihydroxyacetone (DHA) and DL-glycero-tetrulose were main products. 2-H-3-P and 2,4-BH-3-P increased with an increase in the formaldehyde concentration. Dihydroxyacetone, DL-glycero-tetrulose, 2-H-3-P and 2,4-BH-3-P were favorably obtained from a formose reaction by choosing a suitable [thiamine. HCl]/[HCHO] ratio. Under the reaction conditions reported in this paper, thiamine decomposed rapidly and lost its catalytic ability.     

Metabolic Products of Microorganisms. Part 269. 5-Phenylpentadienoic-acid derivatives from Streptomyces sp.

Two new phenylpentadienamides isolated from the culture filtrate of Streptomyces sp. were assigned the structures 5-(4-aminophenyl)penta-2,4-dienamide ( 2 ) and N²-[5-(4-aminophenyl)penta-2,4-dienoyl]-L -glutamine ( 3 ). In addition, 5-(4-aminophenyl)penta-2,4-dienoic acid ( 1 ) has been isolated, and its spectroscopic characteristics are reported for the first time. Compounds 1–3 exist in both the (2E,4E)- and (2E,4Z)-configurations. Electrospray and tandem MS, and HPLC/MS proved to be particularly suitable for the characterization of these metabolites.     

Pyrimidine derivatives and related compounds. 38. Synthesis of 1,3-oxazine-2,4-diones and their reaction with nucleophiles. Ring transformation of 1,3-oxazines to pyrimidines

5,6-Unsubstituted 1,3-oxazine-2,4-diones ( 3 ) and 6-unsubstituted 5-methyl-1,3-oxazine-2,4-diones ( 4 ) were prepared by reduction of the corresponding 6-chloro derivatives ( 1 and 2 ). Treatment of 6-chloro-3-methyl-1,3-oxazine-2,4-dione ( 1a ) with sodium azide, sodium cyanide, secondary amines and aniline gave the corresponding 6-substituted compounds ( 7, 9, 10 and 11 ) while the reaction of 1a and 2a,b with primary aliphatic amines such as methylamine and ethylamine caused a ring transformation to pyrimidine ring system giving barbituric acids ( 13a-d ).     

Quinazolines. 3*. synthesis of 6-bromo-8-chloro-sulfonylquinazoline-2,4(1h,3h)-dione and its interaction with nucleophilic reagents

6-Bromo-8-chlorosulfonylquinazoline-2,4(1H,3H)-dione was obtained from 6-bromoquinazoline-2,4(1H,3H)-dione and chlorosulfonic acid in place of the expected 6-bromo-7-chlorosulfonyl-quinazoline-2,4(1H,3H)-dione. Interaction of the product with water, alcohols, ammonia, aliphatic and heterocyclic amines gave 6-bromo-8X-quinazoline-2,4(1H,3H)-diones (X = SO₂OH, SO₂OAlk, SO₂NR¹R²), and, by reduction with SnCl₂·2H₂O in hydrochloric acid, 6-bromo-8-mercaptoquinazoline-2,4-dione was obtained.     

Quinazolines 1. Synthesis and chemical reactions of 6-chlorosulfonyl-quinazoline-2,4-diones

Treatment of quinazoline-2,4-dione and its symmetrical 1,3-dialkyl derivatives with chlorosulfonic acid gave the corresponding 6-chlorosulfonylquinazoline-2,4-diones. Reaction of the compounds obtained with nucleophilic agents (water, ammonia, aliphatic and cyclic amines) gave the corresponding free 2,4-dioxoquinazoline-6-sulfonic acids, 6-sulfamidoquinazoline-2,4-diones, and 2,4-dioxoquinazoline-6-sulfonic acid amides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 420–427, March 2008.     

Pyrimidines. 20. Novel reactions of 5-cyano-1,3-dimethyluracil. A simple synthesis of pyrido[2,3-d]pyrimidines

A reaction of 5-cyano-1,3-dimethyluracil (1, R = CN) with acetone in base afforded 1,3,7-trimethylpyrido-[2,3-d]pyrimidine-2,4(1H,3H)dione ( 9a ) in a moderate yield. From a reaction mixture of 1 (R = CN) with butanone, 1,3,6,7-tetramethyl- and 7-ethyl-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione ( 9b and 9c , respectively) were isolated in low yields. When ethyl cyanoacetate or malononitrile was used in place of the ketone in the above reaction, 7-amino-6-ethoxycarbonyl- and 7-amino-6-cyano-1,3-dimethylpyrido[2,3-d]-pyrimidine-2,4(1H,3H)-dione ( 14a and 14b , respectively) were obtained in quantitative yields. A plausible mechanism for the formation of bicyclic compounds is discussed.