Abstract  Vapors of four chemical warfare agent (CWA) stimulants, 2-chloroethyl ethyl sulfide (CEES), diethyl malonate (DEM), dimethyl methylphosphonate (DMMP), and methyl salicylate (MeS), were detected, identified, and quantitated using a fully automated, field-deployable, miniature mass spectrometer. Samples were ionized using a glow discharge electron ionization (GDEI) source, and ions were mass analyzed with a cylindrical ion trap (CIT) mass analyzer. A dual-tube thermal desorption system was used to trap compounds on 50:50 Tenax TA/Carboxen 569 sorbent before their thermal release. The sample concentrations ranged from low parts per billion [ppb] to two parts per million [ppm]. Limits of detection (LODs) ranged from 0.26 to 5.0 ppb. Receiver operating characteristic (ROC) curves are presented for each analyte. A sample of CEES at low ppb concentration was combined separately with two interferents, bleach (saturated vapor) and diesel fuel exhaust (1%), as a way to explore the capability of detecting the simulant in an environmental matrix. Also investigated was a mixture of the four CWA simulants (at concentrations in air ranging from 270 to 380 ppb). Tandem mass (MS/MS) spectral data were used to identify and quantify the individual components.

Abstract  The syntheses, structures and biological evaluation of a series of cisplatin-like complexes containing bis(imidazole) derivatives - the so-called Joseph ligands - are described. Their cytotoxicity is discussed in terms of their polar surface area, rate of aquation, and lipophilicity. The X-ray crystal structure of the platinum diiodido derivative of dimethyl 2-(di(1H-imidazol-2-yl)methyl)malonate) is reported and compared to those of related systems. Molecular modeling studies are focused on the hydrogen bonding properties of such systems, and their relevance to antitumor activity.

Abstract  Annual Pacific Northwest International Sections/Air Waste Management Association (PNWIS/AWMA) conference (2nd), Portland, OR (USA), 14-16 Nov 1990. Sponsored by Department of Energy, Washington, DC. Fourier transform infrared spectroscopy (FTIR) provides the potential to monitor incinerator emissions remotely and passively from air-mounted (helicopter) or ground-mounted (car) locations. The objective of this work was to extend the application of remote FTIR as an incinerator monitor to simple mixtures released in the laboratory and in the field. Initial data were collected for two commonly used principal organic hazardous components (POHCs), chloroform and carbon tetrachloride. To simulate mixtures that are more difficult to identify and quantify, subsequent laboratory and field studies were performed with methanol and diethyl malonate mixtures. The sensitivity of the equipment is currently in the region of low parts-per-million-per meter of air measured. Remote FTIR was able to identify and quantify components with overlapping absorbances in the presence of interference from carbon dioxide. 1 ref., 5 figs., 4 tabs.

Abstract  To determine the potential environmental persistence and toxic effects of agent simulants Diethyl Malonate (DEM) and Methyl Salicylate (MS), plants, soils, earthworms, and oil microbial populations were exposed to projected aerosolized simulant concentrations of (approximately)100 (low) and (approximately)1000 (high) mg/m(sup 3). Both simulants exhibited biphasic residence times on foliar and soil surfaces following aerosol exposure. Half-times of DEM on soil and foliar surfaces were 1 to 3 h and 5 to 22 H, respectively, and 2 to 2 h and 5 to 31 h for the MS, respectively. Persistence was longer on the foliar surfaces than that of the soils. Both simulants proved phytotoxic to vegetation with a lower threshold of 1 to 2 (mu)m/cm(sup 2) for the MS versus that of 10 (mu)g/cm(sup 2) for the DEM. However, neither significantly affected chloroplast electron transport in vitro at concentrations of up to 100 (mu)g/mL. Results from in vitro testing of DEM indicated concentrations below 500 (mu)g/g dry soil generally did not adversely impact soil microbial activity, while the theshold was 100 (mu)g/g dry soil for MS. Earthworm bioassays indicated survival rates of 66% at soil doses of 204 (mu)g DEM/cm(sup 2) soil and 86% at soil doses of 331 (mu)g MS/cm(sup 2).

Abstract  A task-specific ionic liquid (IL, OPPh2) that bears a phosphinite weak Lewis base group in an imidazolium cation was found to efficiently catalyze the Knoevenagel condensation of arylaldehydes with malononitrile, dimethyl(diethyl)malonate, and ethyl cyanoacetate. This IL plays a dual role as both the reaction media and also catalyst, and it can be easily recovered and reused in several runs. Satisfactory results were obtained with good yields, short reaction time, and simplicity in the experimental procedure. A variety of coumarin derivatives were synthesized in this procedure.

Abstract  An iridium complex was found to be an efficient catalyst for allylic alkylation of allylic acetates with a stabilized carbon nucleophile. Two unique features of iridium complex catalysis are found. (1) Regioselective alkylation at the substituted allylic terminus: the reaction of (E)-2-alkenyl acetates or 1-substituted 2-propenyl acetates with sodium salt of diethyl malonate in the presence of a catalytic amount of [Ir(COD)Cl](2)/P(OPh)(3) (P/Ir = 1-2) gave products alkylated at the substituted allylic terminus with 95-99% selectivities. P-31 NMR and C-13 NMR revealed that a catalytically active species is Ir(COD) (P(OPh)(3))Cl. The pi-acceptor property of P(OPh)(3) promotes a carbonium ion character at the substituted allylic terminus. Therefore, the nucleophile is directed to this position. (2) Retention of Z geometry in the allylic alkylation of (Z) -2-alkenyl acetates; the reaction of (Z)-2-alkenyl acetates gave a product alkylated at the unsubstituted allylic terminus with the retention of Z geometry predominantly. Retention of Z geometry in allylic alkylation is also possible by iridium catalysis. (C) 2000 Elsevier Science Ltd All rights reserved.

Abstract  Glutathione peroxidase (GSHPx) is a critical intracellular enzyme involved in detoxification of hydrogen peroxide (H(2)O(2)) to water. In the present study we examined the susceptibility of mice with a disruption of the glutathione peroxidase gene to the neurotoxic effects of malonate, 3-nitropropionic acid (3-NP), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Glutathione peroxidase knock-out mice showed no evidence of neuropathological or behavioral abnormalities at 2-3 months of age. Intrastriatal injections of malonate resulted in a significant twofold increase in lesion volume in homozygote GSHPx knock-out mice as compared to both heterozygote GSHPx knock-out and wild-type control mice. Malonate-induced increases in conversion of salicylate to 2,3- and 2, 5-dihydroxybenzoic acid, an index of hydroxyl radical generation, were greater in homozygote GSHPx knock-out mice as compared with both heterozygote GSHPx knock-out and wild-type control mice. Administration of MPTP resulted in significantly greater depletions of dopamine, 3,4-dihydroxybenzoic acid, and homovanillic acid in GSHPx knock-out mice than those seen in wild-type control mice. Striatal 3-nitrotyrosine (3-NT) concentrations after MPTP were significantly increased in GSHPx knock-out mice as compared with wild-type control mice. Systemic 3-NP administration resulted in significantly greater striatal damage and increases in 3-NT in GSHPx knock-out mice as compared to wild-type control mice. The present results indicate that a knock-out of GSHPx may be adequately compensated under nonstressed conditions, but that after administration of mitochondrial toxins GSHPx plays an important role in detoxifying increases in oxygen radicals.

Abstract  A practical large-scale synthesis of monomethyl malonate and monoethyl malonate, which are among the most commonly applied half-esters in organic synthesis, is described, applying the highly efficient selective monohydrolysis of symmetric diesters we reported before. The optimal conditions with regard to the type of base, equivalent, co-solvents, and the reaction time have been examined for large-scale reactions. Monomethyl malonate and monoethyl malonate were obtained in high yields with near 100% purity within only half a day. The conditions of this selective monohydrolysis reaction are environmentally benign and straightforward, as it requires only water, a small proportion of a volatile co-solvent, and inexpensive reagents, and produces no hazardous by-products, and therefore the synthetic utility of this reaction in process chemistry is expected.

Abstract    Reaction of ethyl 4-chloro (and 4-bromo) acetoacetate (1 and 2) with ammonium benzyldithiocarbamate gave ethyl 3-benzyl-4-hydroxy-2-thioxothiazolidine-4-acetate (3a), which was treated with 10% hydrochloric acid to afford ethyl 3-benzyl-2-thioxo-4-thiazoline-4-acetate (4a). Reaction of 1 (and 2) with N-substituted dithiocarbamates prepared from carbon disulfide and amines, followed by treatment with 10% hydrochloric acid gave the corresponding 4-thiazolines 4a-e. Reaction of 1 (and 2) with thioacetanilide derivatives prepared from phenyl isothiocyanate and active methylene compounds such as ethyl cyanoacetate, malononitrile, ethyl malonate, and cyanoacetamide in the presence of sodium ethoxide gave 2-substituted 4-hydroxythiazolidines 9a-c and thiophene derivative 10. Treatment of 9a-c with acid gave 4-thiazolines 8a-c, which were also prepared from compound 4e, ethyl iodide, and active methylene compounds.

Abstract  Novel ethyl 2-oxo-4,6-diaryl-1,2,3,4-tetrahydropyridine-3-carboxylate and 4,6-diaryl-3,4-dihydropyridine-2(1H)-one derivatives have been synthesized from the cyclization of adducts of diethylmalonate to chalcones with ammonium acetate. The structures were established on the basis of extensive spectroscopic methods and further confirmed by X-ray crystallographic analysis. Antibacterial activity of obtained pyridones was investigated against four human pathogen microorganisms and the compounds showed poor activity. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications registered for the following free supplemental resource(s): Full experimental and spectral details.]

Abstract  A series of 6-substituted [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives 4a--z were synthesized from 5-substituted 1,3,4-thiadiazol-2-amines 5 by the following consecutive reactions: pyrimidine ring closure with bis(2,4,6-trichlorophenyl) malonate, nitration, chlorination, amination, hydrogenation and diazotization. The structure of 4 was confirmed by an alternate synthesis of 4, involving reaction of 5-substituted 2-azido-1,3,4-thiadiazole 13 with ethyl cyanoacetate, followed by the Dimroth rearrangement and ring closure. The antiallergic activities (anti-passive peritoneal anaphylaxis, anti-passive cutaneous anaphylaxis and anti-slow reacting substance of anaphylaxis activities) of the products were evaluated.

Abstract  Many enantiomerically pure products with biological activities are commonly used in the pharmaceutical industry due to their effectiveness. As such, procedures that produce stereochemically pure compounds are highly desirable. Asymmetric synthesis using chiral compounds has become the preferred way to make enantiopure material. For example, selectively synthesizing secondary alcohols that are ubiquitous in natural products and pharmaceuticals can be achieved through the catalytic asymmetric addition of an alkylzinc to an aldehyde. In the Comins group, we have developed new chiral diamines, amino alcohols, and amino phosphines to test in asymmetric reactions, such as the catalytic addition of diethylzinc to benzaldehyde, and palladium-catalyzed allylic alkylation. Each of these catalysts has a nitrogen containing heterocycle and is synthesized in a few steps from commercially available materials, such as ephedrine and (S)-nicotine. Overall, the amino alcohol derivatives provided the best results in the catalytic asymmetric addition of diethylzinc to various aldehydes, while the amino phosphines showed promise in the palladium-catalyzed allylic alkylation of racemic 1,3-diphenylpropen-2-yl acetate with dimethyl malonate. However, these nicotine-based catalysts did not show great selectivity or usefulness in other metal-catalyzed reactions, such as zinc alkynylations to aldehydes, copper-catalyzed 1,4-additions, the Henry reaction, and allylic oxidations.

Abstract    Three new metabolites, named macommelinal, macrophin and macrophic acid, were isolated from the culture broth of Macrophoma commelinae IFO 9570. Their structures were determined to be 2-(4-methoxy-6-methyl-2-oxo-2H-pyran-5-yl)ethanal, 3-methyl-2-butenoic acid (E)-[5-hydroxymethyl-4-methoxy-6-(2-methoxycarbonylethenyl)-2-oxo-2H-pyran-3-ly]methyl ester and 3-(4-methoxy-3, 5-dimethyl-2-oxo-2H-pyran-6-yl)-2-propenoic acid, respectively. 4 Acetyl-3-methoxy-5-methylbenzoic acid, now named macrophomic acid, was also isolated from a large-scale culture.The biosynthesis of the macommelin group, novel 5-substituted 2-pyrone metabolites, has been investigated by feeding experiments with [1-13C]-, [1, 2-13C2]- and [1-13C, 2-2H3]acetate and [2-13C]malonate. It was concluded that all these metabolites originated from a single straight tetraketide chain. Furthermore, the biogenetic mutual relationships of these metabolites including potential intermediates were estabished through incorporation experiments with 14C-labeled compounds.

Abstract    Aiming to prepare optically active pyrrolidines (2) which are usable as chiral additives for asymmetric syntheses via enamines, and whose absolute configurations can correspond to that of D-proline (D-3c), an exploitation of the novel synthetic scheme for 2 from L-α-amino acids (L-3) via optically active γ-amino acids (4) was studied. Reaction of (S) (-)-ditosylate ((S) (-)-10a) easily derivable from L-phenylalanine (L-3a), with diethyl potassiomalonate (3.0 eq.) in tetrahydrofuran, could directly give a mixture of (R)-pyrrolidine-2-one ((R)-12a) and (R) (-)-malonate ((R) (-)-13a) in 70-80% yield. Some mechanistic studies revealed that the malonate reaction proceeded through the regiospecific ring opening of (S) (+)-aziridine ((S) (+)-11a). Acidic hydrolysis of a crude mixture of (R)-12a and (R) (-)-13a afforded (R) (-)-4a without racemization in 49% yield based on (S) (-)-10a. The same synthetic route was applicable to L-valine (L-3b), giving (R) (+)-4b. However, (S)-4c could be obtained from L-proline (L-3c), by the treatment of (S) (-)-iodide ((S) (-)-16c) prepared from (S) (-)-ditosylate ((S) (-)-10c), with malonate anion, followed by acidic hydrolysis. (R) (-)-4a and (R) (+)-4b thus obtained were readily converted into (R) (-)-2a and (R) (+)-2b by dehydration and reduction. When the asymmetric synthesis of 4-methyl-4-phenyl-2-cyclohexenone (18) was examined by using (R) (-)-2a and (R) (+)-2b, (S) (-)-18, being antipodal to that provided by using L-proline-derived pyrrolidines (1) as chiral additives, was successfully obtained.

Abstract  GAS-LIQUID CHROMATOGRAPHY HAS BEEN USED TO INVESTIGATE THE GROUP SELECTIVITY OF 28 SOLVENTS IN THE SEPARATION OF CYCLIC AND ALIPHATIC SULFIDES FROM THE HYDROCARBONS. THE SOLVENTS CONTAINING -OH AND -NH2 GROUPS WERE THE MOST SELECTIVE IN SEPARATING THE CYCLIC SULFIDES AND MONOCYCLIC AROMATIC HYDROCARBONS. THE DATA OBTAINED ALLOWED AN EXTRACTIVE SOLVENT (PHENOL) TO BE CHOSEN FOR SEPARATING THE CYCLIC SULFIDES FROM THE KEROSENE-GAS-OIL FRACTIONS. WITH THE STRAIGNT-RUN PETROLEUM FRACTION 275-350 DEGREES THE POSSIBILITY OF OBTAINING THE SULFIDE CONCENTRATES WITH THE HELP OF LIQUID EXTRACTION WAS EXPERIMENTALLY CONFIRMED. (HOLOMAN-BATTELLE)

Abstract  MIXTURES OF HYDROCARBONS, ALCOHOLS, ORGANIC ACIDS, AMINES, AND OTHER ORGANIC COMPOUNDS CAN BE SEPARATED WITHOUT ANY MARKED TAILING BY USING STEAM AS THE CARRIER GAS FOR GAS-SOLID CHROMATOGRAPHY. ACTIVATED ALUMINA SERVES AS A GOOD ADSORBENT FOR LOW-BOILING HYDROCARBONS, CHROMOSORB P FOR HIGH-BOILING HYDROCARBONS, DIATOMACEOUS FIREBRICK POWDER MODIFIED BY HYDROFLUORIC ACID FOR ALCOHOLS, KETONES, AND ESTERS, DIATOMACEOUS FIREBRICK POWDER CONTAINING LITTLE PHOSPHORIC ACID FOR CARBOXYLIC ACIDS AND PHENOLS, AND SINTERED MAGNESIA FOR AMINES. USE OF STEAM AS CARRIER GAS MAY CONSIDERABLY EXTEND THE APPLICABILITY OF GAS-SOLID CHROMATOGRAPHY. HIGH-BOILING MATERIALS, IN GENERAL, CAN BE ELUTED RATHER FAST WITH STEAM. WATER-CONTAINING SAMPLES CAN ALSO BE SUBJECTED TO THE ANALYSIS WITHOUT ANY DIFFICULTY. FOR EXAMPLE, EVEN THE SEPARATION OF 0.1 PPM C2-C7 FATTY ACIDS IN AQUEOUS SOLUTION CAN BE ACHIEVED IN THIS WAY. (MACKAN-BATTELLE)

Abstract  In the scope of investigating new solvents as potential replacements for chlorocarbons or aromatic hydrocarbons for separation of carboxylic acids from dilute aqueous solution, we have focused on the dibasic esters, which have perfect properties for industrial applications. For this purpose, liquid-liquid equilibrium data for water+formic acid+solvent (diethyl carbonate or diethyl malonate or diethyl fumarate) ternary systems were investigated at 298.15K and atmospheric pressure. The equilibrium results consisted of solubility data and tie-lines were presented in ternary phase diagrams. The reliability of the experimental tie-lines was confirmed by using Othmer-Tobias correlation. The experimental tie-line data were correlated by UNIQUAC model, which gave satisfactory representation for the systems. It is concluded that diethyl carbonate, diethyl malonate and diethyl fumarate may be adequate solvents to extract formic acid from its dilute aqueous solutions.

Abstract  The synthesis of racemic (S)-(+)- or (R)-(-)-[methyl-C-11]amphetamine (3) is reported. The alkylation of dimethyl 2-benzylmalonate with [C-11]methyl iodide yielded dimethyl 2-benzyl-2-([C-11]methyl)malonate (1) which was used as an intermediate in the synthesis of 3. Hydrolysis of 1 with NaOH and subsequent decarboxylation using glacial acetic acid and heating produced 2-benzyl-[3-C-11]propionic acid (2). Conversion of 2 into 3 was achieved via the intermediate isocyanate using diphenyl-phosphoryl azide (DPPA), and subsequently into the amine using conc. HCl. After purification by solid-phase extraction and preparative LC, (+/-)-3 was obtained with a radiochemical purity greater than 98 %. Starting with 3 GBq (81 mCi) [C-11]carbon dioxide, 145 MBq (3.9 mCi) (+/-)-[methyl-C-11]amphetamine was obtained in 45 min with a 22 % decay-corrected radiochemical yield. Enantiomerically pure 3 was obtained by the preparative LC separation of the (+)- or (-)-10-camphorsulfonamide derivatives of the racemate with a total decay-corrected radiochemical yield of 7 % (counted from the start of methyl iodide synthesis). In a typical synthesis, 27 MBq (0.7 mCi) enantiomerically pure (S)-(+)- or (R)-(-)-[methyl-C-11]amphetamine were obtained starting from 3 GBq (81 mCi) [C-11]carbon dioxide. The position of labelling was confirmed by a C-13 synthesis using the same reaction pathway, and analysis by C-13 NMR spectroscopy.

Abstract    Treatment of 6-methylsulfonyl-9-(2, 3, 5-tri-O-benzoyl-β-D-ribofuranosyl) purine with ethyl acetoacetate and sodium hydride in tetrahydrofuran afforded, after deblocking, 6-ethoxycarbonylmethyl-9-β-D-ribofuranosylpurine. Similarly, replacement of the 6-methylsulfonyl moiety with other carbanions derived from diethyl malonate, ethyl cyanoacetate, malononitrile, nitromethane, and sodium cyanide gave the corresponding 6-C-substituted purine nucleosides. Most of these derivatives exist as the 6-(1H)-exomethylene tautomeric forms. 6-Ethoxycarbonylmethylpurine riboside was further converted to 6-methyl, ethyl, propyl, butyl, and pentyl-purine ribosides by decarboxylation or prior alkylation of the methylene group followed by de-carboxylation. This reaction sequence facilitated the preparation of hitherto almost inaccessible alkyl or C-substituted purine nucleosides.

Abstract    The Michael addition of diethyl malonate to 1-acetyl-3-ethyl-2, 3-dihydro-6 (1H)-pyridone (3) in EtOH at 55° has been found to give the trans isomer (4a) and the cis isomer (4b) of diethyl 5-ethyl-2-oxo-4-piperidinemalonate in a ratio of 85 : 15. The stereochemical assignments were based on C-13 nuclear magnetic resonance spectroscopic evidence as well as chemical interrelation with substances of known configuration. The latter included decarbethoxylation of 4a and 4b in dimethyl sulfoxide-H2O-NaCl to give the lactam monoesters 5a and 5b, conversion of 4a into trans-1-benzyl-5-ethyl-2-oxo-4-piperidinemalonic acid (7a) through the lactim ether 9a and its benzylated product 8a, debenzylation of 7a with sodium in liquid ammonia to give 6a, and alkaline hydrolysis of 4a to 6a.

Abstract    Active methylene compounds, diethyl malonate, α-tetralone, dimedone, acetyl-acetone, malononitrile, and diketene, were reacted with 1-ethoxyisochroman (1) to give the corresponding 1-substituted isochroman derivatives, 4, 5, 6, 7, 8, 9, 10, and 11, respectively. When 4 was treated with sodium ethoxide or potassium tert-butoxide, ethyl 1, 4-dihydro-2-naphthoate (14a), ethyl 1, 2-dihydro-2-naphthoate (14b), and ethyl 2-naphthoate (13) were obtained. On the other hand, the reaction of 2-(1-isochromanyl) cyclohexanone (3) with potassium tert-butoxide afforded 9-formyl-1, 2, 3, 4-tetrahydroanthracene (20) and 1, 2, 3, 4, 9, 10-hexahydroanthracene (21). The conversion mechanisms of 1-substituted isochromans (2, 3, 4, and 7) into naphthalenes (13, 14a, b, and 18) and 1, 2, 3, 4-tetrahydroanthracenes (20 and 21) are proposed.

Abstract  The in vivo sex-linked recessive lethal test was carried out in Drosophila melanogaster to investigate whether or not five substituted 4-hydroxy-2H-chromen-2-ones can modulate the genotoxicity of the well-established mutagenic agent ethyl methanesulfonate (EMS). For this purpose, 3 days old Canton S males were treated with the potent mutagen EMS alone in concentration of 0.75 ppm, as well as in combination with one of the five 4-hydroxycoumarins, namely diethyl 2-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)malonate (2b), 3-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)pentane-2,4-dione (6b), 4-(4-(4-hydroxy-2-oxo-2H-chromen-3-yl)thiazol-2-ylamino) benzenesulfonic acid (4c), 4-hydroxy-3-(2-(2-nitropheny lamino)thiazol-4-yl)-2H-chromen-2-one (9c), and (E)-4-hydroxy-3-(1-(m-tolylimino)ethyl)-2H-chromen-2-one (5d), in concentration of 70 ppm. The frequency of germinative mutations increased significantly after the treatment with EMS and decreased after treatments with coumarins. The maximum reduction was observed after treatments with 2b, 6b, 4c, and 5d. By the formation of hydrogen bonds or electrostatic interactions with O(6) of DNA guanine, tested coumarins prevent EMS-induced alkylation. The results indicate a protective role of five 4-hydroxycoumarins under the action of a strong mutagen.

Abstract    Fischer indolization of ethyl pyruvate 5-chloro-2-methoxyphenylhydrazone (6) with anhydrous zinc chloride gave ethyl 4-amino-6-chloroindole-2-carboxylate (12) as a main product, with three other expected in doles, (7), (8) and (5). Cyclization of ethyl pyruvate 2-methoxyphenylhydrazone (1) with p-toluenesulfonic acid in the presence of diethyl malonate afforded ethyl 4-(ethoxycarbonylacetamido)-indole-2-carboxylate (28) and diethyl 4-(ethoxycarbonylacetamido)-3, 6'-biindole-2, 2'-dicarboxylate (30) with five other indole derivatives, (11), (10), (26), (27), and (32). The pathway leading to such a 4-aminoindole product in the abnormal Fischer indolization of a 2-methoxyphenylhydrazone derivative is discussed.