The Title Compound

The title compounds also undergo the Claisen rarrangement (5-allyloxypyrazoles 4-allyl-5-pyrazolones) and are readily transformed into 5-chloropyrazoles by means of phosphorus oxychloride (8OCHE1). In the presence of aluminum chloride 5-acyloxypyrazoles (481) undergo the Fries rearrangement affording 4-acyl-5-hydroxypyrazoles (482). 

Beyond the scope of this chapter, but similar in mode of formation and reactivity to the title compounds, are some three-membered rings with three heteroatoms. Oxadiaziridine... 

Within the constraints of this article it is impossible to be comprehensive in the coverage of the subject matter, in terms of the chemicals involved and in the widely varying practices and areas of the world in which the title compounds are ingested by farmed animals. This account is, however, intended to give an overview, citing some relevant examples, of the beneficial and adverse effects, in animals and on the environment, of man-made compounds and naturally produced compounds in extensive and commercial production systems. 

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

Both common and systematic names of compounds are used throughout this volume, depending on which the Editor-in-Chief felt was more appropriate The Chemical Abstracts indexing name for each title compound, if it differs from the title name, is given as a subtitle Systematic Chemical Abstracts nomenclature, used in both the 9th and 10th Collective Indexes for the title compound and a selection of other compounds mentioned in the procedure, is provided in an appendix at the end of each preparation. Registry numbers, which are useful in computer searching and identification, are also provided in these appendixes. Whenever two names are concurrently in use and one name is the correct Chemical Abstracts name, that name is adopted. For example, both diethyl ether and ethyl ether are normally used. Since ethyl ether is the established Chemical Abstracts name for the 8lh Collective Index, it has been used in this volume The 9th Collective Index name is 1,1 -oxybisethane, which the Editors consider too cumbersome. 

The compound known as 18-crown-6 is one of the simplest and most useful of the macrocyclic polyethers. Its synthesis in low yield was first reported by Pedersen. Greene and Dale and Kristiansen" have reported syntheses of the title compound from triethylene glycol and triethylene glycol di-p-toluenesulfonate. Both of these procedures use strong base and anhydrous conditions and achieve purification by more or leas classical methods. The combination of distillation and formation of the acetonitrile complex affords crown of high purity without lengthy chromatography or sublimation. ... 

The procedure described is essentially that of Belleau and Weinberg and represents the only known way of obtaining the title compound. One other quinone acetal, 1,4,9,12-t6traoxadispiro[4.2.4.2]tetradeea-6,13-diene, has been synthesized by a conventional method (reaction of 1,4-cyclohexanedione with ethylene glycol followed by bromination and dehydrobromination ) as well as by an electrochemical method (anodic oxidation of 2,2-(l,4-phenylenedioxy)diethanol ). Quinone acetals have been used as intermediates in the synthesis of 4,4-dimethoxy-2,5-cyclohexadienone,. syw-bishomoquinone, - and compounds related to natural products. ... 

Addition of bromine to the dienol acetate (49) gives the 6j5-bromo-A -3-ketone (50). Dehydrobromination of the crude bromo compound in DMF with lithium or calcium carbonate gives the title compound (51). ... 

The 7a-bromo-5a-6-ketone (56) is conveniently prepared from a mixture of the 5a- and 5j5-6-ketones (55) under equilibrating conditions. It is formed from the 5a-isomer (55) via the 5a-bromo-compound, and from the 5j -isomer (55) via the 7a-bromo-5i -6-ketone (see section II-A). Dehydrobromination is effected in DMF, and chromatography of the crude product separates the title compound (58) from remaining starting material and isomeric A -6-ketone (57). ... 

Acetoxyandrost-5-en-17-one (59) is converted into the ethylene ketal (60) by treatment with ethylene glycol, triethylorthoformate and p-toluenesulfonic acid. The ketal is brominated with pyridinium bromide perbromide in THF and then treated with sodium iodide to remove bromine from the 5 and 6 positions. This gives the 16a-bromo compound (61) which is hydrolyzed in methanol to the free alcohol (62). Dehydrobromination is effected with potassium Fbutoxide in DMSO to give the -compound (63). Acid catalyzed hydrolysis of the ketal in aqueous acetone gives the title compound (64). ... 

A solution of cholest-4-en-3-one (139), 1 g, in diethylene glycol dimethyl ether (20 ml) is treated for 1 hr with a large excess of diborane at room temperature under nitrogen and then left for a further 40 min. Acetic anhydride (10 ml) is added and the solution refluxed for 1 hr. The mixture is concentrated to a small volume, diluted with water and extracted with ether. The extracts are washed with 10% sodium hydroxide solution, then with water and dried over sodium sulfate. Removal of the solvent leaves a brown oil (1.06 g) which is purified by chromatography on alumina (activity I). Hexane elutes the title compound (141), 0.68 g mp 76-77°. Successive crystallization from acetone-methanol yields material mp 78-79°, [a]p 66°. 

To a mixture of naphthyloxazoline 71 (4.31 g, 12.97 mmol) in pyridine (4 mL) was added activated copper (1.99 g). The mixture was heated to reflux for 24 h then was cooled to rt, diluted with CH2CI2 and washed with aqueous ammonia until the copper had been completely removed. The organic phase was washed with water then dried over anhydrous magnesium sulfate, filtered, and concentrated to afford the title compound as a tan solid. This material was used without further purification. 

POCI3 was added to a solution of amide 62 (0.075g, 0.02 mmol) in toluene (5 mL). The reaction mixture was heated to 110 °C with stirring for 5 h, then cooled to rt. A solution of 2 N NaOH (10 mL) was added and the mixture was extracted with ether (3 x 15 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was then purified by flash chromatography on silica gel (40% Ethyl acetate/hexanes) to afford the 68 mg (95%) of the title compound as... 

Chlorobenzamidine (26) (15 g, 78 mmol), ethyl benzoylacetate (25) (20 g, 129 mmol), sodium carbonate (15 g, 141 mmol) and water (30 mL) were mixed and this mixture was brought to homogeneity by adding ethanol. The solution which resulted was stirred at rt for 16 h. The thick mixture was diluted with water (50 mL) and the solid was collected and washed with ethanol. The crude product was crystallized from acetic acid which furnished 9g of the title compound 27 (30%). m.p. 305-307°C. ... 

In general, all of the title compounds can be classified as either compounds in which the heteroarylium moiety remains in the molecule after the nucleophilic substitution (pathway a, formation of 45) or compounds in which that moiety was substituted by a suitable nucleophile to yield 46 (pathway b). Proper selection of the nucleophile Nu in 45 (or Nu in 46) should thus allow control of the consecutive substitution reactions, which would lead to a preference of 47 over 48 or vice versa (Scheme 14). 

Absorption and emission spectra of six 2-substituted imidazo[4,5-/]quinolines (R = H, Me, CH2Ph, Ph, 2-Py, R = H CH2Ph, R = Ph) were studied in various solvents. These studies revealed a solvent-independent, substituent-dependent character of the title compounds. They also exhibited bathochromic shifts in acidic and basic solutions. The phenyl group in the 2-position is in complete conjugation with the imidazoquinoline moiety. The fluorescence spectra of the compounds exhibited a solvent dependency, and, on changing to polar solvents, bathochromic shifts occur. Anomalous bathochromic shifts in water, acidic solution, and a new emission band in methanol are attributed to the protonated imidazoquinoline in the excited state. Basic solutions quench fluorescence (87IJC187). 

Meanwhile a stirred suspension of phosphorus pentachloride (14.99 g, 0.072 mol) in dry di-chloromethane (150 ml) was cooled to 0°C, and N,N-dimethylacetamide (27.5 ml) was added. The resulting solution was recooled to -10°C and 2-fur-2-yl)-2-methoxyiminoaceticacid (syn-isomer) (12.17 g, 0.072 mol) was added. The mixture was stirred at -10°C for 15 minutes and crushed ice (35 g) was added. The mixture was stirred at 0°C for 10 minutes, whereafter the lower dichloromethane phase was added over 10 minutes to the cephalosporin solution prepared above, cooled to -10°C so that the reaction temperature rose steadily to 0°C. The mixture was stirred at 0°C to 2°C for 1 hour, whereafter the cooling bath was removed and the reaction temperature allowed to rise to 20°C over 1 hour. The reaction mixture was then added slowly to 2 N hydrochloric acid (100 ml) diluted with cold water (1.15 C) at 5°C. The pH of the two-phase mixture was adjusted to below 2 with 2 N hydrochloric acid (10 ml), and the mixture was stirred and recooled to 5°C. The solid which precipitated was filtered, washed with dichloromethane (100 ml) and water (250 ml), and dried in vacuo at 40°C overnight to give the title compound (22.04 g, 86.6%). 

However the acid is prepared, the sodium salt may be prepared as described in U.S. Patent 3,503,967 Five liters of methylene chloride were added to a clean dry vessel equipped with stirrer. 7-[a(4-pyridylthio)acetamido] cephalosporanic acid (1,000 g) was added to the vessel, followed by 350 ml of triethylamine. The resultant solution was treated with decolorizing charcoal for 15 minutes and filtered. A solution of sodium-3-ethyl-hexanoate (27.3%) in butanol-methylene chloride was added to the filtrate with stirring. Seven thousand five hundred milliliters of acetone was added. Crystallization occurred while stirring was continued several hours under dry conditions. The crystals were collected by filtration, washed with large volumes of acetone, and then dried in vacuo at 50°C to yield about 950 g of the title compound. 

A solution of betamethasone 21-methanesulfonate (4 g) in dimethylformamide (25 ml) was treated with lithium chloride (4 g) and the mixture heated on the steam bath for 30 minutes. Dilution with water gave the crude product which was recrystallized to afford the title compound, MP 226°C. 

To which a solution of manganese sulfate (15 g), 3.1 g of chromium trioxide, 72 ml of water and 3.5 ml of sulfuric acid was added. After stirring for 3.5 hours at 3°C, extracted with diethyl ether. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate-benzene (1 1) as eluent to give 2.35 g of the title compound. 

Preparation of Intermediate Compound 2-Methyl-3-o-Tolyl-6-Sulfamyl-7-Chloro-4(3H)-Quinazoiinone Set up a 5-liter 3-necked flask fitted with a stirrer, condenser and a drying tube. To a stirred mixture of 100 g (0.342 mol) of powdered 4-chloro-5-sulfamyl-N-acetylanthranilic acid, 40.2 g (0.376 mol) of o-toluidine and 2.0 liters of dry toluene was added dropwise, over a period of 15 minutes, 21.7 ml (34.1 g) (0.248 mol) of phosphorus trichloride. The mixture was then refluxed for 10 hours. The solid turned somewhat gummy towards the latter part of the first hour. The mixture then became more free flowing as heating was continued. Let stand overnight. The yellow solid was filtered, washed with toluene and dried. The toluene filtrate was discarded. The dried solid was triturated with 1.5 liters of 10% sodium bicarbonate, filtered and the cake washed with water. The filtrate on acidification yielded 11.5 g of the starting acid. The damp product was dissolved in 4,5 liters of 95% ethanol and the solution treated with charcoal and filtered. On cooling filtrate yielded 69.5 g (55.5%) of the title compound, MP 271.5° to 274°C. 

For the condensation of the title compounds to give 1,3-dinitrodibenz[6,/]oxepins, see Houben-Weyl, Vol.6/4, p458. 

A mixture Df 3,7,8,12-tetraelhyl-2,13-dimethyltripyrrane-l, 14-dicarboxylic acid (1 e, 1 equiv), and 3,4-di-ethylpyrrole-2,5-dicarbaldehyde (2e, t equiv) was dissolved in 5% TFA/CH2C12 and stirred at rt for 2 h. The mixture was neutralized with Et3N and further reacted with DDQ (1 equiv) for 1 h. Column chromatography (neutral alumina) and recrystallization (CHCl3/MeOH) gave the title compound yield 60%. 

A mixture of 2,3.7,8.12,13.17.18-octaethylporphyrin (1. M = H2 500 mg. 0.94 mmol), anhyd K2CO, (3.8 g. 27 mmol) and freshly distilled 3-methylpyridine (25 inL) was refluxed under N2 and a solution of p-lol-uenesulfonylhydrazide (5.0 g. 27 mmol) in 3-mcthylpyridine (15 mL) was added dropwise over a period of 2.5 h. The mixture was refluxed for a further 2 h, cooled and extracted with benzene, which was washed with cold dil HC1 and extracted with 85% H3P04 (3 x 35 mL). The combined aqueous extracts were diluted to 60 % H3P04 (by addition of 40 mL of H20) and extracted with benzene. The benzene extracts were then washed with 60% H2P04 and H20 and evaporated to dryness. Crystallization (CHCI, /MeOH) gave the title compound yield 56 mg (11 %). 

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