2-Acyloxyacetylthiophenes

Abstract

Vol. 71 g., m. p. 190-213°, was recrystallized three times from dioxane yielding a product that melts at 248.5°. Substituted 2-N4-Acetylsulfanilamidoquinoxalines The amines were dissolved or suspended in pyridine and ^-acetylaminobenzenesulfonyl chloride added while the mixture was stirred, 2 -N4-Acetylsulfanilamido -5 (or 8)-chloroqulnoxaline.-To a mixture of 11.7 g. of the amine in 60 ml. of dry pyridine was added 16.7 g. of ^-acetylaminobenzene sulfonyl chloride in four portions at ten-minute intervals, During the addition, the mixture warmed up to 35°. After being stirred for one hour, the resultant clear yellow solution was heated on a water-bath at 650 for one-half hour. The mixture was then poured into 800 ml. of hot water and the product, which crystallized when the mixture was stirred, was filtered and air dried. The crude product, 20.0 g., was dissolved in 250 ml. of 1.3 N sodium hydroxide and filtered; 4.45 g. of insoluble material, m. p. 208-210°, was obtained. The filtrate was acidified with glacial acetic acid yielding light yellow amorphous material, m. p. 245-252°( 14.7 g., 62% yield). The analytical sample was crystallized from glacial acetic acid, m. p. 252-255°.2-N4-Acetylsulfanilamido-6(or 7) -carboxamidoquinoxaline.-A mixture of 1.08 g. of 2-chloro-6(or 7)-carbamidoquinoxaline, 1.07 g. of acetylsulfanilamide, 0.65 g. of potassium carbonate and 50 mg. of copper powder in a Pyrex test-tube was stirred and heated at 180-190°in an oil-bath for fifteen minutes. The dark mixture was extracted with 10 cc. of 10% sodium hydroxide, filtered from the chi oro compound that had not reacted and precipitated by acidification with dilute acetic acid. The oil that separated solidified on trituration with isopropyl alcohol. Recrystallization from glacial acetic acid yielded product, m. p. 277°about 500 mg. SulfonamidesThe acetyl derivatives were hydrolyzed by boiling with aqueous sodium hydroxide or ethanolic hydrogen chloride. 2-Sulfanilamido-5(or 8)-chloroqumoxaline.-A solution of 11.95 g. of the acetyl compound in 75 ml. of 2.5 Nsodium hydroxide was heated for one-half hour on a steam-bath. The crude product, 10.25 g., 97% yield, was precipitated by neutralization with acetic acid. The crude product, m. p. 210-213°, was purified in 87% recovery by dissolving in hot 5 N ammonium hydroxide, treating with charcoal and precipitating with acetic acid, m. p. 213-215°.

Facile Synthesis of Heterocycles via 2-Picolinium Bromide and Antimicrobial Activities of the Products

“…The required starting material 2-bromoacetylthiophene ( 1 ) was prepared as previously described [ 4 ]. Treatment of 1 with 2-picoline ( 2 ) in refluxing dry THF afforded the 2-picolinium salt 3 in 80% yield ( Scheme 1 ).…”

“…Elemental analyses were carried out by the Microanalytical Center of Cairo University, Giza, Egypt. The starting materials 2-bromoacetylthiophene ( 1 ) [ 4 ], N -phenylmaleimide ( 5 ) [ 20 ], ethyl (4-chlorophenylmethylene)cyanoacetate 9c , benzylidene acetophenone and 2-substituted 3-aryl-or heteroarylprop-2-ene nitriles 16 and 14 , were prepared as previously reported in the literature [ 21 ].…”

“…Many thiophene derivatives have been reported to exhibit interesting pharmaceutical properties, including antimicrobial [ 1 ], anticancer [ 2 ], anti-inflammatory [ 3 ], bacteriostatic and fungistatic activity [ 4 ]. Some other derivatives exhibit strong inhibition of NHE-1 and cardioprotective efficacy [ 5 ].…”

Synthesis and Characterization of Mixed Oligoheterocycles Based on End-capped Oligothiophenes

“…[17] Synthesis: The central building block for the synthesis of all five novel mixed oligoheterocycles 2 ± 6 is 2- (4,5,6,7-tetrahydrobenzo[b]thien-2-yl)thiophene (9). Bithiophene 9 is available from the ring-closure reaction of 1,4-diketone 8, which was synthesized from a-halogenoketone 7 [18] and 1-(N-pyrrolidino)cyclohexene in 43 % yield. Reaction of 1,4-diketone 8 with either diphosphorus pentasulfide or Lawessons reagent (L.R.)…”

“…After evaporation of the solvent, the remaining residue was purified by chromatography (SiO 2 /toluene) to yield 16 as a yellow solid (6.88 g, 51 % 25.4, 25.2, 23.3, 22.6 (C1,2,3,4); C 14 H 13 ClOS 2 (296.8): calcd C 56.65,H 4.42,S 21.60;found C 56.84,H 4.18,5,6,thien-2-yl)-2-(aminoacetyl)thiophene hydrochloride (17): Compound 16 (2.32 g,7.82 mmol), hexamethylenetetraamine (1.10 g, 7.82 mmol), and sodium iodide (1.17 g, 7.82 mmol) were suspended in ethanol and stirred for one week at room temperature. Concentrated hydrochloric acid (3 mL) was added and the mixture was warmed to 50 8C and then stirred for additional 5 h. The precipitated crude hydrochloride was isolated by filtration and recrystallized twice from ethanol to yield 17 as an ochre powder (1.50 25.2, 24.8, 23.1, 22.4 (C1,2,3,4); C 14 H 16 ClNOS 2 (313.87): calcd C 53.57, H 5.14,N 4.46,S 20.43;found C 53.44,H 5.18,N 4.44,5,6,thien-2-yl)thiophene-2-carbonic acid (18): nBuLi (2.86 mL of a 1.6 m solution in hexane, 4.58 mmol) was added to a stirred solution of 9 (1.00 g, 4.54 mmol) in dry diethyl ether (25 mL) was slowly added and the mixture then cooled to À 50 8C. Gaseous carbon dioxide was bubbled through the mixture over a period of 1 h. The organic phase was hydrolyzed and extracted with additional water.…”