Ring Contraction Products Research Articles

Photochemical oxidation of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (Emorfazone) by pyrimido[5,4-g]pteridine 5-oxide. An attempt to apply a functional chemical model for biological oxidations to drug-metabolism studies.

Irradiation of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (2) (Emorfazone) with ultraviolet (UV)-visible light in the presence of 1, 3, 7, 9-tetrabutyl-2, 4, 6, 8(1H, 3H, 7H, 9H)-pyrimido-[5, 4-g]pteridinetetrone 5-oxide (1a), followed by chromatography of the reaction mixture, resulted in the isolation of 5-(2, 3-dihydro-1, 4-oxazin-4-yl)-4-ethoxy-2-methyl-3(2H)-pyridazinone (3), 4-ethoxy-5-(2-hydroxyethylamino)-2-methyl-3(2H)-pyridazinone (4), 4-ethoxycarbonyl-2-methyl-4-morpholino-3(2H)-pyrazolone (5), 4, 4'-bi[4-ethoxycarbonyl-2-methyl-3(2H)-pyrazolone] (6) and 1, 3, 7, 9-tetrabutyl-2, 4, 6, 8(1H, 3H, 7H, 9H)-pyrimido[5, 4-g]pteridinetetrone (1b). The product 3 is produced as a result of photochemical dehydrogenation of 2 by 1a. The formation of the morpholine-ring-opening product 4, one of the metabolites of 2, was proved to occur via the autoxidation of 3 and subsequent stepwise ring cleavage in the presence of oxygen and moisture. The formation of the novel ring-contracted product 5 involves oxygen-atom transfer from 1a to 2 in an excited state. The dimer 6 was shown to be a secondary product formed by further photolysis of 5.

Syntheses and reactions of 9-substituted 10-phenylthioxanthenium salts: negative evidence for thia-anthracene oligomerisation

Various 9-aryl-10-phenylthioxanthenium salts have been prepared and their stereochemistry determined by 1H n.m.r. spectroscopy. Reactions of the 10-phenylthioxanthenium salts or 10-phenyl-10-thia-anthracenes with aryl-lithiums have been studied in order to investigate whether or not 10-thia-anthracenes cause oligomerisation. The 10-phenylthioxanthenium salts reacted with aryl-lithiums to give 9-phenylthioxanthenes in good yields. However, 10-phenylthioxanthenium salt (19) when treated with phenyl-lithium at –15 to –20 °C gave 9-phenylthioxanthenol (38)(17%) together with 9-phenylthioxanthene (13) because of the lability of 10-phenyl-10-this-anthracene to air. 10-Phenyl-9-(p-tolyl)-10-thia-anthracene (50) generated in situ from the sulphonium salt (22) and lithium di-isopropylamide failed to react with p-tolyl-lithium. An isolable ylide, 9-benzoyl-10-phenyl-10-thia-anthracene (52) was treated with p-tolyl-lithium at 0 °C to give 9-benzoylthioxanthene (4)(82%). In contrast, 9,9,10-triphenylthioxanthenium salt (24) on treatment with phenyl-lithium gave a ring-opened product (40), a ring-contracted product (41), diphenyl sulphide (42), and 9,9-diphenylthioxanthene (12). These results indicate that the 10-phenyl-10-this-anthracenes or the σ-sulphuranes of thioxanthenes do not cause oligomerisation.

Lewis Acid-Promoted Favorskii-Type Ring Contraction of Some Cyclic α-Bromo Ketones and Their Acetals

The α-bromo cycloalkyl aryl ketones 2a-d on heating with zinc chloride in methanol furnished in moderate to good yields the ring-contracted products 3a-d having gem methyl carbomethoxy function. The acetals of the related α-bromo ketones 7a-c, lacking the methyl group on the halogen-bearing carbon atom, afforded in acceptable yields the ring-contracted esters 8a-c when heated in protic solvent. The limitation of the present ring-contraction procedure has been discussed.

Cytochrome P-450-catalyzed rearrangement of a peroxyquinol derived from butylated hydroxytoluene. Involvement of radical and cationic intermediates.

The p-peroxyquinol derived from butylated hydroxytoluene, 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone, was degraded by the ferric form of rat liver cytochrome P-450, and the resulting products and their mechanisms of formation were investigated. Quinoxy radical BO. from homolysis of the O-O bond reacted by competing pathways; beta-scission yielded 2,6-di-t-butyl-p-benzoquinone, and rearrangement with ring-expansion produced an oxacycloheptadienone free radical (X(.)). This rearranged radical was stabilized by the captodative effect that facilitated competitive interactions with the P-450 iron-oxo complexes formed during O-O bond scission. Approximately 15% of X(.) was captured by oxygen rebound with a hydroxyl radical from the P-450 complex (FeOH)3+ to form a hemiketal, that led to the ring-contracted product 2,5-di-t-butyl-5-(2'-oxopropyl)-4-oxa-2-cyclopentenone by spontaneous rearrangement. The major fraction of X(.), however, underwent electron transfer oxidation to form the corresponding cation. Hydration of this cation produced the ring-contracted product, and proton elimination (or, alternatively, direct H(.) removal from X(.) led to the product 2,7-di-t-butyl-4-methylene-5-oxacyclohepta-2,6-dienone. The findings indicate that cytochrome P-450 intermediate complexes are mainly responsible for oxidation of X(.). The results complement our previous study with 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone (Thompson, J. A., and Wand, M. D. (1985) J. Biol. Chem. 260, 10637-10644), demonstrating competitive heterolytic and homolytic mechanisms of O-O bond cleavage, and competitive rebound and oxidation processes when a substrate-derived radical interacts with P-450 complexes.

ChemInform Abstract: 5‐Thiopyranoses. Part 8. Sulphur Participation in Displacement Reactions of Sulphonate Esters of S‐Thio‐D‐ribose and S‐Thio‐D‐xylose Derivatives.

AbstractThe 4‐mesyl group of the thiopyranose (I) is displaced by intramolecular attack by sulphur leading to a cyclic episulphonium ion which in turn reacts with nucleophiles to give ring contracted products of type (II) and (III).

Base induced skeletal rearrangements via spirocyclic ipso intermediates in dibenzodithiocinium salts

Treatment of 6-methyl-12-oxo-5H,7H-dibenzo[b,g] [1,5]-dithiociniumsalt ( 1a ) with methanolic KOH afforded the ring contracted product ( 2a ), i. e., thiepin derivatives, trans- 2a . (44%) and cis-2a (19%). However, the corresponding deoxodithiociniumsalt ( 1b ) gave an unexpected isomer ( 2b ) with the same thiepin skeleton. These are explained by tandem sigmatropy.

Ring contraction of 2-chlorocyclohexanone with Grignard reagents.

The reaction of 2-chlorocyclohexanone with phenylmagnesium bromide in refluxing tetrahydrofuran unexpectedly afforded the ring-contracted product, cyclopentyl phenyl ketone, as the main product in moderate yield. The reactivities of several cyclic 2-haloketones were examined.

Ring contraction and dehydrogenation in polycyclic hydroaromatics at coal liquefaction temperatures

The thermal behaviour of 1,2,3,4,5,6,7,8-octahydroanthracene and 1,2,3,4,5,6,7,8,9,10,11,12-dodecahydrotriphenylene has been observed over the temperature range 400–500 °C in the presence and absence of bituminous coal. It is shown that the ratio of ring contracted product to dehydrogenated product increases with increasing reaction temperature, but the amount of ring dehydrogenated product is increased considerably by the presence of coal. The decomposition reactions are similar to those reported for tetralin, except that the polycyclic hydroaromatics react at much lower temperatures, and also further degrade by ring cracking reactions.

ChemInform Abstract: A NEW RING TRANSFORMATION OF 3,4‐DIHYDRO‐1‐METHYL‐6‐PHENYL‐1,4,5‐BENZOTRIAZOCIN‐2(1H)‐ONES INTO 1‐(METHYLCARBAMOYL)METHYL‐3‐PHENYL‐1H‐INDAZOLES

3, 4-Dihydro-1-methyl-6-phenyl-1, 4, 5-benzotriazocin-2 (1H)-one (1a) readily undergoes a transformation into 1-(methylcarbamoyl) methyl-3-phenyl-1H-indazole (3a) when its chloroform solution is kept at room temperature. The 8-chloro, 8-bromo and 8-fluoro derivatives of 1a (1b, 1c and 1d) similarly afford the corresponding 5-halogenoindazoles (3b, 3c and 3d), but 3, 4-dihydro-6-phenyl-1, 4, 5-benzotriazocin-2 (1H)-one, and its 1-benzyl and 1-dialkylaminoalkyl derivatives give no ring contraction product under the same conditions.

ChemInform Abstract: SELECTIVE BROMINATIVE CYCLIZATION OF POLYENES ASSISTED BY ACETONITRILE. APPLICATION TO THE SYNTHESIS OF ACORATRIENE

AbstractDie Diene (I) reagieren mit dem Tetrabromid (II) und Acetonitril zu den Zwischenstufen (III), die zu den Cyclohexenen (IV) gespalten werden; mit Wasser entstehen die Amide (VI) und (VII).

Formation, dealkylation, and nucleophilic substitution of some mono- and di-alkoxypyridoazepines

The photo-induced ring-expansions of 5-azido-, 8-azido-, 6-azido-8-methoxy, and 8-azido-6-methoxy-quinolines to alkoxypyridoazepines in alcohol–alkoxide–dioxane solution containing 18-crown-6 are reported, although in some instances azepinone and/or azepine ring-contraction products are noted. In addition, ring-expansions in the presence of phenoxide ion have been achieved for the first time. 1H N.m.r. spectra indicate that some of the pyrido-azepines and -azepinones are formed as mixtures of the 5H- and 7H-isomers.

THE REACTION OF 2H-THIIN DERIVATIVES WITH PERACID. RING CONTRACTION AND ALKOXYLATION REACTIONS

Abstract The cycloaddition reaction of aromatic thioketones (aryl naphthyl thioketones and 2-benzofuryl phenyl thioketone) with 2-chloroacrylonitrile followed by elimination of hydrogen chloride gave some 2H-thiin derivatives. The products reacted with MCPBA and an alcohol to afford ring-contracted product and alkoxylated derivatives.

Versuche zur Oxidation von 1.5-Benzothiazepin — bzw. 1.5-Benzoxazepin- 2.4-3H.5H-dionen / Investigations Concerning Oxidation Reactions of 1,5-Benzthiazepin — and 1,5-Benzoxazepin- 2,4-3H,5H -diones

Attempts to oxidize the 1,5-benzothiazepin-2,4-3H,5H-dione (1) using NaNO2/Acetic acid lead to isolation of two ring contracted products, namely the 1,4-benzthiazin-derivatives 4 and 5. A reasonable reaction pathway concerning the formation of these compounds is discussed. A simple synthesis of 6-methyI-1,5-benzoxazepin-2,4-3H,5H-dione (13) is described, the transformation of which into the corresponding vic. trione fails, even using a great number of oxidizing procedures. In some cases so far unknown malonic acid derivatives 14, 15 and 16 can be obtained.

Reactions on methyl 2-deoxy-2-trifluoroacetamido-3- O-trifluoromethylsulfonyl-α- d-glucopyranoside derivatives: formation of ring-contraction compounds

The behavior of methyl 4,6- O-cyclohexylidene-2-deoxy-2-trifluoroacetamido-3- O-trifluoromethylsulfonyl-α- d-glucopyranoside ( 6) with several reagents was examined. By reaction of 6 with lithium chloride or sodium iodide in N,N-dimethylformamide, the corresponding 3-chloro-3-deoxy- and 3-deoxy-3-iodo-allopyranosides were readily obtained. Treatment of 6 with sodium benzoate in N,N-dimethylformamide, or sodium methoxide in methanol, gave several products derived from an initially formed 2,3- allo-epimine. The difference in the foregoing reactions is explained on the basis of hydrogen bonding between 2-N HCOCF 3 and 1- OMe. Solvolysis of 6 and methyl 6-benzyloxycarbonylamino-2,6-dideoxy-2-trifluoroacetamido-3- O-trifluoromethylsulfonyl-α- d- glucopyranoside ( 26) in hot (100°) methanol gave ring-contraction products ( 18, 27) having bicyclic d-xylofuranoside structures.

Selective brominative cyclization of polyenes assisted by acetonitrile. Application to the synthesis of acoratriene

Reaction of polyenes (4a, b) with 2,4,4,6-tetrabromocyclohexa-2,5-dienone at –20 °C in the presence of MeCN and subsequent quenching with water gives monocyclic amides (8a, b) and (9a, b), while the cycloalkene (7a, b) was formed during the reaction at room temperature; acoratriene (12) was elaborated from (7b)via a ring contraction product (10b).

A new ring transformation of 3,4-dihydro-1-methyl-6-phenyl-1,4,5-benzotriazocin-2(1H)-ones into 1-(methylcarbamoyl)methyl-3-phenyl-1H-indazoles.

3, 4-Dihydro-1-methyl-6-phenyl-1, 4, 5-benzotriazocin-2 (1H)-one (1a) readily undergoes a transformation into 1-(methylcarbamoyl) methyl-3-phenyl-1H-indazole (3a) when its chloroform solution is kept at room temperature. The 8-chloro, 8-bromo and 8-fluoro derivatives of 1a (1b, 1c and 1d) similarly afford the corresponding 5-halogenoindazoles (3b, 3c and 3d), but 3, 4-dihydro-6-phenyl-1, 4, 5-benzotriazocin-2 (1H)-one, and its 1-benzyl and 1-dialkylaminoalkyl derivatives give no ring contraction product under the same conditions.

The photolysis of η 6- o-, m-OR P-azidotoluene-η 5-cyclopentadienyliron hexafluorophosphate

Photolysis studies were carried out using dilute solutions of η 6- o-, m- or p-azidotoluene-η5 -cyclopentadienyliron hexafluorophosphate (I, II or III, respectively) in cyclohexane or CH 2Cl 2 as solvent. From I, the only ring contraction product was 1-cyano-2-methylferrocene (IV) while the analogous product from III was 1-cyano-3-methylferrocene (V). With II as substrate, a 1:3 mixture of IV and V was obtained. When the solvent was CH 2Cl 2, some ferrocene was also formed. Mechanistic interpretations of these results are discussed.

On the amination of 1,2,4‐triazines by potassium amide in liquid ammonia and by phenyl phosphorodiamidate. A 15n‐study

AbstractThe amination of 5‐R‐ and 6‐R‐3‐X‐1,2,4‐triazines (R = C6H5, t‐C4H9, X = SCH3, SO2CH3, N+ (CH3)3, Cl) by potassium amide in liquid ammonia has been studied. In all reactions the formation of the corresponding 3‐amino‐1,2,4‐triazines takes place; in some reactions by‐products were found: from 5‐phenyl‐ and 5‐t‐butyl‐3‐(methylthio)‐1,2,4‐triazine a ring contracted product i.e. 5‐phenyl and 5‐t‐butyl‐3‐(methylthio)‐1,2,4‐triazole, from 6‐phenyl‐3‐(methylthio)‐1,2,4‐triazine the dimer 3,3′‐bis‐(methylthio)‐6,6′‐bisphenyl‐5,5′‐bi‐1,2,4‐triazine and from 5‐t‐butyl‐3‐(trimethylammonio)‐1,2,4‐triazine chloride compound bis‐(5‐t‐butyl‐1,2,4‐triazin‐3‐yl)‐ amine. Furthermore the conversion of 5‐phenyl‐ and 5‐t‐butyl‐1,2,4‐triazin‐3‐one into the corresponding 3‐amino compound by treatment with phenyl phosphorodiamidate (PPDA) was studied. A 15N study of these aminations showed that nearly all compounds undergo substitution according to both SN(AE) and SN(ANRORC) processes. The contribution of each of the competitive mechanisms to the amination is strongly influenced by the character of the leaving group.

ChemInform Abstract: CYCLOPENTANOIDS FROM PHENOL. VI. CHIRAL PROSTANOID INTERMEDIATES

AbstractAus Phenol oder 2,4,6‐Trichlorphenol werden nach bekannten Verfahren die racemischen Säuren (50‐60% Ausb.) (i)‐(Ia) und (i)‐(Ib) erhalten und über die (‐)‐Brucinsalze (74%) in die enantiomeren Säuren (‐)‐(Ia) (94%) bzw. (+)‐(Ib) (99%) gespalten, die oxidativ zu den Cyclopentenonen (IIa) (100%) bzw. (IIb) (98%) decarboxyliert werden.

The thermolysis and photolysis of η 6-azidobenzene-η 5-cyclopentadienyliron hexafluorophosphate

η 6-Azidobenzene-η 5-cyclopentadienyliron hexafluorophosphate (I) was synthesized and its thermolysis and photolysis under different experimental conditions were studied. Both reactions gave rise to various amounts of a ring contraction product, cyanoferrocene, and in most cases some η 6-aniline-η 5-cyclopentadienyliron hexafluorophosphate. The formation of these products may be explained as arising from the phenylnitrene complex as a reaction intermediate. The contrast in behaviors of the uncomplexed phenylnitrene and the complexed nitrene from I is also discussed.