Synthesis and reactions of 3-aroyl derivatives of 4-hydroxy-2-quinolones and 4-hydroxycoumarin

3-Aroyl-4-hydroxy-2-quinolones 4 and 11 can be synthesized starting with 1 or 9 via Fries rearrangement of the corresponding esters 3 and 10 , catalyzed by potassium cyanide and 18-crown-6. A one pot procedure is presented in which the esters do not need to be isolated. Reduction of the aryl ketones 4 and 11 with zinc dust leads to the benzyl derivatives 5 and 12 . Reaction of the aryl ketones 4 and 11 with hydroxylamine and subsequent heating of the crude product leads via thermal Beckmann rearrangement and dehydration to oxazoloquinolones 7 and 14 . 2-Aroyloxypyrido[1,2-a]pyrimidin-4-ones 17 and 20 could not be converted to the corresponding ketones by Fries rearrangement.     

The rearrangement of 4-hydroxyeoumarin carbamates

Carbamate esters of 4-hydroxycoumarin were prepared, and their base-catalyzed and thermal rearrangement to 3-(N-substituted carbamoy])-4-hydroxycoumarins were studied. A mechanism for the rearrangement is proposed.     

Stabilization of even-electron ions by cyclization of substituents on 3N- and 4N-nitrogens in 4N-substituted cytosines

Electron impact mass spectra of 4N-substituted derivatives of cytosine are reported. The strong influence of 4N-substituents on the mode of mass fragmentation occurring upon electron impact ionization was proved. The presence of α-carbon in the 4N-substituent extends the possibilities of fragmentation via rearrangement leading to formation of even-electron bicyclic ions containing quaternary 3N-nitrogen. When β-carbon was present in the 4N-substituent, the decomposition based on elimination of alkenes was detected as well as the rearrangement leading to formation of bicyclic even-electron ions containing quaternary 3N- or 4N-nitrogen.     

Thermische Umwandlung von Penta-2, 4-dienyl-phenyläthern in 4-(Penta-2, 4-dienyl)-phenole; [5s, 5s]-sigmatropische Umlagerungen

trans-Penta-2, 4-dienyl phenyl ether (trans- 1 ), on heating at 186° in a five-fold excess of N, N-diethylaniline, gave via a [3s, 3s] rearrangement 23% of 2-(1-vinyl-allyl)-phenol ( 2 ) and via a [5s, 5s] rearrangement 37% of trans-4-(penta-2, 4-dienyl)-phenol (trans- 3 ). The dimeric residue was formed from trans- 1 by diene synthesis. By working at high dilution, the formation of dimeric products was kept to a minimum. The inversion of the migrating pentadienyl residue during the rearrangement of trans- 1 to trans- 3 was proved by rearrangement of the methyl labelled ether trans, trans- 4 to the p-dienyl-phenol 8 (93%) (accompanied by only 7% of 9 ). trans- 5 gave the p-phenol 9 quantitatively. cis-Penta-2, 4-dienyl phenyl ether (cis- 1 ) was converted to 10 on heating, by a fast [1, 5s] H-migration. The above mentioned reactions of the type trans- 1 → trans- 3 show first order kinetics and are the first examples of [5s, 5s] sigmatropic rearrangements shown to go through a ten-membered transition state. The conformation of the activated complex is discussed in the light of the stereochemistry of the migrating penta-2, 4-dienyl group.     

Competitive Photochemical Pathways in the Rearrangement of Tetrasubstituted 4H-Thiopyrans

Summary. The photoisomerization of 4,4-dialkyl-2,6-diphenyl-4H-thiopyrans and 4-benzyl-2,4,6-triphenyl-4H-thiopyran was investigated and compared with those of the 2,4,4,6-tetraaryl- and 4-alkyl-2,4,6-triaryl-4H-thiopyran analogues reported earlier. Obviously, the alkyl groups at the 4-positions of the 4H-thiopyrans strongly diminish the efficiency of the di--methane rearrangement and, contrastingly, a four-electron suprafacial [1,3]-sigmatropic rearrangement is found to be highly efficient.     

3-Hydroxy-4-nitro-cyclohexanone aus Ketonen und 4-Nitrobuttersäurechlorid. Eine ringerweiternde Fünfringanellierung

3-Hydroxy-4-nitro-cyclohexanones from Ketones and 4-Nitrobutanoyl Chloride. A Ring Enlarging Five-Ring Annulation The 6-nitro-1, 3-diketones 5, 8, 9, 10 , and 11 , prepared by a 1:1 acylation at the C-atom of non-hindered lithium enolates with 4-nitrobutanoyl chloride according to equation 3, are cyclized with sodium hydrogen carbonate in aqueous tetrahydrofuran to give the hydroxy-nitro-ketones 13–17 . Such cyclic nitroaldols are not formed from the cyclopentanone, -heptanone, and -octanone, nor from the aryl derivatives 4, 6, 7 and 12 , respectively. Except for the vicinally trisubstituted compound 14 , the cyclization products are isolated in diastereomerically pure form. A crystal structure X-ray analysis reveals the trans-decalone and the cisβ-nitroalcohol configurations of the product 13 from cyclohexanone (see Fig. 1–3). Acetalization to 21–25 and catalytic hydrogenation of the nitro groups furnishes the amino alcohols 27–31 (Table 4) which are substrates for the Tiffeneau-Demjanow rearrangement (see Schemes 2, 3, 4 and 5), From the stereoelectronic control of this sextett rearrangement we deduce the configurations of the 1, 4-diketones 35, 36, 39, 40, 43, 44, 46 , and 47 formed under kinetic or thermodynamic conditions. The six-ring annulation with nitrobutanoic acid and the subsequent rearrangement are shown in Scheme 6; the sequence of reactions described here allows to carry out a ring enlargement of a cyclic ketone by one C-atom, with simultaneous annulation of a cyclopentanone ring.     

Alkylations of N4‐(4‐Pyridyl)‐3,5‐di(2‐pyridyl)‐1,2,4‐triazole: First Observation of Room‐Temperature Rearrangement of an N4‐Substituted Triazole to the N1 Analogue

Attempts to use alkylation to introduce a positive charge at the nitrogen atom of the 4‐pyridyl ring in the bis(bidentate) triazole ligand N⁴‐(4‐pyridyl)‐3,5‐di(2‐pyridyl)‐1,2,4‐triazole ( pydpt ) were made to ascertain what effect a strongly electron‐withdrawing group would have on the magnetic properties of any subsequent iron(II) complexes. Alkylation of pydpt under relatively mild conditions led in some cases to unexpected rearrangement products. Specifically, when benzyl bromide is used as the alkylating agent, and the reaction is carried out in refluxing acetonitrile, the N⁴ substituent moves to the N¹ position. However, when the same reaction is performed in dichloromethane at room temperature, the rearrangement does not occur and the desired product containing an alkylated N⁴ substituent is obtained. Heating a pure sample of N⁴‐Bzpydpt?Br to reflux in MeCN resulted in clean conversion to N1Bzpydpt.Br . This is consistent with N4‐Bzpydpt.Br being the kinetic product whereas N1Bzpydpt.Br is the thermodynamic product. When methyl iodide is used as the alkylating agent, the N⁴ to N¹ rearrangement occurs even at room temperature, and at reflux pydpt is doubly alkylated. The observation of the lowest reported temperatures for an N⁴ to N¹ rearrangement is due to this particular rearrangement involving nucleophilic aromatic substitution: a possible mechanism for this transformation is suggested.     

Stereochemie des Übergangszustandes aliphatischer CLAISEN-Umlagerungen. Vorläufige Mitteilung

The stereochemistry of the transition state in the CLAISEN rearrangement of crotyl propenyl ethers ( 2 ) has been established. By heating trans, cis-, cis, cis- and trans, trans-crotyl propenyl ether at 142,5°, erythro and threo 2, 3-dimethylpent-4-en-1-al ( 3 and 4 ) were obtained. From the ratio 3/4 it was shown that the rearrangement of the three ethers largely involves (97–98%) a chair-like transition state.     

Rearrangement of 1,4-benzodiazepin-2,4-diones to 3,l-benzoxazin-4-ones

Treatment of 7-chloro-3,4-dihydro-1H-1,4-benzodiazepin-2,5-dione (Ia) with refluxing acetic anhydride in the presence of pyridine afforded 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one (IIa). A plausible reaction path for this novel rearrangement reaction is described: Ia → 4-acetyl-7-chloro-3,4-dihydro-lH-1,4-benzodiazepin-2,5-dione → 7-chloro-1,4-diacetyl-3,4-dihydro-lH-1,4-benzodiazepin-2,4-dione → IIa. When 7-chloro-3,4-dihydro-4-methyl-lH-1,4-benzodiazepin-2,5-dione (Ib), 3,4-dihydro-4-methyl-1H-1,4-benzodiazepin-2,5-dione (Id) and 3,4-dihydro-1-methyl-1H-1,4-benzodiazepin-2,5-dione (Ie) were allowed to react with acetic anhydride under conditions similar to those used for the rearrangement reaction, only acetylation occurred.     

Mass spectral rearrangements of 3-arylsulphonyl-2-arylthiopropenes and N-(4′-arylsulphonyl-2′-butynyl)-N-(4″-arylthio-2″-butynyl)anilines

Under electron impact the title compounds undergo skeletal rearrangement in addition to the anticipated modes of cleavage. The 3-arylsulphonyl-2-arylthiopropenes readily eliminate sulphur dioxide. Other modes of fragmentation include rearrangement to a bisaryl sulphide moiety and sulphone-sulphinate rearrangement. The formation of a bisaryl sulphide ion is analogous to the behaviour of the isomeric trans-1-arylsulphonyl-2-arylthiopropenes. N-(4′-Arylsulphonyl-2′-butynyl)-N-(4″-arylthio-2″-butynyl) anilines do not undergo any of the skeletal rearrangements mentioned above, but display the concerted loss of the arylsulphonyl and arylthio moieties. Similar eliminations have been observed from the analogous bis-sulphides and bis-sulphones.     

Säurekatalysierte Umlagerung von Allyl-cyclohexadienon-tosyl-hydrazonen: Beispiel einer Dienimin-Anilin-Umlagerung

The tosylhydrazones of 4-allyl- and 4-crotyl-4-methyl-cyclohexa-2, 5-dien-l-one ( 14 and 15 ) rearrange in the presence of acid to yield the corresponding 2-allyl- and 2-α-methylallyl-hydrazines 17 and 18 , respectively. A similar behaviour is shown by the tosylhydrazone of 2-allyl-2-methyl-cyclohexa-3, 5-dien-1-one ( 16 ). 16 could not be isolated. The observed acidcatalysed [3 s, 3 s]-sigmatropic rearrangement of the tosylhydrazones can be regarded as a rearrangement of the dienimine-aniline type.     

Facile rearrangement of 2-amino-3-carbethoxy-4-ethylfuro[3,2-b]pyridinium cation to 2-oxo-3-cyano-4-ethyl-4H-furo[3,2-b]pyridine

The rearrangement of 2-amino-3-carbethoxy-4-ethylfuro[3,2-b]pyridinium iodide in basic solution was studied. The reaction product is 2-oxo-3-cyano-4-ethyl-4H-furo[3,2-b]pyridine which was obtained also by alkylation with ethyl iodide and sodium hydride in dimethylformamide of 2-oxo-3-cyano-3H-furo[3,2-b]-pyridine or of p-nitrophenyl-3-acetoxypyridine-2-cyanacetate.     

Synthese von 4-halogensubstituierten Analogen von Trimethoprim

The Synthesis of 4-Halogen-substituted Analogs of Trimethoprim The four 2,4-diamino-5-(4-halo-3,5-dimethoxybenzyl)pyrimidines 20a-d have been synthesized along known routes, i.e. form the corresponding aldehydes 17a-d via the aminomethylidene-derivatives 18a-d and 19a-d , respectively (Scheme 4). All four aldehydes were prepared from a common intermediate, methyl 4-amino-3,5-dimethoxybenzoate ( 3 ), which was obtained from dimethyl 2,6-dimethoxyterephthalate ( 2 ) and hydroxylamine in a regioselective Lossen-type rearrangement mediated by polyphosphoric acid (Scheme 1). Under identical rearrangement conditions 2,6-diethoxyterephthalate ( 12 ) led, in addition to the amine 14 , to the benzoxazolone 15 (Scheme 2). Scope and mechanism of this reaction are discussed. - The antimicrobial activity of the diamino-pyrimidines 20a-d , expressed as the inhibition of E. coli-dihydrofolate reductase, has been measured and compared with that of trimethoprim ( 1 ), an established antimicrobial agent.     

Thermische Umlagerungen von halogensubstituierten Aryl-propargyläthern

7-Chloro-2-chloromethyl-benzofuran (13) and 3, 8-dichloro-2 H-1-benzopyran (12) are the main products from the thermal rearrangement (230–260°) of 2, 6-dichlorophenyl propargyl ether (7) . Compounds 17 , 18 and 19 are also formed, but in much smaller amounts (scheme 2 and table 1). However, in the case of the bromo-compounds 8 and 9 the rearrangement products are the benzofuran derivatives 21 and 22 , containing one bromine atom less per molecule (scheme 4). The corresponding naphthyl propargyl ethers 10 and 11 can be rearranged much more easily (180°) to the halogeno-naphthofurans 24 and 26 respectively. In the case of the bromo-ether 11 , 2-methyl-naphtho[2, 1-b]furan (25) is also formed (scheme 5). If the propargylic hydrogen atoms in 7 and 11 are replaced by deuterium atoms, then after rearrangement the deuterium atoms in the products d- 13 and d- 26 are found in the β-positions to the oxygen atom of the furan ring (schemes 3 and 5). It is suggested that initially a [3s, 3s]-sigmatropic rearrangement of the aryl propargyl ethers to the 6-allenyl-6-halogeno-cyclohexa-2, 4-dien-1-ones (e.g. a ) occurs and that from these the isolated products are formed via radical pathways (scheme 6). Under neutral conditions aryl propargyl ethers containing a free ortho-position give on heating benzopyran derivatives [2]. When this thermal reaction is carried out in sulfolane in the presence of powdered potassium carbonate, 2-methyl-benzofuran derivatives are formed (table 2). This leads to the possibility of preparing, depending on the conditions, either benzopyran or benzofuran derivatives by the Claisen rearrangement of aryl propargyl ethers. The mechanism for the formation of the benzofurans is given in scheme 9.     

Heterocyclic Rearrangement of 4,5,6,7-Tetrahydro-6,6-dimethyl-benzo[c][1,2,5]oxadiazol-4-one (Z)-Arylhydrazones into Corresponding 2-Aryl-4,5,6,7-tetrahydro-2H-benzo[d][1,2,3]triazol-4-one Oximes

The thermal base-catalysed and photochemical transformation (Boulton-Katritzky rearrangement) of the title tetrahydrobenzo[c][1,2,5]oxadiazoles to tetrahydro-2H-benzo[d][1,2,3]triazoles is studied. Attempts to induce analogous rearrangement in tetrahydro-2H-benzo[d][1,2,3]triazol-4-one arylhydrazones or oximes failed. Some CNDO/2 calculation are also carried out.     

The chemistry of 4-hydrazino-7-phenylpyrazolo[1,5-a] -1,3,5-triazines

The reaction of 4-hydrazino-7-phenylpyrazolo[1,5-a]-1,3,5-triazine ( 4 ) with nitrous acid gave 8-phenyltetrazolo[1,5-e]pyrazolo[1,5-a]-1,3,5-triazine ( 5b ), which was determined by pmr and ir spectra to be in equilibrium with 4-azido-7-phenylpyrazolo[1,5-a]-1,3,5-triazine ( 5a ). The equilibrium between the tetrazolo ( 5b ) and azido ( 5a ) forms was studied by pmr and an attempt was made to determine if substituents in the pyrazole nucleus could sufficiently stabilize the tricyclic tetrazolo form ( 5b ) over the bicyclic azido form ( 5a ). Thermal degradation of 5 (a ? b) in an aprotic solvent gave 4-amino-7-phenylpyrazolo[1,5-a]-1,3,5-triazine ( 7 ), indicating the probability of a nitrene mechanism involved in the decomposition. Heating 5 in aqueous base gave both 7 and the “hydroxy” analog, 7-phenylpyrazolo[1,5-a]-1,3,5-triazin-4(3H)one ( 6 ), further substantiating the existence of a nitrene intermediate with a competing nucleophilic displacement of the azido group by a hydroxyl group. Cyclization of 4 with diethoxymethylacetate (DEMA) gave 8-phenyl-s-triazolo[4,3-e]pyrazolo[1,5-a]-1,3,5-triazine ( 8 ), which underwent thermal rearrangement to 8-phenyl-s-triazolo[2,3-e]pyrazolo[1,5-a]-1,3,5-triazine ( 9 ). Acid catalyzed ring opening of 9 with formic acid gave 3-N-formamido-5-phenyl-2(2-s-triazolyl)pyrazole ( 10 ). The failure of 10 to recyclize to 9 with the resultant loss of water, supported the theory that the rearrangement of 8 to 9 might occur simply as a concerted, thermally induced “anhydrous” rearrangement rather than via a covalently hydrated intermediate or a Dimroth type mechanism (in the base catalyzed rearrangement).     

Umlagerung von Allyl-aryläthern und Allyl-cyclohexadienonen mittels Bortrichlorid

Allyl aryl ethers which have no strongly electron attracting substituents undergo a charge-induced [3 s, 3 s] sigmatropic rearrangement in the prescence of 0.7 mole boron trichloride in chlorobenzene at low temperature, to give after hydrolysis the corresponding o-allyl phenols (Tables 1 and 2). The charge induction causes an increase in the reaction rate relative to the thermal Claisen rearrangement of ～10¹⁰. With the exception of allyl 3-methoxyphenyl ether (5) , m-substituted allyl aryl ethers show similar behaviour (with respect to the composition of the product mixture) to that observed in the thermal rearrangement (Table 3). The rearrangement of allyl aryl ethers with an alkyl group in the o-position, in the prescence of boron trichloride, yields a mixture of o- and p-allyl phenols, where more p-product is present than in the corresponding product mixture from the thermal rearrangement (Table 4). This ‘para-effect’ is especially noticeable for o-alkylated α-methylallyl aryl ethers (Table 5 ). With boron trichloride, 2,6-dialkylated allyl aryl ethers give reaction products which arise, in each case, from a sequence of an ortho-Claisen rearrangement followed by a [1,2]-, [3,3]- or [3,4]-shift of the allyl moiety (Tables 6 and 7). Ally1 mesityl ether (80), with boron trichloride, gives pure 3-ally1 mesitol ( 95 ). From phenol, penta-ally1 phenol ( 101 ) can be obtained by a total of five O-allylations followed by three thermal and two boron trichloride-induced rearrangements. The sigmatropic rearrangements of the ethers studied, using D- and ¹⁴C-labelled compounds, are collected in scheme 2; only the reaction steps indicated by heavy arrows are of importance. With protic acids, there is a [3,3]-shift of the allyl group in 6-allyl-2,6-disubstituted cyclohexa-2,4-dien-l-ones, while with boron trichloride the [3,3]-reaction is also observed along with the much less important [1,2]- and [3,4]-transformations (Table 8). 4-Allyl-4-alkyl-cyclohexa-2,5-dien-1-ones give only [3,3]-rearrangements with boron trichloride (Table 9). As expected, the naphthalenone 112 , which is formed by allowing boron trichloridc to react for a short time with allyl (1-methyl-2-naphthyl) ether ( 111 ), undergoes only a [3,4] rearrangement (Scheme 3). Representations of how, in our opinion, the complex behaviour of allyl aryl ethers and allyl cyclohexadienones under the influence of boron trichloride, can be rationalized are collected together in Schemes 4 and 5. In the last part of the discussion section, the steric factors leading to the appearance of the ‘para-effect’, are dealt with (Scheme 6).     

The Synthesis of (3,5-DI-tert-butyl-4-hydroxyphenyl)methyl-(3-pyridylalkyl)-ethers via 1-(3,5-Di-tert-butyl-4-hydroxyphenyl)methyl Pyridinium Salts.

The rearrangement of 1-(3,5-di-tert-butyl-4-hydroxyphenyl)methyl pyridinium salts under basic conditions is described. A method for the synthesis of (3,5-di-tert-butyl-4-hydroxyphenyl)methyl-(3-pyridylalkyl)-ethers is elaborated.     

A Facile and Practical Procedure for the Synthesis of 8-Hydroxy-4-oxochroman Derivatives

Abstract: Novel 8-hydroxy-4-oxochroman derivatives were prepared from appropriate 4-chromanones via the Baeyer-Villiger oxidation followed by an intramolecular Fries rearrangement.     

Methylierung von 4-Hydroxy-4-(2-piperidyl)-4H-pyrazolo [1,5-a]indol mit Formaldehyd und Ameisensäure. 11. Mitteilung über metallorganische Reaktionen und Folgeprodukte

In the 10^th communication of this series [1] the synthesis of 4-hydroxy-4-(2-piperidyl)-4H-pyrazolo[1,5-a]indole ( 4 ) was described (Scheme). Surprisingly enough, methylation of this compound with formaldehyde and formic acid led via ring closure and a subsequent rearrangement to a pentacyclic ketone. By means of ¹³C-NMR.-spectroscopy and mass spectroscopy, this ketone could be identified as a indolizino-pyrazolo-indole ( 9 ). Its structure and configuration were determined by X-ray structure analysis.