Ringerweiterung von 1,2-Thiazol-3(2H)-on-1,1-dioxiden und 3-Amino-2H-azirinen zu 4H-1,2,5-Thiadiazocin-6-on-1,1-dioxiden

Ring Enlargement of 1,2-Thiazol-3(2H)-one-1,1-dioxides and 3-Amino-2H-azirines to 4H-1,2,5-Thiadiazocin-6-one-1,1-dioxides Reaction of 3-amino-2H-azirines 2 with the 1,1-dioxides 4 and 7 of 1,2-thiazol-3(2H)-ones and 1,2-thiazoli-din-3-ones, respectively, in i-PrOH at room temperature leads to 4H-1,2,5-thiadiazocin-6(5H)-one-1,1-dioxides 5 (Scheme 2, Table) and the corresponding 7,8-dihydro derivatives 8 (Scheme 4), respectively. The structure of some of the new 8-membered heterocycles as well as the structure of the minor by-product 6 (Scheme 3) have been established by X-ray crystallography (Chapt. 4). The proposed reaction mechanism for the ring expansion to 5 and 8 (Scheme 2) is in accordance with previously published results of reactions of 2 and NH-acidic heterocycles and is further supported by the results of the reaction of 4a and the (1-¹⁵N)-labelled aminoazirine 2a *.     

4-Amino-1,5-dihydro-2H-pyrrol-2-one aus Bortrifluorid-katalysierten Umsetzungen von 3-Amino-2H-azirinen mit Carbonsäure-Derivaten

4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid Derivatives Reaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate ( 6a ) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8 , the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C? C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF₃ catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF₃ catalysis is proposed in Scheme 6.     

Umsetzung von 3-Amino-2H-azirinen mit Salicylohydrazid

Reaction of 3-Amino-2H-azirines with Salicylohydrazide 3-Amino-2H-azirines 1a–g react with salicylohydrazide ( 7 ) in MeCN at 80° to give 2H, 5H-1,2,4-triazines 10 , 1,3,4-oxadiazoles 12 and, in the case of 1d , 1,2,4-triazin-6-one 11a (Scheme 3). The precursor of these heterocycles, the amidrazone of type 9 , except for 9c and 9g , which could not be isolated, has been found as the main product after reaction of 1 and 7 in MeCN at room temperature. 3-(N-Methyl-N-phenylamino)-2-phenyl-2H-azirin ( 1g ) reacts with 7 to give mainly the aromatic triazines 15b₁ and 15b₂ . In this case, two unexpected by-products, 16 and salicylamide ( 17 ), occurred, probably by disproportionation of a 1:1 adduct from 1g and 7 (Scheme 8). Oxidation of 10f with DDQ leads to the triazine 15a . The structure of 10c, 11a, 12c, 13 (by-product in the reaction of 1b and 7 ), the N′-phenylureido derivative 14 of 9d (Scheme 4) as well as 15b₂ has been established by X-ray crystallography. The ratio of 10/12 as a function of substitution pattern in 1 and solvent has been investigated (Tables 1, 3, 4, and 7). A mechanism for the formation of 10 and 12 is proposed in Scheme 7.     

Reaktion von 3-Amino-2H-azirinen mit Diphenylcyclopropenthion. Vorläufige Mitteilung

Reaction of 3-Amino-2H-azirines with Diphenylcyclopropenethione 3-Dimethylamino-2H-azirines ( 4a , 4b ) react with diphenylcyclopropenethione ( 8 ) to give 4(3 H)-pyridinethione derivatives of type 10 (Scheme 3). The reaction mechanism for the formation of 10 is given in Scheme 3 by analogy with a previous reported one [4] [5]. Hydrolysis of the 4(3 H)-pyridinethione 10a yields 2-oxo-2, 3-dihydro-4(1 H)-pyridinethione ( 11 ) and reduction of 10a with sodium borohydride leads to the 2, 3-dihydro-4 (1 H)-pyridinethione 12 (Scheme 4). The results of the reaction of 4a , 4b and the thione 8 demonstrate the similarity to the reaction of 4a , 4b and 2 [5] (cf. Scheme 1). In contrast, the reactions of imines of type 7a with 2 and 8 , respectively, lead to different products (cf. [1] [6]).     

Bortrifluorid-katalysierte Umsetzungen von 3-Amino-2H-azirinen mit Aminosäure-estern und Aminen

Boron-Trifluoride-Catalyzed Reactions of 3-Amino-2H-azirines with Amino-acid Esters and Amines After activation by protonation or complexation with BF₃, 3-amino-2H-azirines 1 react with the amino group of α-amino-acid esters 3 to give 3,6-dihydro-5-aminopyrazin-2(1H)-ones 4 by ring enlargement (Scheme 2, Table 1). The configuration of 3 is retained in the products 4 . With unsymmetrically substituted 1 (R¹ ≠ R²), two diastereoisomers of 4 (cis and trans) are formed in a ratio of 1:1 to 2:1. With β-amino-acid esters 5 and 7 , only openchain α-amino-imidamides 6 and 8 , respectively, are formed, but none of the seven-membered heterocycle (Scheme 3). Primary amines also react with BF₃-complexed 1 to yield α-amino-imidamides of type 9 (Scheme 4, Table 2). Compound 9b is characterized chemically by its transformation into crystalline derivatives 10 and 12 with 4-nitrobenzoyl chloride and phenyl isothiocyanate, respectively (Scheme 5). The structure of 12 is established by X-ray crystallography. Mechanisms for the reaction of activated 1 with amino groups are proposed in Schemes 6 and 7.     

Bortrifluorid-katalysierte Umsetzung von 3-Amino-2H-azirinen mit Amiden: Bildung von 4,4-disubstituierten 4H-Imidazolen

Boron Trifluoride Catalyzed Reaction of 3-Amino-2H-azirines and Amides: Formation of 4,4-Disubstituted 4H-Imidazoles Reaction of trifluoroacetamide and 3-amino-2H-azirines 1 in refluxing MeCN affords 4-amino-2-(trifluoromethyl)-4H-imidazoles 5 in fair yields (Scheme 3). Less acidic amides do not react with 1 under similar conditions. Therefore, a procedure involving BF₃-catalysis has been elaborated: the aminoazirine 1 in CH₂Cl₂ at ?78° is treated with BF₃ · Et₂O and then with a solution of the sodium salt of an amide in THF, prepared by addition of sodium hexamethyldisilazane at ?78°. The 4H-imidazoles of type 5 are formed in ca. 50% yield (Scheme 4). Reaction mechanisms for this ring enlargement of 1 are proposed in Schemes 5 and 6.     

4,4-Disubstituierte Imidazol-Derivate aus der Umsetzung von 3-Amino-2H-azirinen mit Salicylamid

4,4-Disubstituted Imidazole Derivatives from the Reaction of 3-Amino-2H-azirines with Salicylamide Reaction of 3-amino-2H-azirines 1a–c with salicylamide ( 7 ) in MeCN leads to imidazoles 10 and 11 in different rates, depending on the conditions. In the case of 1a and 1b, 11a and 11b , respectively, have been obtained as the main product at 50°; in reactions at 80°, 10a and 10b are the favored products (Tables 1 and 2). 2,2-Dimethyl-3-(N-methyl-N-phenylamino)-2H-azirine ( 1c ) reacts with 7 in MeCN mainly to 2-(2-hydroxyphenyl)-5,5-dimethyl-3,5-dihydroimidazol-4-one ( 10a ); in boiling toluene, 11c is formed with low preference (Table 3). The structure of the products has been established by spectroscopic means, and in the case of 10b and 11c , by X-ray crystallography. Two different reaction mechanisms for the formation of the products are discussed (Scheme 2).     

Additionsreaktionen von 2-Amino-1-azetinen mit Cyclopropenonen; Bildung von Azepinderivaten durch Ringerweiterung. Vorläufige Mitteilung

Addition Reactions of 2-Amino-1-azetines with Cyclopropenones; Formation of Azepine Derivatives by Ring Expansion Reactions The reaction of 2-amino-1-azetines of type 6 with 2,3-diphenylcyclopropenone ( 1a ) in acetonitrile leads to azetol[1,2-α]pyrroles (cf. 7 and 9 , Schemes 3 and 4) in good yield. It is remarkable that in the reaction of 6a with 1a only endo- 7 is formed. With silicagel in ether endo- 7 isomerizes to the thermodynamically more stable exo- 7 (Schemes 3 and 6). The crystal structure of the latter compound has been established by X-ray crystallography. The reaction of 6a and 2-isopropyl-3-phenyl-cyclopropenone ( 1b ) yields only one product, which isomerizes with silicagel in ether to exo- 10 (Scheme 4). The structure of exo- 10 has been determined by NMR-spectroscopy. It seems reasonable that this structure results from a nucleophilic attack of the four-membered amidine to the phenyl-substituted C-atom of 1b.     

Cis and trans 4,8-dimethyl-6-phenyl-5,6,7,8-tetra-hydro-4H-1,3,6-oxadiazocin-2-ones: Conformational studies and configurational assignments by NMR

The reaction of N-(2-aminopropyl)-N-(2-hydroxypropyl)aniline with phosgene afforded cis and trans isomers of 4,8-dimethyl-6-phenyl-5,6,7,8-tetrahydro-4H-1,3,6-oxadiazocin-2-one. On the basis of ASIS data and Eu-shift difference, the title compounds are found to exist as boat-chair conformation in which the carbonyl carbon resides at the BC-2 position on the molecular plane.     

3-氨基-1,3,4,5-四氢-2H-1-苯并氮杂革-2-酮的合成

以3-溴-1,3,4,5-四氢-2H-1-苯并氮杂--2-酮为起始原料,与苄胺反应制得3-苄氨基-1,3,4,5-四氢-2H-1-苯并氮杂(堇)-2-酮(2);2经5％ Pd/C催化加氢合成了3-氨基-1,3,4,5-四氢-2H-1-苯并氮杂——革)-2-酮(3),总收率90％.最佳氢化反应条件为:以无水乙醇为溶剂,5％ Pd/C用量为总用量的10％,于100℃/2.5 MPa条件下反应10 h,3的收率95.5％,纯度99.7％.5％ Pd/C可套用7次,收率稳定在95％左右.     

Ringerweiterungen und Ringverengungen bei der Umsetzung von 1, 3-Oxazolidin-2, 4-dionen und 1, 3-Thiazoiidin-2, 4-dion mit 3-Amino-2H-azirinen

Ring Enlargements and Ring Contractions in the Reaction of 1, 3-Oxazolidine-2, 4-diones and l, 3-Thiazolidine-2, 4-dione with 3-Amino-2H-azirines The reaction of 3-amino-2H-azirines 1 and 1, 3-oxazolidine-2, 4-diones 2 in MeCN at room temperature leads to 3, 4-dihydro-3-(2-hydroxyacetyl)-2H-imidazol-2-ones 3 in good yield (Scheme 2, Table 1). A reaction mechanism proceeding via ring enlargement of the bicyclic zwitterion A to give B, followed by transannular ring contraction to C, is proposed for the formation of 3 . This mechanism is in accordance with the result of the reaction of 2a and the ¹⁵N-labelled 1a *: in the isolated product 3a *, only N(3) is labelled (Scheme 1). The analogous reaction of 1 and 1, 3-thiazolidine-2, 4-dione ( 5 ) is more complex (Schemes 4 and 5, Table 2). Besides the expected 3, 4-dihydro-3-(2-mercaptoacetyl)-2H-imidazol-2-ones 7, 5-amino-3, 4-dihydro-2H-imidazol-2-ones of type 8 and/or N-(1, 4-thiazin-2-ylidene)ureas 9 are formed. In the case of 2-(dimethylamino)-1-azaspiro[2. 3]hex-1-ene ( 1d ), the postulated eight-membered intermediate 6d could be isolated. Its structure as well as that of 9f has been determined by X-ray structure analysis. A reaction mechanism for the formation of the 1, 4-thiazine derivatives of type 9 is proposed in Scheme 6.     

Synthesis of 6-phenyl-5,6,7,8-tetrahydro-4H-1,3,2,6-dioxathiazocine 2-oxides

Four 6-phenyl-5,6,7,8-tetrahydro-4H-1,3,2,6-dioxathiazocine 2-oxides were synthesized by the reaction of the corresponding N,N-bis(2-hydroxyethyl)aniline with thionyl chloride in the presence of triethylamine.     

Synthesis of 5''''-3H-2-Amino-6-cyclopropylaminopurine Nucleosides

We have described a novel use of the D4G prodrug (Cyclo-D4G) approach to stabilize the nucleoside and maintain the anti-HIV activity. β-D-Dioxolanyl-2-amino-6-cyclopropylaminopurine (10, DACP) was synthesized as a prodrug of β-D-dioxolanyl guanine (DXG) and showed potent anti-HIV activity in vitro (EC50=0.18 μmol·L-1 The pharmacokinetics of Cyclo-D4G and DACP following intravenous and oral administration of DACP to rhesusmonkeys and rats did not give D4G and DXG as detectable metabolic products by HPLC. Therefore the radio labeled Cyclo-D4G and DACP are necessary for the pharmacokinetics studies in detail.     

Oxidative Addition of N-Aminophthalimide and 3-Amino-2-methylquinazolin-4(3H)-one to Conjugated Azocyclopentenes and Azocyclohexenes

The oxidation of N-aminophthalimide and 3-amino-2-methylquinazolin-4(3H)-one in the presence of conjugated azocyclopentenes, azocyclohexenes, and 3-arylazocyclohexen-2-ones gives adducts at the carbon-carbon double bond corresponding to C-azoaziridines and/or bicyclic 2H-1,2,3-triazoles.     

1-甲基-5,6,7,8-四氢异喹啉酮-4-甲胺的合成研究

以环己酮为起始原料,经缩合、酰化及酸性水解反应制得2 乙酰基环己酮（1）;在三乙烯二胺催化下,1与氰基乙酰胺环化得四氢异喹啉酮（2）和四氢喹啉酮（3）混合物,在乙醇中回流并趁热过滤进行分离纯化得2和3; 2经催化加氢反应合成1-甲基-5,6,7,8-四氢异喹啉酮-4-甲胺,3步总收率39.8%,其结构经¹H NMR、¹³C NMR、 ¹H-¹⁵N HMBC和MS确证。     

水中"一锅法"合成2-氨基-3-氰基-4-芳基-7,7-二甲基-5-氧代-4H-5,6,7,8-四氢苯并[b]吡喃

报道了以十二烷基苯磺酸(DBSA)为催化剂,芳醛、丙二腈和5,5-二甲基-1,3-环己二酮为原料于水中一步生成2-氨基-3-氰基-4-芳基-7,7-二甲基-5-氧代-4H-5,6,7,8-四氢苯并[b]吡喃.该方法具有产率高、操作简便、对环境友好、催化剂可重复使用等优点.     

Mass spectral fragmentations of 6-phenyl-5,6,7,8-tetrahydro-4H-1,3,6-dioxazocin-2-ones

The mass spectra of a series of 6-phenyl-5,6,7,8-tetrahydro-4H-1,3,6-dioxazocin-2-ones have been examined.     

Synthesis of 1,2,5-Thiadiazepine Derivatives by Ring Enlargement of 1,2-Thiazetidin-3-one 1,1-Dioxides with 3-Amino-2H-azirines

At 0° in MeCN, 2,2-disubstituted 3-amino-2H-azirines 1 and 4,4-disubstituted 1,2-thiazetidin-3-one 1,1-dioxides 7 react smoothly to give 1,2,5-thiadiazepin-6-one 1,1-dioxides of type 8 (Scheme 2). The reaction mechanism of this regiospecific ring enlargement to seven-membered heterocycles follows previously described pathways. The structures of 7a and 8b were established by X-ray crystallography (see Figs. 1 and 2).