A new approach to 1-alkyl-1,3-dihydro-2H-benzimidazol-2-ones

A new procedure for preparing 1-alkyl-1,3-dihydro-2H-benzimidazol-2-ones fromo-nitroanilines by successive ethoxycarbonylation, catalytic hydrogenation and thermal cyclization under neutral conditions is described.

---

Eine neue Synthese von 1-Alkyl-1,3-dihydro-2H-benzimidazol-2-onen

Zusammenfassung Eine neue Methode zur Darstellung von 1-Alkyl-1,3-dihydro-2H-benzimidazol-2-onen auso-Nitroanilinen durch Ethoxycarbonylierung, katalytische Hydrierung und thermische Cyclisierung wird beschrieben.

     

Polymerization of butene-2 with isomerization to butene-1

An attempt has been made to prepare a high molecular weight isotactic polybutene-1 from cis- or trans-butene-2. Polymerization of butene-2 did not occur due to the steric effect of the substituents. In the presence of TiCl₃–Al(C₂H₅)₃ catalyst, however, both butene-2 monomers were found to polymerize at a slower rate than butene-1 and to give polymers consisting of the repeating unit of butene-1. From the gas chromatographic determination of the isomer distribution of the butenes recovered after the polymerization, it was found that the butenes isomerized, in the presence of the catalyst system containing TiCl₃, to approach the thermodynamic equilibrium mixture of butene-1, cis-butene-2, and trans-butene-2. It was also found that the rates of polymerization of butene-2 for the catalyst systems used were proportional to the isomerization rates. These results show that butene-2 isomerizes first to butene-1 which has less steric hindrance and then polymerizes as butene-1, through ordinary vinyl polymerization by a coordinated anionic mechanism. This type of polymerization was observed in some other linear β-olefins such as n-pentene-2 and n-hexene-2.     

Photocycloaddition of Quinoxaline-2(1H)-thiones to Alkenes

A synthetically useful C? C bond formation involving the photochemical addition of quinoxaline-2(1H)-thiones to alkenes is described. Irradiation of the quinoxaline-2(1H)-thiones 1–4 in the presence of the alkenes 7 gave the 2-(2′-mercaptoalkyl)quinoxalines 8–11 in moderate-to-good yields via ring cleavage of an intermediate aminothietane with aromatization of the quinoxaline ring. The latter was formed by [2+2] photocycloaddition of the C?S bond of the quinoxaline-2(1H)-thione and the C?C bond of the alkene.     

Heterocyclization of 2-chloro-1-cyano-1-diethoxyphosphoryl-2-trifluoromethylethylene and 2-chloro-2-chlorodifluoromethyl-1-cyano-1-diethoxyphosphorylethylene

The reactions of 2-chloro-1-cyano-1-diethoxyphosphoryl-2-trifluoromethylethylene (2a) and 2-chloro-2-chlorodifluoromethyl-1-cyano-1-diethoxyphosphorylethylene (2b) with arylamines, arylhydrazines, amidines, 2-aminopyridines, and 5-aminopyrazoles were studied. Alkenes 2a, b can serve as precursors of aminopyrazoles, pyrimidines, pyrido[1,2-a]pyrimidines, and pyrazolo[1,5-a]pyrimidines modified with the fluoroalkyl and diethoxyphosphoryl groups. Intermediates of some heterocyclization reactions were detected by NMR spectroscopy. The structures of the compounds were confirmed by X ray diffraction analysis.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1977–1986, September, 2004.     

Relativistic calculation of autoionization widths of 1s2s2pjJ, 1s2s2 2S1/2, and 1s2pJ 2pj′J levels

The autoionization widths of levels 1s 2s 2p_jJ, 1s2s^{2 2}S_1/2, and 1s2p_j2p_j′ J have been calculated for ions with Z = 6–30. The calculation has been carried out in intermediate coupling. The decay amplitudes have been calculated in a relativistic approximation.     

Crystal Structure of 1-nitro-2-phenylcycloprop-2-enecarbonitrile

The synthesis and x-ray crystal structure of 1 -nitro-2-phenylcycloprop-2-enecarbonitrile [1] is reported. The C-NO₂ bond length in1 is similar to but slightly shorter than that reported for 1, 2-diphenyl-3-nitrocyclopropene (2). Unlike2, 1 shows no tendency to ionize to the corresponding cyclopropenium ion in solution. This result is further supported by ab initio calculations.     

An Easy Entry to (1S, 2S) and (1R, 2R)-Threo-Ifenprodil

A facile and practical synthesis of enantiomerically pure (L) or (D)-threo-Ifenprodil was accomplished from (1S, 2S)- and (1R, 2R)-threo-1-(p-nitrophenyl)-2-amino-propan-1, 3-diol via 3-phenylthio derivatives followed by Raney nickel reduction and conversion of the aromatic amine into phenol.     

Photochemisches Verhalten von 1- und 2-alkylierten 1, 2-Dihydronaphthalinen bei tiefen Temperaturen

The irradiations of 1, 1-dimethyl- (8), 1, 1-di-(tri-deuteriomethyl)- (d₆– 8 ), 1, 1, 2, 2-tetramethyl- ( 9 ) and cis- and trans-1, 2-dimethyl-1, 2-dihydronaphthalenes (cis- and trans- 10 ) were investigated in 2, 2-dimethylbutane/pentane at ?100° using a mercury high-pressure lamp, and with mercury high- and low-pressure lamps at room temperature. The results were compared with one another, and those of the individual compounds are collected in schemes 2 and 4–7. The most important results are the following: 1. The 1, 2-dihydronaphthalenes undergo a conrotatory ring opening to the o-quinodimethanes on irradiation with high- or low-pressure lamps at room temperature or at ?100°. Thermal reactions ([1, 7a]H-shifts, electrocyclisations) are suppressed at ?100°. The o-quinodimethanes formed from 8 (scheme 2), 9 (scheme 5) or cis- 10 (scheme 6) undergo on irradiation with the high-pressure lamp, [1, 5]H-shifts or photochemical Diels-Alder reactions after renewed photochemical excitation, to yield the benzobicyclo[3.1.0]hex-2-ene derivatives. These Diels-Alder reactions do not proceed stereospecifically, and therefore are not orbital symmetry controlled reactions. 2. If the 1, 2-dihydronaphthalenes are irradiated at room temperature with either a high- or a low-pressure lamp, then the initially formed o-quinodimethanes undergo thermal [1, 7a]H-shifts, in preference to all other reactions, as long as this is sterically possible; the resulting products can undergo secondary photochemical transformations. Such o-quinodimethanes are formed on irradiation of 8, 9 and cis- 10 . From trans- 10 , an o-quinodimethane mixture is formed, of which one component (cis, cis- 22 ) undergoes thermal [1, 7a] H-shifts, while the other (trans, trans- 22 ) suffers a thermal disrotatory electrocyclisation to give cis- 10 . If a high-pressure lamp is used in the last experiment, then the competing photochemical Diels-Alder cyclisation to bicyclic compounds of the type 23 (scheme 7) can result in the trans, trans- 22 . As was shown by Salisbury [3], and confirmed by ourselves in other cases [2], photochemical Diels-Alder reactions or [1, 5]H-shifts in the o-quinodimethanes require light of wavelength ? 400 nm (high-pressure lamp). The present photochemical investigations amplify and confirm our earlier conclusions concerning the photochemistry of the 1, 2-dihydronaphthalenes [2].     

Synthetic approaches to 2-substituted 1-oxo- and 3-oxotetrahydroisoquinolines

2-Substituted homophthalimides 2a-c were reduced regioselectively with sodium borobydride to carbinol-lactam intermediates 3a-c , which were dehydrated, followed by hydrogenation, to give 1-oxo-tetrabydroisoquinolines or 3,4-dihydroisoquinolin-1(2H)ones 5a-c . The isomeric 3-oxo-tetrahydro-isoquinolines or 1,4-dihydroisoquinolin-3(2H)-ones 8a-i were obtained in satisfactory yields via heating 3-isochromanone ( 6 ) with the corresponding amines 7a-i in the presence of aluminum chloride.     

Regiospecific synthesis of 2-methyl-4-arylcarbonyl-2H-1, 2-benzothiazin-3(4H)-one 1, 1-dioxides

Acylation of 2-methyl-2H-1, 2-benzothiazin-3(4H)-one 1, 1-dioxide 3 with aryl anhydrides in the presence of dimethylaminopyridine occurs regiospecifically to afford 2-methyl-4-arylcarbonyl-2H1, 2-benzothiazin-3(4H)-one 1, 1-dioxides 2a-f .     

Einige bestrahlungsexperimente mit 2, 1-Benzisothiazolen

Some Irradiation Experiments with 2, 1-Benzisothiazoles 2, 1-Benzisothiazole ( 1 ) on irradiation with a mercury high-pressure lamp in benzene/diethylamine yields, after acetylation, 2-acetylamino-benzaldehyde ( 3 ; Scheme 1). Similarly, irradiation of 3-chloro-2, 1-benzisothiazole ( 2 ) in benzene/diethylamine leads to a mixture of 3-dimethylamino-2, 1-benzisothiazole ( 6a ) and N, N-diethyl-thioanthranilamide ( 7a ; Scheme 2). Benzisothiazole 6a , on irradiation, is not transformed into 7a . On the other hand, when 2 is irradiated in methanol a mixture of 3-methoxy-2, 1-benzisothiazole ( 4a ) and methyl anthranilate ( 5a ; Scheme 2) is obtained. In this case, 4a on irradiation in methanol or ethanol also yields 5a . No exchange of the methoxy group in 4a is observed when the irradiation is performed in ethanolic solution. Thus, 2, 1-benzisothiazoles 1 , 2 and 4a react photochemically by N,S-bond cleavage and hydrogen-atom abstraction from the solvent (Scheme 3). 3-Chloro-2, 1-benzisothiazole ( 2 ) shows a second photoreaction, i.e. nucleophilic exchange of the chloro substituent by methanol or diethyl amine. The latter reaction can also be observed thermally, e.g. in boiling methanol in the presence of methoxide ions.     

Reactions of 2-Arylthio- and 2-Arylsulfonyl-1-nitro-1-phenylethenes with Amines

2-Arylthio- and 2-arylsulfonyl-1-nitro-1-phenylethenes react with amines to give the corresponding nitroenamines whose configuration (E or Z) depends on the amine structure. Primary amines gives rise to Z-nitroenamines, secondary cyclic amines with 2-arylthio-1-nitroalkenes form E-nitroenamines, and with more reactive 2-arylsulfonyl-1-nitroalkenes E/Z-isomeric mixtures are obtained.     

1-Amino-2-hydrazinopyrimidin-N-ylides. Unusual tautomers of 1-aminopyrimidin-2-hydrazones

Summary 1-Amino-2-methylthiopyrimidinium iodides3 have been synthesized by reaction of 3-isothiocyanato-2-propeniminium perchlorates1 with hydrazines and subsequent methylation of the resulting 1-amino-2(1H)-pyrimidinthiones2. Reaction of3 with hydrazine causes substitution of the methylthio group and results in the formation of deeply coloured 1-amino-2-hydrazinopyrimidin-N-ylides5 as unusual tautomers of the commonly expected 1-amino-2(1H)-pyrimidinhydrazones4. The structure of these N-ylides has been proved by spectroscopic methods as well as by subsequent transformation to 3-amino-1,2,4-triazolo[2,3-a]pyrimidinium salts9 by dehydration or to pyrimidotriazinium salt10 c by oxidation. Reaction of N,N-disubstituted 1-amino-2-methylthiopyrimidinium salt7 a with hydrazine also causes substitution of methylthiol, the resulting orange N,N-disubstituted 1-amino-2(1H)-pyrimidinhydrazone8 a, however, cannot tautomerize to N-ylides.

---

1-Amino-2-hydrazinopyrimidin-N-ylide. Ungewöhnliche Tautomere von 1-Aminopyrimidin-2-hydrazonen

Zusammenfassung Es wurden 1-Amino-2-methylthiopyrimidiniumjodide3 ausgehend von 3-Isothiocyanato-2-propeniminiumperchloraten1 und Hydrazinen durch Methylierung der primär gebildeten 1-Amino-2(1H)-pyrimidinthione2 hergestellt. Die Reaktion dieser Pyrimidiniumsalze3 mit Hydrazin verläuft unter Substitution der Methylthiogruppe unter Bildung violett gefärbter 1-Amino-2-hydrazinopyrimidin-N-ylide5 als ungewöhnliche Tautomere der allgemein erwarteten 1-Amino-2(1H)-pyrimidinhydrazone4. Die Struktur dieser Ylide5 wird durch spektroskopische Methoden sowie durch nachfolgende Dehydratisierung zu 3-Amino-1,2,4-triazolo[2,3-a]pyrimidiniumsalzen9 bzw. Oxydation zum Pyrimidotriaziniumsalz10 c bewiesen. Die Reaktion des N,N-disubstituierten 1-Amino-2-methylthiopyrimidiniumsalzes7 a mit Hydrazin verläuft ebenfalls unter Substitution der Methylthiogruppe. Jedoch kann das gebildete orange gefärbte, N,N-disubstituierte 1-Amino-2(1H)-pyrimidinhydrazon8 a nicht zu einem N-Ylid tautomerisieren.

     

[2 + 2]-Cycloadditions to Strained Bridgehead Olefins. I. 1, 1-Dichloro-2,2-difluoroethene

The strained bridgehead olefins bicyclo [3.3.1]non-1-ene ( 1 ), bicyclo [4.2.1] non--1-(8) ( 2 ), and bicyclo [4.2.1]non-1-ene ( 3 ) react rapidly with 1,1-dichloro-2, 2--difluoroethene ( 5 ) to yield mixtures of regioisomeric dichlorodifluorocyclobutanes 8/9, 10/11 and 12/13 , respectively. On the contrary, the reaction of 5 with the model compound (E)-l-methylcyclooctene ( 4 ) is completely regioselective. The structure of the cycloadducts has been elucidated mainly by ¹⁹F-NMR. and ¹³C-NMR. spectroscopy.     

2-Alkyliden-1, 3-dithia-Heterocyclen aus 5-Sulfonyl-1, 2-dithiol-3-onen und Alkoholaten

Asymmetrically substituted 5-sulfonyl-1, 3-dithiafulvenes (9a–g), all of which have the same configuration (called α), are obtained by reaction of 4-chloro-5-sulfonyl-1, 2-dithiol-3-ones (3a–e) with sodium alkoxides. Side-products formed are 4-chloro-5-alkoxy-1, 2-dithiol-3-ones (5a and 5b), 3, 5-bis-alkylidene-1, 2, 4-trithiacyclopentanes (21 and 22), and (in some instances) minor amounts of compounds 33, 34, or 35. Reaction of 4-phenyl-5-methylsulfonyl-1, 2-dithiol-3-one with sodium methoxide results in the formation of 4-phenyl-5-methoxy-1, 2-dithiol-3-one (5c), the two cis-trans-isomers of 2, 4-bis-alkylidene-1, 3-dithiacyclobutane 24 and 25, and the 2, 5-bis-alkylidene-1, 2, 4, 5-tetrathiacyclohexane 26. Some conceivable reaction mechanisms are discussed, and proof is given for the structure of the major compounds. By treating 4-chloro-5-(2′-chloro-ethylthio)-1, 2-dithiol-3-one with sodium methoxide, the 2-alkylidene-1, 3-dithiolane 13 is obtained. The sulfonyl groups of the 1, 3-dithiafulvenes 9a–g described may be easily replaced by hydrogen or secondary amines, yielding compounds 14, 16 and 19, respectively. When dissolved in strong acids and reprecipitated, asymmetrically substituted 2-alkylidene-1, 3-dithia compounds may be converted into mixtures of all possible cis-trans-isomers thereof. Those isomers may be separated by fractional crystallization. Isomers 31 (called β) of 9 a--g, and 32 of 16a, b, are obtained accordingly.     

Solid-State Photocyclodimerization of 1-Thiocoumarin (= 2H-1-Benzothiopyran-2-one)

Irradiation (λ > 390 nm) of 2H-1-benzothiopyran-2-one ( 1 ) in the solid state affords selectively 6aα,6bα,12bα,12cα -tetrahydrocyclobuta[1,2-c:4,3-c′]bis[1]benzothiopyran -6,7-dione ( 2 ), the head-to-head (HH) cis-cisoid-cis-dimer, while irradiation of 1 in the solid state using shorter wavelengths (λ > 340 nm) affords a mixture of all four cis-fused tricyclic dimers 2 – 5 . These results represent a novel wavelength effect in solid-state photochemistry.     

Umwandlung der diastereomeren 12- und 6-gliedrigen 1-Acetyl-2-methyl-1-cycloalkanole in 1-Äthinyl-2-methyl-1-cycloalkene

Conversion of the Diastereoisomeric 12-and 6-membered 1-Acetyl-2-methyl-1-cycloalkanols to 1-Ethynyl-2-methyl-1-cycloalkenes This paper is concerned primarily with a derivation of the E-configuration of 1-ethynyl-2-methyl-1-cyclododecene ( 10 ), which plays a role in mechanistic considerations on a method for ring expansion by 3 carbon atoms described in apreceding paper [1]. The derivation is based on an argument using the results of the dehydration of trans-1-acetyl-1-2-methyl-1-cyclododecanol ( 4 ) to 10 with phosphorus oxychloride and pyridine. That this dehydration is stereospecific can be concluded from its regiospecificity since the cis-hydroxyketone 3 dehydrates mainly to 1-ethynyl-12-methyl-1-cyclododecene (mixture of stereoisomers 11 and 12 ). An x-ray analysis shows the indicated configurations of the two hydroxyketones 3 and 4 . The direction (anti) of the stereospecificity of the double bond introduction during the 4 → 10 conversion is deduced from the similarity of the behaviour of the two stereoisomeric 1-acetyl-2-methyl-1-cyclohexanols 8 and 9 under the same conditions and from mechanistic considerations, which make it likeley that the anti-elimination behaviour observed in the 6-membered system has not changed over to a syn-elimination behaviour in the 12-membered system. The configurations of the two 6-membered hydroxyketones 8 and 9 correspond to those of the precursor1-ethynyl-2-methyl-1-cyclohexanols 6 and 7 , which were clarified with the help of ¹³C-NMR.-spectral coupling observations. It is of interest that the hydroxyketones 3, 4, 8 and 9 react with phosphorus oxychloride and pyridine so as to introduce both a double and a triple bond. It is probable that the double bond is introduced first, inasmuch as the triple bond is not introduced in the absence of activation of the hydroxyl group, as for instance in acetylcyclohexane. This can be used as an argument that the conversion of the acetyl to an ethynyl group in 3, 4, 8 and 9 does not affect the stereospecificity of the dehydration which introduces the ring double bond. 1-Acetyl-2-methyl-1-cyclododecene ( 24 ), a previously isolated compound with pleasant odor, was synthesized by hydration of 10 . This furnishes an argument for the E-configuration of 24 .     

2-Phenylazo-1-alkene

Zusammenfassung Durch Umsetzung der Methylketon-phenylhydrazone1 mit J₂ in Pyridin werden die kristallinen 2-Phenylhydrazonoalkyl-pyridiniumjodide (2) synthetisiert und daraus mit Alkali unter 1,4-Eliminierung von Pyridin·HJ die in Substanz unbeständigen (E)-2-Phenylazo-1-alkene (4) hergestellt. Die spektroskopischen Untersuchungen (IR, Raman, EA und¹H-NMR) der orange-farbenen Öle4 beweisen dietrans-Konfiguration um die N=N-Bindung und außerdem, daß in Lösung4 a–d vorwiegend die s-trans (transoide) Konformation einnehmen, während4 e bevorzugt in der s-cis (cisoiden) Form vorliegt.

---

2-phenylazo-1-alkenes

The reaction of the methyl ketone phenylhydrazones1 with I₂ in pyridine yields the crystalline 2-phenylhydrazonoalkyl-pyridinium iodides (2). Upon alkali induced 1,4-elimination of pyridine·HI the (E)-2-phenylazo-1-alkenes4 are obtained as orange liquids which are unstable when free of solvent. Spectroscopic investigations (ir, Raman, ea and¹H-nmr) reveal thetrans-configuration at the N=N-bond and moreover assign the s-trans (transoid) conformation to4 a–d whereas4 e is correlated to the s-cis (cisoid) conformer.

---

---

Oxidationsprodukte von Arylhydrazon-Verbindungen,6. Mitt.; 5. Mitt.     

Research on nitrogen containing heterocyclic compounds. XVI. Synthesis of 1, 3, 4, 14b-tetrahydro-2, 10-dimethyl-2H,10H-pyrazino[2, 1-d]pyrrolo[1, 2-b][1, 2, 5]benzotriazepine (1:1) maleate (10-methyl-10-azaaptazepine)

A synthesis of the potential antidepressant 1, 3, 4, 14b-tetrahydro-2, 10-ditnethyl-2H,10H-pyrazino[2, 1-d]-pyrrolo[1, 2-b][1, 2, 5]benzotriazepine 4 , structurally related to aptazepine, is reported in four steps. The key steps of the synthesis were the formation of the tricyclic compound ethyl 10, 11-dihydro-5-methyl-5H-pyrrolo[1, 2-6-b][1, 2, 5]benzotriazepine-11-carboxylate 6 via a Pictet-Spengler type condensation and the formation of the diketopiperazine 8 by cyclization of the chloroester 7 with methylamine.     

Conversion of 6-phenylimino-2H-thiopyran-4-amines to 1-phenyl-2,3-dihydro-4(1H)-pyridinones

Summary 6-Phenylimino-3,6-dihydro-2H-thiopyran-4-amines (1) were converted to 1-phenyl-5,6-dihydropyridine-2(1H)-thiones (3). Those were akylated and hydrolyzed, thus yielding 6-methylthio-1-phenyl-2,3-dihydro-4(1H)-pyridinones (5). Finally, the methylthio group was removed withRaney nickel giving the title compounds6. The relative configurations of the formed diastereoisomeric dihydropyridinones have been investigated by NOE measurements.

---

Umwandlung von 6-Phenylimino-2H-thiopyran-4-aminen zu 1-Phenyl-2,3-dihydro-4(1H)-pyridinonen

Zusammenfassung 6-Phenylimino-3,6-dihydro-2H-thiopyran-4-amine (1) wurden in 1-Phenyl-5,6-dihydropyridin-2(1H)-thione (3) umgewandelt. Diese wurden alkyliert und zu 6-Methylthio-1-phenyl-2,3-dihydro-4(1H)-pyridinonen (5) hydrolysiert. Zuletzt gelangte man durch selektives Entfernen der Methylthiogruppe mitRaney-Nickel zu den Titelverbindungen6. Die relativen Konfigurationen der gebildeten diastereomeren Dihydropyridinone wurden durch NOE-Messungen aufgeklärt.