1,3‐Dipolar Cycloaddition Reactions of Indan‐1‐one Enamines across Arylnitrile Oxides Leading to Novel Cyclic Isoxazoline Derivatives

Synthesis of a series of cyclic fused‐isoxazolines has been accomplished by regioselective and diastereoselective 1,3‐dipolar cycloaddition of 3‐methylindan‐1‐one enamines ( 1a , 1b , 1c ) and 3‐phenylindan‐1‐one enamines ( 2a , 2b , 2c ) to arylnitrile oxides ( 3d , 3e , 3f , 3g , 3h ). The structure of the cycloadducts was elucidated by ¹H and ¹³C NMR spectroscopy. The proposed regio‐ and stereochemistry of fused‐compounds ( 4 ) and ( 5 ) has also been corroborated by two single‐crystal X‐ray diffraction studies carried out on 4‐methyl‐8b‐morpholinyl‐3‐(p‐tolyl)‐4H‐3a,8b‐dihydroindeno[2,3‐d]isoxazoline ( 4be ) and 3‐(p‐anisyl)‐4‐phenyl‐8b‐pyrrolidinyl‐4H‐3a,8b‐dihydroindeno[2,3‐d]isoxazoline ( 5af ) and by means of density functional theory calculations.     

Regioselective Synthesis of Mono‐ and Dispiropyrazoline Derivatives via 1,3‐dipolar Cycloaddition with Nitrilimines

The 1,3‐dipolar cycloaddition reaction of (E ,E )‐1,3‐bis(arylidene)indan‐2‐one 1a , 1b , 1c , 1d , 1e with diarylnitrilimines, generated in situ via dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a , 2b , 2c , affords predominantly monospiropyrazolines 3 and 4 as a mixture of diastereoisomers. Also dispiropyrazolines 5 are formed in moderate yields. The structure and stereochemistry of cycloadducts 3 , 4 , 5 were confirmed by ¹H and ¹³C‐NMR spectroscopy, elemental analyses data, and single‐crystal X‐ray diffraction studies of 3ba and 5ca .     

1,3‐Dipolar Cycloaddition of 4‐Chlorobenzonitrile Oxide with Some Dipolarophiles: Theoretical Analysis of Regioselectivity

Reaction of 4‐chlorobenzonitrile oxide ( 2 ) which was generated in situ with acrylo nitrile ( 3 ), vinyl acetate ( 4 ) and allyl bromide ( 5 ) as dipolarphile afforded the new cycloadducts 6a , 7a , and 8a compounds, respectively. Reactivity and regiochemistry of these reactions were investigated using activation energy calculations and density functional theory‐based reactivity indexes. The theoretical ¹³C NMR chemical shifts of the cycloadducts which were obtained by gauge‐invariant atomic orbital method were comparable with the observed values.     

Exploring the Border between Concerted and Two‐Step Pathways of 1,3‐Dipolar Cycloadditions of Organic Azides to Cyclic Ketene N,X‐Acetals. – Synthesis and 15N‐NMR Spectra of Zwitterions and Spirocyclic Cycloadducts

Cyclic ketene N,X‐acetals 1 are electron‐rich dipolarophiles that undergo 1,3‐dipolar cycloaddition reactions with organic azides 2 ranging from alkyl to strongly electron‐deficient azides, e.g., picryl azide ( 2L ; R¹=2,4,6‐(NO₂)₃C₆H₂) and sulfonyl azides 2M – O (R¹=XSO₂; cf. Scheme 1). Reactions of the latter with the most‐nucleophilic ketene N,N‐acetals 1A provided the first examples for two‐step HOMO(dipolarophile)–LUMO(1,3‐dipole)‐controlled 1,3‐dipolar cycloadditions via intermediate zwitterions 3 . To set the stage for an exploration of the frontier between concerted and two‐step 1,3‐dipolar cycloadditions of this type, we first describe the scope and limitations of concerted cycloadditions of 2 to 1 and delineate a number of zwitterions 3 . Alkyl azides 2A – C add exclusively to ketene N,N‐acetals that are derived from 1H‐tetrazole (see 1A ) and 1H‐imidazole (see 1B , C ), while almost all aryl azides yield cycloadducts 4 with the ketene N,X‐acetals (X=NR, O, S) employed, except for the case of extreme steric hindrance of the 1,3‐dipole (see 2E ; R¹=2,4,6‐(^tBu)₃C₆H₂). The most electron‐deficient paradigm, 2L , affords zwitterions 16D , E in the reactions with 1A , while ketene N,O‐ and N,S‐acetals furnish products of unstable intermediate cycloadducts. By tuning the electronic and steric demands of aryl azides to those of ketene N,N‐acetals 1A , we discovered new borderlines between concerted and two‐step 1,3‐dipolar cycloadditions that involve similar pairs of dipoles and dipolarophiles: 4‐Nitrophenyl azide ( 2G ) and the 2,2‐dimethylpropylidene dipolarophile 1A (R, R=H, ^tBu) gave a cycloadduct 13 H , while 2‐nitrophenyl azide ( 2 H ) and the same dipolarophile afforded a zwitterion 16A . Isopropylidene dipolarophile 1A (R=Me) reacted with both 2G and 2 H to afford cycloadducts 13G , J ) but furnished a zwitterion 16B with 2,4‐dinitrophenyl azide ( 2I) . Likewise, 1A (R=Me) reacted with the isomeric encumbered nitrophenyl azides 2J and 2K to yield a cycloadduct 13L and a zwitterion 16C , respectively. These examples suggest that, in principle, a host of such borderlines exist which can be crossed by means of small structural variations of the reactants. Eventually, we use ¹⁵N‐NMR spectroscopy for the first time to characterize spirocyclic cycloadducts 10 – 14 and 17 (Table 6), and zwitterions 16 (Table 7).     

Synthesis of New Derivatives of 4‐(4,7,7‐Trimethyl‐7,8‐dihydro‐6H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐2‐yl)morpholine

Cyclocondensation of 5‐amino‐6‐methyl‐2‐morpholinopyrimidine‐4‐thiol ( 1 ) and 2‐bromo‐5,5‐dimethylcyclohexane‐1,3‐dione ( 2 ) under mild reaction condition afforded 4,7,7‐trimethyl‐2‐morpholino‐7,8‐dihydro‐5H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐9(6H )‐one ( 3 ). The ¹H and ¹³C NMR data of compound ( 3 ) are demonstrated that this compound exists primarily in the enamino ketone form. Reaction of compound ( 3 ) with phosphorous oxychloride gave 4‐(9‐chloro‐4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 4 ). Nucleophilic substitution of chlorine atom of compound ( 4 ) with typical secondary amines in DMF and K₂CO₃ furnished the new substituted derivatives of 4‐(4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h ). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical data.     

Reactions of Methyl Diazoacetate with (E)‐ and (Z)‐1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: Novel and Unanticipated Pathways

The cycloadditions of methyl diazoacetate to 2,3‐bis(trifluoromethyl)fumaronitrile ((E)‐ BTE ) and 2,3‐bis(trifluoromethyl)maleonitrile ((Z)‐ BTE ) furnish the 4,5‐dihydro‐1H‐pyrazoles 13 . The retention of dipolarophile configuration proceeds for (E)‐ BTE with > 99.93% and for (Z)‐ BTE with > 99.8% (CDCl₃, 25°), suggesting concertedness. Base catalysis (1,4‐diazabicyclo[2.2.2]octane (DABCO), proton sponge) converts the cycloadducts, trans‐ 13 and cis‐ 13 , to a 94 : 6 equilibrium mixture (CDCl₃, r.t.); the first step is N‐deprotonation, since reaction with methyl fluorosulfonate affords the 4,5‐dihydro‐1‐methyl‐1H‐pyrazoles. Competing with the cis/trans isomerization of 13 is the formation of a bis(dehydrofluoro) dimer (two diastereoisomers), the structure of which was elucidated by IR, ¹⁹F‐NMR, and ¹³C‐NMR spectroscopy. The reaction slows when DABCO is bound by HF, but F^? as base keeps the conversion to 22 going and binds HF. The diazo group in 22 suggests a common intermediate for cis/trans isomerization of 13 and conversion to 22 : reversible ring opening of N‐deprotonated 13 provides 18 , a derivative of methyl diazoacetate with a carbanionic substituent. Mechanistic comparison with the reaction of diazomethane and dimethyl 2,3‐dicyanofumarate, a related tetra‐acceptor‐ethylene, brings to light unanticipated divergencies.     

Simple and Efficient Synthesis of Novel 3‐Substituted 2‐Thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones and Their Reactions with Alkyl Halides and α‐Glycopyranosyl Bromides

A series of 3‐substituted 2‐thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 4a – e were synthesized from the reaction of 3‐aminonaphthalene‐2‐carboxylic acid 1 with isothiocyanate derivatives 2a – e . The alkylation of 4a – e with alkyl halides gave 3‐substituted 2‐alkylsulfanyl‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 5a – o . S‐Glycosylation was carried out via the reaction of 4a – e with glycopyranosyl bromides 7a and 7b under anhydrous alkaline conditions. The structure of the compounds was established as S‐nucleoside and not N‐nucleoside. Conformational analysis has been studied by homonuclear and heteronuclear two‐dimensional NMR methods (2D DFQ‐COSY, heteronuclear multiple quantum coherence, and heteronuclear multiple bond correlation). The S site of alkylation and glycosylation was determined from the ¹H and ¹³C heteronuclear multiple quantum coherence experiments.     

Stereoselective Synthesis of [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]cyclosporin A

Addition of various amines to the 3,3‐bis(trifluoromethyl)acrylamides 10a and 10b gave the tripeptides 11a – 11f , mostly as mixtures of epimers (Scheme 3). The crystalline tripeptide 11f ₂ was found to be the N‐terminal (2‐hydroxyethoxy)‐substituted (R,S,S)‐ester HOCH₂CH₂O‐D ‐Val(F₆)‐MeLeu‐Ala‐O^tBu by X‐ray crystallography. The C‐terminal‐protected tripeptide 11f ₂ was condensed with the N‐terminus octapeptide 2b to the depsipeptide 12a which was thermally rearranged to the undecapeptide 13a (Scheme 4). The condensation of the epimeric tripeptide 11f ₁ with the octapeptide 2b gave the undecapeptide 13b directly. The undecapeptides 13a and 13b were fully deprotected and cyclized to the [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐D ‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐L ‐valine]]cyclosporins 14a and 14b , respectively (Scheme 5). Rate differences observed for the thermal rearrangements of 12a to 13a and of 12b to 13b are discussed.     

Synthesis and Characterization of New Thebaine Derivatives as Potential Opioid Agonists and Antagonists: 2‐[N‐(1H‐Tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazoles

In this study, we report the synthesis a series of novel 2‐[N‐(1H‐tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazole derivatives ( 7a – e ) which have potential opioid antagonist and agonist. The substitution reaction of 6,14‐endo‐ethenotetrahydrothebaine‐7α‐carbohydrazide with corresponding benzoyl chlorides gave diacylhydrazine compounds 4a – e in good yields. The treatment of compounds 4a – e with POCl₃ caused the conversion of side‐chain of compounds 5a – e into 1,3,4‐oxadiazole ring at C(7) position; thus, compounds 5a – e were obtained. Subsequently, cyanamides ( 6a – e ) were prepared from compounds 5a – e and then compounds 7a – e were synthesized by the azidation of 6a – e with NaN₃. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C APT, 2D‐NMR (COSY, NOESY, HMQC, HMBC) and high‐resolution mass spectral data.     

Photocycloaddition Reactions of Alkyl and Aryl 2‐Thioxo‐3H‐benzoxazole‐ 3‐carboxylates to Alkenes

The photochemical reactions of alkyl and aryl 2‐thioxo‐3H‐benzoxazole‐3‐carboxylates 1 have been examined. Irradiation of 1 in the presence of tetra‐ and trisubstituted alkenes 2a and 2b , 2‐methylprop‐2‐ene nitrile 2e , and dienes 2f and 2g gave [2+2] cycloadducts of the CS bond of 2‐thioxobenzoxazoles and the CC bond of alkenes, spiro[benzoxazole‐thietanes] 3, 4, 8 – 13, 15, 18, 20, 23 – 26 in moderate‐to‐good yields. The photoaddition reactions proceed in a regiospecific manner. The spirocyclic compounds obtained are indefinitely stable at room temperature. Irradiation of 1a in the presence of 1,1‐ and 1,2‐disubstituted alkenes 2c and 2d yielded the products 5 – 7 of oxazole‐ring cleavage. Compound 1d also underwent photoaddition with alkenes to yield spiro[benzoxazole‐thietanes] and/or 2‐substituted benzoxazoles and/or iminothietanes, depending on the nature of the substituents present in the alkenes. On intramolecular [2+2] photoadduct, tetracyclic 27 , was obtained, when ethenyl 2‐thioxobenzoxazole‐3‐carboxylate 1e was irradiated.     

Light‐Induced Cycloaddition of 2,3‐Dihydro‐2,2‐dimethyl‐4H‐thiopyran‐4‐one (a 4‐Thiacyclohex‐2‐enone) to Alkenes and Dienes

The reactivity of (thiacyclic)‐2,3‐dihydro‐2,2‐dimethyl‐4H‐thiopyran‐4‐one ( 1a ) in light‐induced cycloadditions to furan ( F ), acrylonitrile ( AN ), or 2,3‐dimethylbut‐2‐ene ( TME ) is compared to that of (carbocyclic) 5,5‐dimethylcyclohex‐2‐enone ( 1b ). Whereas for the more‐flexible thiacycle, the efficiency of [2+2]‐photocycloadduct formation with AN or TME is generally much lower, the diastereoselectivity regarding the ring fusion in the bicyclo[4.2.0]octanes is quite similar for both enones. In contrast, 1a affords exclusively trans‐fused [4+2] cycloadducts with F , while 1b gives predominantly the corresponding cis‐fused products.     

Conformational Studies of (±)‐11,12‐Didehydro‐11‐deoxycorynoline and (+)‐11,13‐Didehydro‐11‐deoxychelidonine,Hexahydrobenzo[c]phenanthridine‐Type Alkaloid Derivatives,by X‐Ray Crystal Structure and NMR Analyses

The X‐ray crystal analyses of the two 11‐deoxy‐didehydrohexahydrobenzo[c]phenanthridine‐type alkaloid derivatives 3 and 4 , derived from (±)‐corynoline ( 1 ) and (+)‐chelidonine ( 2 ), established their structures as (±)‐(5bRS,12bRS)‐5b,12b,13,14‐tetrahydro‐5b,13‐dimethyl[1,3]benzodioxolo[5,6‐c]‐1,3‐dioxolo[4,5‐i]phenanthridine ( 3 ) and (+)‐rel‐(12bR)‐7,12b,13,14‐tetrahydro‐13‐methyl[1,3]benzodioxolo[5,6‐c]‐1,3‐dioxolo[4,5‐i]phenanthridine ( 4 ). The conformations of 3 and 4 in CDCl₃ were determined on the basis of ¹H‐ and ¹³C‐NMR spectroscopy.     

Über Umlagerungen bei der Cyclialkylierung von Arylpentanolen zu 2,3‐Dihydro‐1H‐inden‐Derivaten, 4. Mitteilung

On Rearrangements by Cyclialkylations of Arylpentanols to 2,3‐Dihydro‐1 H ‐indene Derivatives. Part 4. The Acid‐Catalyzed Cyclialkylation of 2,4‐Dimethyl‐2‐phenyl[3‐ ¹³ C]pentan‐3‐ol The cyclialkylation of 2,4‐dimethyl‐2‐phenyl[3‐¹³C]pentan‐3‐ol ( 4 ) gives only 2,3‐dihydro‐1,1,2,3‐tetramethyl‐1H‐[3‐¹³C]indene ( 6 ) (cf. Scheme 2) and not a trace of the isotopomeric 2,3‐dihydro‐1,1,2,3‐tetramethyl‐1H‐[2‐¹³C]indene ( 5 ). The mechanism proposed in [3] for the cyclialkylation of 4 (cf. Scheme 2, Path A) has, therefore, to be abandoned. The mechanism of Scheme 2, Path B, is proposed and may be considered as definitively established.     

New Studies on [2+3] Cycloadditions of Thermally Generated N‐Isopropyl‐ and N‐(4‐Methoxyphenyl)‐Substituted Azomethine Ylides

The thermal reaction of 1‐substituted 2,3‐diphenylaziridines 2 with thiobenzophenone ( 6a ) and 9H‐fluorene‐9‐thione ( 6b ) led to the corresponding 1,3‐thiazolidines (Scheme 2). Whereas the cis‐disubstituted aziridines and 6a yielded only trans‐2,4,5,5‐tetraphenyl‐1,3‐thiazolidines of type 7 , the analogous reaction with 6b gave a mixture of trans‐ and cis‐2,4‐diphenyl‐1,3‐thiazolidines 7 and 8 . During chromatography on SiO₂, the trans‐configured spiro[9H‐fluorene‐9,5′‐[1,3]thiazolidines] 7c and 7d isomerized to the cis‐isomers. The substituent at N(1) of the aziridine influences the reaction rate significantly, i.e., the more sterically demanding the substituent the slower the reaction. The reaction of cis‐2,3‐diphenylaziridines 2 with dimethyl azodicarboxylate ( 9 ) and dimethyl acetylenedicarboxylate ( 11 ) gave the trans‐cycloadducts 10 and 12 , respectively (Schemes 3 and 4). In the latter case, a partial dehydrogenation led to the corresponding pyrroles. Two stereoisomeric cycloadducts, 15 and 16 , with a trans‐relationship of the Ph groups were obtained from the reaction with dimethyl fumarate ( 14 ; Scheme 5); with dimethyl maleate ( 17 ), the expected cycloadduct 18 together with the 2,3‐dihydropyrrole 19 was obtained (Scheme 6). The structures of the cycloadducts 7b, 8a, 15b , and 16b were established by X‐ray crystallography.     

Synthesis of [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine,and [1,2‐a] benzimidazol‐2‐yl amidrazone

N‐benzimidazol‐2‐yl imidate type 1 reacts with thiourea, carbon disulfide, cyanamide, and hydrazide to give, respectively, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione 2 , [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione 3 , [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine 4 , and [1,2‐a] benzimidazol‐2‐yl amidrazone 5 with good yields. Structures elucidation of all newly synthesized heterocyclic compounds was based on the data of IR, ¹H NMR, ¹³C NMR, elemental analysis, and MS of some products. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:279–283, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20618     

A Novel,One‐Pot Four‐Component Route to 2′‐Thioxo‐2′,3′‐dihydrospiro[indole‐3,6′‐[1,3]thiazin]‐2‐one Derivatives

An efficient route to 2′,3′‐dihydro‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives is described. It involves the reaction of isatine, 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one, and different amines in the presence of CS₂ in dry MeOH at reflux (Scheme 1). The alkyl carbamodithioate, which results from the addition of the amine to CS₂, is added to the α,β‐unsaturated ketone, resulting from the reaction between 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one and isatine, to produce the 3′‐alkyl‐2′,3′‐dihydro‐4′‐phenyl‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives in excellent yields (Scheme 2). Their structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses.     

A convenient synthesis of novel 7‐phosphonylbenzyl‐2‐substituted pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]‐pyrimidine derivatives

A series of pyrazolo[4,3‐e]‐1,2,4‐triazolo‐[1,5‐c]pyrimidine derivatives, bearing phosphonylbenzyl chain in position 7, were conveniently synthesized in an attempt to obtain potent and selective antagonists for the A_2A adenosine receptor or potent pesticide lead compounds. Diethyl[(5‐amino‐4‐cyano‐3‐methylsulfanyl‐pyrazol‐1‐yl)‐benzyl]phospho‐nate ( 3 ), which was prepared by the cyclization of diethyl 1‐hydrazinobenzylphosphonate ( 1 ) with 2‐[bis(methylthio)methylene]malononitrile ( 2 ), reacted with triethyl orthoformate to afford diethyl[(4‐cyano‐5‐ethoxymethyleneamino‐3‐methylsulfanyl‐pyrazol‐1‐yl)‐benzyl]phosphonate ( 4 ), which reacted with various acyl hydrazines in refluxing 2‐methoxyethanol to give the target compounds 5a–h in good yields. Their structures were confirmed by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. The crystal structure of 5e was determined by single crystal X‐ray diffraction © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:634–638, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20478     

Gold‐Catalyzed Intramolecular [3+2] Cycloadditions of 1‐Aryl‐1‐allene‐6‐enes

Treatment of 1‐aryl‐1‐allen‐6‐enes with [PPh₃AuCl]/AgSbF₆ (5 mol %) in CH₂Cl₂ at 25 °C led to intramolecular [3+2] cycloadditions, giving cis‐fused dihydrobenzo[a]fluorene products efficiently and selectively. The reactions proceeded with initial formation of trans/cis mixtures of 2‐alkyl‐1‐isopropyl‐2‐phenyl‐1,2‐dihydronaphthalene cations B, which were convertible into the desired cis‐fused cycloadducts through the combined action of a gold catalyst and a Brønsted acid. Theoretic calculation supports the participation of the trans‐B cation as reaction intermediate. Although HOTf showed similar activity towards several 1‐aryl‐1‐allen‐6‐enes, it lacks generality for this cycloaddition reaction.     

1,3‐Dipolar cycloadditions of (4R*,5R*)‐1‐alkylidene‐4‐(benzoylamino)‐5‐phenyl‐3‐pyrazolidinon‐1‐azomethine imines

1,3‐Dipolar cycloadditions of azomethine imines 3a and 3b , available by acid‐catalyzed treatment of 3‐pyrazolidinone 1 with acetone ( 2a ) and butyraldehyde ( 2b ), respectively, were studied. Reactions of 3a with DMAD ( 4 ) afforded a mixture of products 9 and 10a , whilst treatment of 3b with DMAD ( 4 ) gave a mixture of compound 9 and epimeric cycloadducts 10 / 10′b . On the other hand, cycloadducts 13a,b‐16a,b were isolated as single diastereomers in 9–37% yields upon reactions of 3a,b with olefinic dipolarophiles 5–8 . The structures of cycloadducts 9, 10a, 10/10′b , and 13a,b‐16a,b were determined by ¹H nmr and NOESY spectroscopy. The structure of compound 13a was confirmed by X‐ray diffraction.     

New domino‐reaction for the synthesis of N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines and 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine

The model morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) reacts with phenacyl bromides to afford N⁴‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines (4) or N⁴‐(4,5‐diphenyl‐1,3‐oxathiol‐2‐yliden)‐2‐phenyl‐4‐aminoquinazoline ( 5 ) by a thermodynamically controlled reversible reaction favoring the enolate intermediate, while the 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine ( 8 ) was produced by a kinetically controlled reaction favoring the C‐anion intermediate. ¹H nmr, ¹³C nmr, ir, mass spectroscopy and x‐ray identified compounds ( 4 ), ( 5 ) and ( 8 ).