Diastereoselective Alkyl Grignard 1,4‐Additions to para‐Substituted (2R)‐N‐Cinnamoylbornane‐10,2‐sultam Derivatives: Influence of N‐Atom Pyramidalization

Several typical ¹³C‐NMR displacements (of C?O, C(α), C(β), and C_ipso), as well as conformational or energy properties (S? N? C?O dihedral angle, ΔE syn/anti; HOMO/LUMO) could be correlated with the electronic parameters of p‐substituted N‐cinnamoylbornane‐10,2‐sultams 2 . Even under nonchelating conditions, the pyramidalization of the sultam N‐atom decreases for electron‐attracting p‐substituents, inducing a modification of the sultam‐ring puckering. Detailed comparison of the X‐ray structure analyses of 2b, 2d , and 2m showed that the orientation of the sterically directing pseudo‐axial S?O(2) and H? C(2) is modified and precludes any conclusion about the π‐facial stereoelectronic influence of the N lone pair on the alkyl Grignard 1,4‐addition. We also showed that the aggregating alkyl Grignard reagent may be used in equimolar fashion, demonstrating that the sultam moiety is chelated with a Lewis acid such as MgBr₂. The Schlenk equilibrium may also be used to generate the appropriate conditions of effective 1,4‐diastereoselectivity. Although the anti‐s‐cis/syn‐s‐cis difference of conformational energies for N‐cinnamoyl derivatives 2 is higher than for the simple N‐crotonoyl analogue, an X‐ray structure analysis of the SO₂/C?O syn derivative 10 confirms the predictive validity of our conformational calculations for ΔE≤1.8 kcal/mol.     

From Blue Azulenes to Blue Heptalenes – New Strongly Polarized π‐Convertible Heptalenes

The 1,5,6,8,10‐pentamethylheptalene‐4‐carboxaldehyde ( 4b ) (together with its double‐bond‐shifted (DBS) isomer 4a ) and methyl 4‐formyl‐1,6,8,10‐tetramethylheptalene‐5‐carboxylate ( 15b ) were synthesized (Schemes 3 and 7, resp.). Aminoethenylation of 4a / 4b with N,N‐dimethylformamide dimethyl acetal (=1,1‐dimethoxy‐N,N‐dimethylmethanamine=DMFDMA) led in DMF to 1‐[(1E)‐2‐(dimethylamino)ethenyl]‐5,6,8,10‐tetramethylheptalene‐2‐carboxaldehyde ( 18a ; Scheme 9), whereas the stronger aminoethenylation agent N,N,N′,N′,N″,N″‐hexamethylmethanetriamine (=tris(dimethylamino)methane=TDMAM) gave an almost 1 : 1 mixture of 18a and 1‐[(1E)‐2‐(dimethylamino)ethenyl]‐5,6,8,10‐tetramethylheptalene‐4‐carboxaldehyde ( 20b ; Scheme 11). Carboxylate 15b delivered with DMFDMA on heating in DMF the expected aminoethenylation product 19b (Scheme 10). The aminoethenylated heptalenecarboxaldehydes were treated with malononitrile in CH₂Cl₂ in the presence of TiCl₄/pyridine to yield the corresponding malononitrile derivatives 23b, 24b , and 26a (Schemes 13 and 14). The photochemically induced DBS process of the heptalenecarboxaldehydes as ‘soft’ merocyanines and their malononitrile derivatives as ‘strong’ merocyanines of almost zwitterionic nature were studied in detail (Figs. 10–29) with the result that 1,4‐donor/acceptor substituted heptalenes are cleaner switchable than 1,2‐donor/acceptor‐substituted heptalenes.     

Unexpected Reaction Course of 3‐Amino‐5‐aryl‐1H‐pyrazoles with Dialkyl Dicyanofumarates

On treatment of 3‐amino‐5‐aryl‐1H‐pyrazoles 1 with dialkyl dicyanofumarates (=(E)‐but‐2‐enedioates) 4 in boiling 1,2‐dichloroethane, two competitive reactions occurred leading to 3‐aryl‐5‐cyano‐6,7‐dihydro‐6‐oxo‐1H‐pyrazolo[3,4‐b]pyridine‐4‐carboxylates 10 and 7‐amino‐2‐arylpyrazolo[1,5‐a]pyrimidine‐5,6‐dicarboxylates 11 . In DMF at room temperature, as well as at 100°, only compounds 10 were isolated. The formation of the major products of type 10 was rationalized via Michael addition of 1 as a C(4)‐nucleophile onto 4 , followed by HCN elimination and lactamization. On the other hand, the minor products 11 result from a Michael addition of 1 onto 4 via the NH₂ group, and subsequent HCN elimination and cyclization. The structures of the products have been established by X‐ray crystallography.     

Two‐ and Three‐Component Reactions Leading to New Enamines Derived from 2,3‐Dicyanobut‐2‐enoates

The three‐component reactions of 1‐azabicyclo[1.1.0]butanes 1 , dicyanofumarates (E)‐ 5 , and MeOH or morpholine yielded azetidine enamines 8 and 9 with the cis‐orientation of the ester groups at the C?C bond ((E)‐configuration; Schemes 3 and 4). The structures of 8a and 9d were confirmed by X‐ray crystallography. The formation of the products is explained via the nucleophilic addition of 1 onto (E)‐ 5 , leading to a zwitterion of type 7 (Scheme 2), which is subsequently trapped by MeOH or morpholine ( 10a ), followed by elimination of HCN. Similarly, two‐component reactions between secondary amines 10a – 10c and (E)‐ 5 gave products 12 with an (E)‐enamine structure and (Z)‐oriented ester groups. On the other hand, two‐component reactions involving primary amines 10d – 10f or NH₃ led to the formation of the corresponding (Z)‐enamines, in which the (E)‐orientation of ester groups was established.     

X‐Ray Structure Study of an Unusual 13,14,15,16‐Tetranorlabdane Derivative Obtained in the Synthesis of (7α)‐7,8‐Dihydroxy‐14,15‐dinorlabdane‐11,13‐dione

The unconventional (5S,7R,8S,9R,10S)‐configurated (?)‐7‐(acetyloxy)‐12,12‐dichloro‐8‐hydroxy‐13,14,15,16‐tetranorlabdan‐11‐one ( 2 ) was synthesized via the HCl‐promoted hydrolysis of (7α)‐7,8‐(isopropylidenedioxy)‐14,15‐dinorlabdan‐11,13‐dione ( 5 ). Possible mechanistic pathways of the reaction are considered. Crystal and molecular structures of the isolated compound 2 were determined by single‐crystal X‐ray structure analysis.     

The Structures of Indazolin‐3‐one (=1,2‐Dihydro‐3H‐indazol‐3‐one) and 7‐Nitroindazolin‐3‐one

The existence of polymorphism in parent indazolin‐3‐one (=1,2‐dihydro‐3H‐indazol‐3‐one; 1 ) is reported as well as an X‐ray and NMR CPMAS study establishing that its 7‐nitro derivative 2 exists as the 3‐hydroxy tautomer. Absolute shieldings calculated at the GIAO/B3LYP/6‐311++G(d,p) level were used to determine the tautomeric oxo/hydroxy equilibrium in solution, i.e., always the 1H‐indazol‐3‐ol tautomer predominates.     

Synthesis and Crystal Structure of 3,3,6,6‐Tetramethylmorpholine‐2,5‐dione,and Its 5‐Monothioxo and 2,5‐Dithioxo Derivatives

The synthesis of 3,3‐dimethylmorpholine‐2,5‐diones 4a was achieved conveniently via the ‘direct amide cyclization’ of the linear precursors of type 3 , which were prepared by coupling of 2,2‐dimethyl‐2H‐azirin‐3‐amines 2 with 2‐hydroxyalkanoic acids 1 . Thionation of 4a with Lawesson's reagent yielded the corresponding 5‐thioxomorpholin‐2‐ones 10 and morpholine‐2,5‐dithiones 11 , respectively, depending on the reaction conditions. The structures of 3aa, 4aa, 10a , and 11a were established by X‐ray crystallography. All attempts to prepare S‐containing morpholine‐2,5‐dione analogs or thiomorpholine‐2,5‐diones by cyclization of corresponding S‐containing precursors were unsuccessful and led to various other products. The structures of some of them have also been established by X‐ray crystallography.     

A New Germanium Complex Containing Chelating Pyridinecarboxylate Ligands: cis‐Dihydroxybis(pyridine‐2‐carboxylato‐κN1,κO2)germanium Hydrate (1 : 2) (cis‐[Ge(pyca)2(OH)2]⋅2 H2O)

A new germanium complex, cis‐[Ge(pyca)₂(OH)₂]?2 H₂O ( 1 ; pyca=pyridine‐2‐carboxylato), was synthesized by the reaction of [Ge(acac)₂Cl₂] (acac=acetylacetonato=pentane‐2,4‐dionato) with potassium pyridine‐2‐carboxylate (Kpyca) in H₂O/THF. According to the single‐crystal X‐ray diffraction analysis, each Ge‐atom of 1 is coordinated by two pyca ligands and two OH^? groups (Fig. 1). These molecules are bonded to each other via a system of H‐bonds resulting in a sheet‐like structure (Fig. 2). The complex is decomposed during heating with stepwise mass loss and formation of GeO₂ as final product (Fig. 3).     

1,2‐Oxazine N‐Oxides as Catalyst Resting States in Michael Additions of Aldehydes to Nitro Olefins Organocatalyzed by α,α‐Diphenylprolinol Trimethylsilyl Ether

By combining enamines, derived from aldehydes and diphenylprolinol trimethylsilyl ether (the Hayashi catalyst), with nitroethenes ((D₆)benzene, 4‐Å molecular sieves, room temperature) intermediates of the corresponding catalytic Michael‐addition cycles were formed and characterized (IR, NMR, X‐ray analysis; Schemes 3–6 and Fig. 1–3). Besides cyclobutanes 2 , 1,2‐oxazine N‐oxide derivatives 3 – 6 and 8 have been identified for the first time, some of which are very stable compounds. It may not be a lack of reactivity (between the intermediate enamines and nitro olefins) that leads to failure of the catalytic reactions (Schemes 3–5) but the high stability of catalyst resting states. The central role zwitterions play in these processes is discussed (Schemes 1 and 2).     

Synthesis,Characterization, Crystal and Molecular Structure of 1,5‐Dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐imine

The reaction of 1,5‐dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐one ( 3 ) with an alkylamine (butylamine, hexylamine or ethylenediamine) yields, quite unexpectedly and in the absence of catalyst, the novel compound 1,5‐dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐imine ( 4 ) as the sole, analytically pure, solid product, which was fully characterized. The structure of 4 was unequivocally solved by single‐crystal X‐ray‐diffraction analysis. The compound crystallizes in a monoclinic cell (space group P 2₁/c), with two molecules in the asymmetric unit, held together by intermolecular H‐bonds. Compound 4 could be interesting as a bi‐ or even tridentate ligand, and exhibits a strong fluorescence upon excitation at 310 nm. A mechanism, based on the observed C? N bond cleavage, is proposed.     

Nitration Products of 5‐Amino‐1H‐tetrazole and Methyl‐5‐amino‐1H‐tetrazoles – Structures and Properties of Promising Energetic Materials

The nitration of 5‐amino‐1H‐tetrazole ( 1 ), 5‐amino‐1‐methyl‐1H‐tetrazole ( 3 ), and 5‐amino‐2‐methyl‐2H‐tetrazole ( 4 ) with HNO₃ (100%) was undertaken, and the corresponding products 5‐(nitrimino)‐1H‐tetrazole ( 2 ), 1‐methyl‐5‐(nitrimino)‐1H‐tetrazole ( 5 ), and 2‐methyl‐5‐(nitramino)‐2H‐tetrazole ( 6 ) were characterized comprehensively using vibrational (IR and Raman) spectroscopy, multinuclear (¹H, ¹³C, ¹⁴N, and ¹⁵N) NMR spectroscopy, mass spectrometry, and elemental analysis. The molecular structures in the crystalline state were determined by single‐crystal X‐ray diffraction. The thermodynamic properties and thermal behavior were investigated by using differential scanning calorimetry (DSC), and the heats of formation were determined by bomb calorimetric measurements. Compounds 2, 5 , and 6 were all found to be endothermic compounds. The thermal decompositions were investigated by gas‐phase IR spectroscopy as well as DSC experiments. The heats of explosion, the detonation pressures, and velocities were calculated with the software EXPLO5, whereby the calculated values are similar to those of common explosives such as TNT and RDX. In addition, the sensitivities were tested by BAM methods (drophammer and friction) and correlated to the calculated electrostatic potentials. The explosion performance of 5 was investigated by Koenen steel sleeve test, whereby a higher explosion power compared to RDX was reached. Finally, the long‐term stabilities at higher temperatures were tested by thermal safety calorimetry (FlexyTSC). X‐Ray crystallography of monoclinic 2 and 6 , and orthorhombic 5 was performed.     

Synthesis and Characterization of New Heptalenes with Extended π‐Systems Attached to Them

Methyl heptalenecarboxylates of type A and B with π(1) and π(2) substituents in 1,4‐relation (Scheme 1) were synthetized starting with dimethyl 1‐methylheptalene‐4,5‐dicarboxylates 5b and 6b derived from 7‐isopropyl‐1,4‐dimethylazulene (=guaiazulene) and 1,4,6,8‐tetramethylazulene by thermal reaction with dimethyl acetylenedicarboxylate. The further general way of proceeding for the introduction of the π(1) and π(2) substituents is displayed in Scheme 3, and the thus obtained methyl heptalene‐5‐carboxylates of type A and B are listed in Table 1. The C?C bonds of the 2‐arylethenyl and 4‐arylbuta‐1,3‐dien‐1‐yl groups of π(1) and π(2) were in all cases (E)‐configured and showed s‐trans conformation at the C? C bonds (X‐ray and ¹H‐NOE evidence) in the B ‐type as well as in the A ‐type heptalenes (cf. Figs. 5–12). All B ‐type heptalenes showed a strongly enhanced heptalene band I in the wavelength region 440–490 nm in hexane/CH₂Cl₂ 9 : 1 (cf. Table 4 and Figs. 13–20). The A ‐type heptalenes showed in this region only weak absorption, recognizable as shoulders or simply tailing of the dominating heptalene bands II/III (Table 5). Absorption band I of the B ‐type heptalenes appeared almost at the same wavelength as the longest wavelength absorption band of comparable open‐chain α,ω‐diarylpolyenes (cf. Fig. 21). The cyclic double bond shift (DBS) of the A ‐ and B ‐type heptalenes could be photochemically steered in one or the other direction by selective irradiation (cf. Fig. 22).     

Novel Synthesis of 2‐Alkylquinolizinium‐1‐olates and Their 1,3‐Dipolar Cycloaddition Reactions with Acetylenes

Several 2‐alkylquinolizinium‐1‐olates 9 , i.e., heterobetaines, were prepared from ketone 11 , the latter being readily available either from pyridine‐2‐carbaldehyde via a Grignard reaction, followed by oxidation with MnO₂, or from 2‐picolinic acid (=pyridine‐2‐carboxylic acid) via the corresponding Weinreb amide and subsequent Grignard reaction. Mesoionic heterobetaines such as quinolizinium derivatives have the potential to undergo cycloaddition reactions with double and triple bonds, e.g., 1,3‐dipolar cycloadditions or Diels? Alder reactions. We here report on the scope and limitations of cycloaddition reactions of 2‐alkylquinolizinium‐1‐olates 9 with electron‐poor acetylene derivatives. As main products of the reaction, 5‐oxopyrrolo[2,1,5‐de]quinolizines (=‘[2.3.3]cyclazin‐5‐ones’) 19 were formed via a regioselective [2+3] cycloaddition, and cyclohexadienone derivatives, formed via a Diels? Alder reaction, were obtained as side products. The structures of 2‐benzylquinolizinium‐1‐olate ( 9a ) and two ‘[2.3.3]cyclazin‐5‐ones’ 19i and 19l were established by X‐ray crystallography.     

Synthesis and Structure of O,O‐Diethyl N‐[(trans‐4‐Aryl‐5,5‐dimethyl‐2‐oxido‐2λ5‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates

A study on the synthesis of the novel N‐(cyclic phosphonate)‐substituted phosphoramidothioates, i.e., O,O‐diethyl N‐[(trans‐4‐aryl‐5,5‐dimethyl‐2‐oxido‐2λ⁵‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates 4a – l , from O,O‐diethyl phosphoramidothioate ( 1 ), a benzaldehyde or ketone 2 , and a 1,3,2‐dioxaphosphorinane 2‐oxide 3 was carried out (Scheme 1 and Table 1). Some of their stereoisomers were isolated, and their structure was established. The presence of acetyl chloride was essential for this reaction and accelerated the process of intramolecular dehydration of intermediate 5 forming the corresponding Schiff base 7 (Scheme 2).     

Synthesis of Macrocyclic Lactones via Ring Transformation of 4‐(ω‐Hydroxyalkyl)‐1,3‐oxazol‐5(4H)‐ones

The synthesis of α‐benzamido‐α‐benzyl lactones 23 of various ring size was achieved either via ‘direct amide cyclization’ by treatment of 2‐benzamido‐2‐benzyl‐ω‐hydroxy‐N,N‐dimethylalkanamides 21 in toluene at 90 – 110° with HCl gas or by ‘ring transformation’ of 4‐benzyl‐4‐(ω‐hydroxyalkyl)‐2‐phenyl‐1,3‐oxazol‐5(4H)‐ones under the same conditions. The precursors were obtained by C‐alkylations of 4‐benzyl‐2‐phenyl‐1,3‐oxazol‐5(4H)‐one ( 15 ) with THP‐ or TBDMS‐protected ω‐hydroxyalkyl iodides. Ring opening of the THP‐protected oxazolones by treatment with Me₂NH followed by deprotection of the OH group gave the diamides 21 , whereas deprotection of the TBDMS series of oxazolones 25 with TBAF followed by treatment with HCl gas led to the corresponding lactones 23 in a one‐pot reaction.     

New Aspects of 1,3‐Diphosphacyclobutane‐2,4‐diyls

1,3‐Di(tert‐butyl)‐2,4‐bis[2,4,6‐tri(tert‐butyl)phenyl]‐1,3‐diphosphacyclobutane‐2,4‐diyl was formed from [2,4,6‐tri(tert‐butyl)phenyl]phosphaacetylene and t‐BuLi. In addition, the X‐ray diffraction analysis was carried out, together with theoretical calculations of the structure and NMR data.     

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.     

New Selenosemicarbazides Derived from Imidazole‐Based Carbohydrazides

Imidazole‐based carbohydrazides, i.e., 3‐oxidoimidazole‐4‐carbohydrazides 1 and 2‐[(imidazol‐2‐yl)sulfanyl]acetohydrazides 6 , react with aryl isoselenocyanates 4 in MeOH at room temperature to give the corresponding selenosemicarbazides 5 and 7 , respectively, in good yields. On heating 7b in DMF in the presence of air to 100°, 1,3,4‐oxadiazole 8a was formed via cyclization and formal elimination of H₂Se. Product 8a was also obtained after heating of a mixture of 4a and 6b under the same conditions. On the other hand, on heating of a solution of 7c in MeOH at reflux, a cyclization occurred to give the corresponding 1,2,4‐triazole‐3‐selone 9b . Again, the same product was formed when a mixture of 4b and 6b was heated in MeOH. Surprisingly, analogous cyclizations of selenosemicarbazides of type 5 under the same conditions failed, and only decomposition was observed. The structures of 7a, 7d , and 9b have been established by X‐ray crystallography.     

Formation of Dimers of Some 2‐Substituted Indan‐1‐one Derivatives during Base‐Mediated Cross‐Aldol Condensation

Unexpected dimers of some 2‐substituted indan‐1‐one derivatives were isolated during aldol condensation of indan‐1‐one with various aldehydes in the presence of KOH (see Scheme). Monomeric products, usually expected from aldol condensation, further underwent a base‐catalyzed nucleophilic addition reaction to their dimeric form in some cases. The structures of these dimers were characterized by using various spectral techniques and in one case, structural details were determined from a high‐resolution crystallographic analysis.     

Spectroscopic,Thermal, and Structural Studies of Two New Co‐Crystals of [4,4′‐Bithiazole]‐2,2′‐diamine

Two new 2 : 1 co‐crystals based on [4,4′‐bithiazole]‐2,2′‐diamine (=2,2′‐diamino‐4,4′‐bithiazole (DABTZ)) with 2,2′‐bipyridine (bipy) and benzo‐18‐crown‐6 (bk) were synthesized by slow‐evaporation method in MeOH. These co‐crystals were characterized by means of elemental analysis, and IR, and ¹H‐ and ¹³C‐NMR spectroscopy. Also, thermal analyses under air atmosphere and X‐ray crystallography have been performed on these structures. X‐Ray single‐crystal analyses revealed that these networks contain large vacant voids. These structures, [(DABTZ)₂(bipy)] and [(DABTZ)₂(bk)(MeOH)], crystallized in monoclinic and triclinic forms with space groups of P2₁/c and P , respectively. The self‐assembly of these compounds in the solid state is likely caused by both H‐bonding and π? π stacking.