Zn-promoted regio- and sequence-selective one-pot joining reactions of three components: vinylpyridines, alkyl iodides, and carbonyl compounds (or nitriles)

Addition of alkyl iodides (3) into the solution containing 2-(or 4-)vinylpyridine (1 or 2) and carbonyl compounds (6) in the presence of Zn-powder (99.9%) in acetonitrile under refluxing brought about regio- and sequence-selective joining reaction of three components to give the corresponding (2-hydroxyethyl)pyridines (7 or 8) in good to moderate yields. On the other hand, 2-(2- or 4-pyridyl)ethyl alkyl ketones (10 or 11) were obtained from the similar joining reaction of three components by addition of alkyl iodides (3) into the solution of 2-(or 4-)vinylpyridine (1 or 2), and nitriles (9) in toluene containing Zn-powder (99.9%) under the similar reaction conditions.     

Amphiphilic perfluoroalkylated sulfones and sulfonate betaines

Two types of perfluoro alkyl-containing amphiphilic sulfones 7-9 and 13-15, respectively, and sulfonate betaines 23-32 were prepared using 2-[(perfluoroalkyl)methyl]oxiranes (1-3, R_F = C₄F₉, C₆F₁₃, C₈F₁₇) or 3-(perfluoroalkyl)propyl iodides (16 and 17, R_F = C₆F₁₃, C₈F₁₇) as the starting compounds. The overall yields of two-step syntheses were above 90%. The compounds 7-9 were prepared by the reaction of oxiranes 1-3 with 2-sulfanylethan-l-ol and subsequent oxidation of intermediate sulfides. Similarly, the amphiphiles 13-15 were obtained by analogous reaction of oxiranes 1-3 with thiomorpholine and subsequent oxidation of the sulfur atom in the morpholine ring. In the syntheses of betaines 23-32, the starting compounds 1-3 or 16 and 17 were first reacted with dimethylamine followed by the ring-opening reaction of the intermediate fluoroalkyl(dimethyl)amines with propane-1,3- or butane-1,4-sultones.     

Reactions of guaiazulene with methyl terephthalaldehydate and 2-hydroxy- and 4-hydroxybenzaldehydes in methanol in the presence of hexafluorophosphoric acid: comparative studies on molecular structures and spectroscopic, chemical and electrochemical properties of monocarbocations stabilized by 3-guaiazulenyl and phenyl groups

Reaction of guaiazulene (1) with methyl terephthalaldehydate (2) in methanol in the presence of hexafluorophosphoric acid at 25 °C for 2 h under aerobic conditions gives (3-guaiazulenyl)[4-(methoxycarbonyl)phenyl]methylium hexafluorophosphate (5) in 94% yield. Similarly, reactions of 1 with 2-hydroxybenzaldehyde (3) and 4-hydroxybenzaldehyde (4) under the same reaction conditions as 2 give (3-guaiazulenyl)(2-hydroxyphenyl)methylium hexafluorophosphate (6) and (3-guaiazulenyl)(4-hydroxyphenyl)methylium hexafluorophosphate (7) in 89 and 97% yields, respectively. Comparative studies on the molecular structures as well as the spectroscopic, chemical and electrochemical properties of the monocarbocation compounds 5-7 stabilized by 3-guaiazulenyl and 4-(methoxycarbonyl)phenyl (or 2-hydroxy- or 4-hydroxyphenyl) groups are reported.     

Structurally original oxathioethers macrocycles containing an exocyclic double-bond: synthesis,characterization, reactivity,and coordination

New oxathioethers macrocycles have been synthesized and characterized. Each macrocycle consists in structurally defined ether and thioether moieties and an exocyclic double-bond (2a–c) or a hydroxymethyl group (3a–c). Macrocycles (2a–c) have been synthesized by reaction of dianions of thioethers diols (1a–c) with 3-chloro-2-chloromethylprop-1-ene. Their hydroboration/oxidation led to corresponding primary alcohols (3a–c). Structures of compounds (2b) and (3a) have been determined by X-ray diffraction. The reactivity of the hydroxyl group allowed the preparation of oxathioethers macrocycles bearing a polyether chain or a benzyl group (4a,b) and the synthesis of new bicyclic sandwich-type compounds (5a,b). The ability of these functionalized macrocycles to coordinate to palladium has been investigated.     

From bis(silylamino)tin dichlorides via di(1-alkynyl)-bis(silylamino)tin to new heterocycles by 1,1-organoboration

Bis(silylamino)tin dichlorides 1 [X₂SnCl₂ with X=N(Me₃Si)₂ (a), N(9-BBN)SiMe₃ (b), N(^tBu)SiMe₃ (c), and N(SiMe₂CH₂)₂ (d)] were prepared from the reaction of two equivalents of the respective lithium amides (Li-a-d) with tin tetrachloride, SnCl₄, or from the 1:1 reaction of the respective bis(amino)stannylene with SnCl₄. The compounds 1 react with two equivalents of lithium alkynides LiCCR¹ to give the di(1-alkynyl)-bis(silylamino)tin compounds X₂Sn(CCR¹)₂, 2 (R¹=Me), 3 (R¹=^tBu), and 4 (R¹=SiMe₃). Problems were encountered, mainly with LiCC^tBu as well as with 1b, since side reactions also led to the formation of 1-alkynyl-bis(silylamino)tin chlorides 5-7 and tri(1-alkynyl)(silylamino)tin compounds 8 and 9. 1,1-Ethylboration of compounds 2-4 led to stannoles 10, 11, and in the case of propynides, also to 1,4-stannabora-2,5-cyclohexadiene derivatives 12. The molecular structure of the stannole 11b (R¹=SiMe₃) was determined by X-ray analysis. The reaction of 2a and d with triallylborane afforded novel heterocycles, the 1,3-stannabora-2-ethylidene-4-cyclopentenes 14. These reactions proceed via intermolecular 1,1-allylboration, followed by an intramolecular 1,2-allylboration to give 14, and a second intramolecular 1,2-allylboration leads to the bicyclic compounds 15.     

An efficient preparation, crystal structures, and properties of monocarbenium-ion compounds stabilized by 3-guaiazulenyl and anisyl groups

Reaction of guaiazulene (1) with 2-methoxybenzaldehyde (2) in methanol in the presence of hexafluorophosphoric acid at 25 °C for 2 h gives (3-guaiazulenyl)(2-methoxyphenyl)methylium hexafluorophosphate (5a) in 93% yield. Similarly, reaction of 1 with 3-methoxybenzaldehyde (3) or 4-methoxybenzaldehyde (4) under the same reaction conditions as for 2 affords (3-guaiazulenyl)(3-methoxyphenyl)methylium hexafluorophosphate (6) (91% yield) or (3-guaiazulenyl)(4-methoxyphenyl)methylium hexafluorophosphate (7) (97% yield). The crystal structures as well as the spectroscopic, electrochemical, and chemical properties of these monocarbenium-ion compounds, possessing interesting resonance forms, stabilized by the 3-guaiazulenyl and anisyl (i.e., 2-, 3-, or 4-methoxyphenyl) groups are reported.     

Unexpected fragmentation of phenyldithiobenzoate, formation and X-ray structure of [μ,η(S,S)-1,2-(dithio)-1,2-(diphenylethylene)] diiron hexacarbonyl complex

The reaction of Fe₂(CO)₉ with phenyldithiobenzoate PhCS₂Ph 1 afforded four colored compounds: [(μ-η³(C,S,S)PhCS₂Ph)]Fe₂(CO)₆2, (μ-S)₂Fe₃(CO)₉3, (μ-SPh)₂Fe₂(CO)₆4 and [μ-η²(S,S)][PhC(S)C(S)Ph]Fe₂(CO)₆5. Complex 5 was characterized by X-ray crystallography. The formation of complexes 4 and 5 was unexpected since it involved a fragmentation of the organic ligand 1 during its reaction with Fe₂(CO)₉. The electrochemical studies of 1, complexes 2 and 3 were undertaken in order to get information about the chemical behaviors of the intermediates generated by electron transfer. The results of cyclic voltammetry studies of 2 and 1 suggested that the reaction of 1 with Fe₂(CO)₉ involved two competitive reactions: (i) a thermal reaction which led to the expected compounds 2 and 3 and (ii) an electron transfer reaction involving a fragmentation of starting ligand 1 led to the unexpected complex 5. The required electrons may be provided by iron during the thermal decay of complexes 2 or 3 or Fe₂(CO)₉.     

Synthesis and photochromic behaviour of new methyl induced linear and angular thieno-2H-chromenes

New methyl induced linear and angular thieno-2H-chromenes 4, 5 and 6 were prepared by reaction of new methylated 6-hydroxybenzo[b]thiophenes 2 (a, b and c) and propargylic alcohols 3a and 3b, using acidic Alumina Brockmann I as catalyst and drying agent. Compounds 2 were prepared in good to excellent yields in a ‘one pot’ three step reaction from the corresponding bromo compounds 1. The photochromic behaviour of compounds 4, 5 and 6b was evaluated with the aid of a classical set of spectrokinetic parameters, and compared to reference compounds that are benzoannellated in the 5,6 and 6,7 positions of the chromene (naphthopyrans) and also to thieno-2H-chromenes 7 and 8, previously prepared, which are analogues of 5a. The resistance to fatigue (photodegradation) under continuous irradiation was also evaluated.     

Syntheses and coordination chemistry of methylpyridylphosphine oxide ligands with copper(II)

The coordination properties of three heterofunctional phosphine oxide ligands, 2-methylpyridyldiphenylphosphine oxide (L1), phenylphosphino-bis-2-methylpyridine oxide (L2) and phenylphosphino-bis-2-methylpyridine N,N′,P-trioxide (L3) with Cu(II) is described. The X-ray crystal structures of the compounds display a distorted octahedral geometry, which exhibit Jahn–Teller distortions. In compounds 1 and 2, the L1 and L2 ligands react with Cu(BF₄)₂ in a 2:1 ligand to metal ratio, respectively, with the BF₄ anions interacting with the metal center. L3 reacts with Cu(BF₄)₂ in 1:1 and 2:1 ligand/metal ratios to form compounds 3 and 4, respectively. Addition of either 2,2′-bipyridine or 4,4′-bipyridine to reaction solutions containing Cu(BF₄)₂ and L3 produces a discrete molecule (5) and a polymeric structure (7), respectively. The reaction of both bipyridines in the presence of Cu(BF₄)₂ and L3 gives rise to a discrete molecule (6) characterized by two octahedral coppers interconnected by the 4,4′-bipyridine. The electrochemical and photophysical properties of all compounds were investigated by cyclic voltammetry (CV) and UV–Vis, as they exhibited no emission or excitation in fluorimetric experiments.     

A practical one-pot procedure for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinones by a tandem aza-Wittig/heterocumulene-mediated annulation strategy

A simple one-pot and efficient method is described for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinone derivatives 6 via a tandem aza-Wittig/heterocumulene-mediated annulation process. The iminophosphorane 3 reacted with aryl isocyanates, followed by heterocyclization on addition of secondary amines to give the corresponding guanidine intermediates 5, which were cyclized in the presence of a catalytic amount of potassium carbonate to tricyclic compounds 6. Similarly, iminophosphorane 3 reacts with phenols, thiophenol, or ROH to give 2-aryl(alkyl)oxy(thio)pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinone derivatives 7 in good yields. The corresponding carbodiimide 4c and guanidine-type intermediate compounds 5 could be isolated and characterized, thus confirming the suggested reaction pathway. However, two isomeric pyrazinothienopyrimidinones 8 and 9 may be produced in the reaction of iminophosphorane 3 with aromatic isocyanates and subsequent reaction with primary amines in the presence of a catalytic amount of potassium carbonate. The effects of the nucleophiles and isocyanates on the regioselectivity of the cyclization have been investigated.     

Regioselective synthesis of 2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-ones by the cyclization of 3-acyl-4-methoxy-1-methylquinolinones with hydrazines

Reaction of 3-acyl-4-methoxy-1-methylquinolinones 2 and 5 with hydrazines has been investigated under different experimental conditions. Compound 2 always gave rise selectively and exclusively to the regioisomeric 1,3-disubstituted- or 2,3-disubstituted-pyrazolo[4,3-c]quinolin-4(5H)one (compounds 3a,b or 4a,b, respectively), while reaction of 5 with N-methylhydrazine led to a mixture of pyrazoles 7a and 8a. With N-phenylhydrazine, compounds 7b or 8b were regioselectively obtained. Compound 8a could be selectively synthesized working in solventless conditions. Structural elucidation of all products was independently achieved by NMR spectroscopy.     

Synthesis, IR-, NMR- and X-ray investigations on some novel N-hetaryl-dihydro-pyrazolyl ferrocenes. Study on ferrocenes, part 16

Cyclocondensation of 1-aryl-3-ferrocenyl-2-propen-1-ones (1) with hetaryl hydrazines resulted in N-hetaryl-3-aryl-5-ferrocenyl pyrazolines (3, 4). The analogous 3-aryl-1-ferrocenyl-2-propen-1-ones (5) gave the isomeric N-hetaryl-5-aryl-3-ferrocenyl-pyrazolines (6, 10), but in lower yield. The reaction of aryl-chalcones (7) with 4-hydrazino-phthalazinone led to 3,5-bis-aryl-N-hetaryl-pyrazolines (8) or to the corresponding ene-hydrazones (9). The structure of the new compounds was established by IR, ¹H and ¹³C NMR spectroscopy, including DNOE, HMQC, HMBC and DEPT methods. For compounds 1b, 3b and 8b the stereo structure was elucidated also by X-ray diffraction.     

Synthesis of polyfunctionalized furans from 3-acetyl-1-aryl-2-pentene-1,4-diones

The BF₃-catalyzed cyclization of 3-acetyl-1-aryl-2-pentene-1,4-diones 1a-e in the presence of water in boiling tetrahydrofuran gave bis(3-acetyl-5-aryl-2-furyl)methanes 2a-e in 26-79% yields along with a small amount of 3-acetyl-5-aryl-2-methylfurans 3a-e. The exact structure of 2a was determined by X-ray crystallography. The use of a half volume of the solvent for the reaction of 1a resulted in the formation of 2,4-bis(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-phenylfuran (4) together with 2a and 3a. A similar reaction of 1a was carried out in the presence of 3-acetyl-5-(4-methylphenyl)-2-methylfuran (3d) to afford 4-(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-(4-methylphenyl)-2-methylfuran (5) in 49% yield. The BF₃-catalyzed reaction of 1a with 2,4-pentanedione in dry tetrahydrofuran at 23°C gave 3-(3-acetyl-5-phenyl-2-furfuryl)-4-hydroxy-3-penten-2-one (6a) and 3-(3-acetyl-2-methyl-4-phenyl-5-furyl)-4-hydroxy-3-penten-2-one (7a) in 66 and 24% yields, respectively. The product distribution depended on the reaction temperature. A similar reaction of 1b-e also yielded the corresponding trisubstituted furans 6b-e and tetrasubstituted furans 7b-e in good yields. These results suggested the presence of the furfuryl carbocation intermediate A during the reaction. The one-pot synthesis of 6a and 7a was also achieved by a similar reaction using phenylglyoxal. The deoxygenation of 1a with triphenylphosphine gave 3a in 88% yield, while 1a was treated with concentrated hydrochloric acid to yield 3-acetyl-2-chloromethyl-5-phenylfuran (8) which was quantitatively transformed in ethanol into 3-acetyl-2-ethoxymethyl-5-phenylfuran (9) and in water into 3-acetyl-5-phenylfurfuryl alcohol (10), respectively. In addition, the Diels-Alder reaction of cyclopantadiene with 1a gave the corresponding [4+2] cycloaddition products 11 and 12.     

Synthesis and structure of 8-hydroxy-6-methoxy-3,7-dimethylisochromane and its analogues

The title compound 1 was obtained by the reaction of alcohol 18 and triethyl orthoformate catalyzed by aluminum chloride followed by catalytic hydrogenation in good yield. Similarly, compounds 1 and 3 were obtained by intramolecular cyclization of MOM ether 19 with titanium(IV) chloride in moderate yields and isochromanes 1, 3, 26 and 27 by intramolecular cyclization of ether 20 with titanium(IV) chloride in high yields. The structures of compounds 1-3 were elucidated by analysis of spectroscopic data and chemical reactions. The mechanisms on the formation of 1 and 3 are discussed.     

Quantum chemical study of ethylene addition to group-7 oxo complexes MO2(CH3)(CH2) (M = Mn, Tc, Re)

Quantum chemical calculations using DFT at the B3LYP level have been carried out for the reaction of ethylene with the group-7 compounds ReO₂(CH₃)(CH₂) (Re1), TcO₂(CH₃)(CH₂) (Tc1) and MnO₂(CH₃)(CH₂) (Mn1). The calculations suggest rather complex scenarios with numerous pathways, where the initial compounds Re1-Mn1 may either engage in cycloaddition reactions or numerous addition reactions with concomitant hydrogen migration. There are also energetically low-lying rearrangements of the starting compounds to isomers which may react with ethylene yielding further products. The [2 + 2]_Re,C cycloaddition reaction of the starting molecule Re1 is kinetically and thermodynamically favored over the [3 + 2]_C,O and [3 + 2]_O,O cycloadditions. However, the reaction which leads to the most stable product takes place with initial rearrangement to the dioxohydridometallacyclopropane isomer Re1a that adds ethylene with concomitant hydrogen migration yielding Re1a-1. The latter reaction has a slightly higher barrier than the [2 + 2]_Re,C cycloaddition reaction. The direct [3 + 2]_C,O cycloaddition becomes more favorable than the [2 + 2]_M,C reaction for the starting compounds Tc1 and Mn1 of the lighter metals technetium and manganese but the calculations predict that other reactions are kinetically and thermodynamically more favorable than the cycloadditions. The reactions with the lowest activation barriers lead after rearrangement to the ethyl substituted dioxometallacyclopropanes Tc1a-1 and Mn1a-1. The manganese compound exhibits an even more complex reaction scenario than the technetium compounds. The thermodynamically most stable final product of ethylene addition to Mn1 is the ethoxy substituted metallacyclopropane Mn1a-2 which has, however, a high activation barrier.     

Synthesis of fluorine containing glycolurils and oxazolines from oxides of internal perfluoroolefins

The reaction of oxides of internal perfluoroolefins 1-3 with urea gave two kinds of novel fluorine containing N-heterocyclic compounds depending on the solvent nature: 1,5-bis(perfluoroalkyl)tetraazabicyclo[3.3.0]octane-3,7-diones 4a-c and 2-amino-5-fluoro-4,5-bis(perfluoroalkyl)-4,5-dihydrooxazol-4-ols 7a-d. Use of polar dimethylsulfoxide, N,N-dimethylacetamide and acetonitrile afforded glycolurils 4a-c in moderate yields. In dioxane, unexpected cyclization occurred resulting in oxazolines 7a-d in high yields. A similar reaction of oxiranes 2, 3 with urea in aqueous dioxane gave mixtures of 4,5-dihydroxy-4,5-bis(perfluoroalkyl)imidazolidine-2-ones 9b, c, glycolurils 4b, c and oxazolines 7b-d. The molecular structure of trans-isomers of oxazoline 7b and imidazolidine 9b has been established by X-ray crystallography.     

Study on the reactions of ethyl 4,4,4-trifluoro-3-oxobutanoate with arylidenemalononitriles

In the presence of a catalytic amount of NEt₃, ethyl 4,4,4-trifluoro-3-oxobutanoate 1 reacted readily with arylidenemalononitriles 2 in ethanol at room temperature. It gave two products 2-trifluoromethyl-3,4-dihydro-2H-pyran derivatives 3 and 2-(trifluoromethyl)piperidine derivatives 4, the ratio of 3 and 4 was depended on the substrates 2 and reaction solvents. Reflux of the ethanol solution of 4 with a catalytic amount of NEt₃ afforded 2-trifluoromethyl-1,4,5,6-tetrahydropyridine derivatives 5 in moderate to good yields. The structures of new compounds 3, 4 and 5 were determined by spectral methods, microanalysis and X-ray diffraction analysis. A possible reaction mechanism for the formation of 3, 4 and 5 was presented.     

Synthesis of acyclic nucleoside analogues based on 1,2,4-triazolo[1,5-a]pyrimidin-7-ones by one-step Vorbrüggen glycosylation

New acyclovir analogues were obtained by reaction of 1,2,4-triazolo[1,5-a]pyrimidin-7-ones 4a–i with (2-acetoxyethoxy)methyl acetate 5 in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as catalyst (Vorbrüggen procedure). Coupling between compounds 4a–f and 5 led to a mixture of N3- and N4-isomers 6 and 7, respectively. On the contrary, the reaction of compounds 4g–i with 5 proceeded selectively with formation of N3-isomers only. It was found that the ratio of 6a–f and 7a–f depends on the presence or the absence of N,O-bis(trimethylsilyl)acetamide (BSA). Glycosylated products 6a–f and 7a–f underwent reversible isomerization under TMSOTf treatment. The ratio of glycosylated products of the coupling reaction between 4 and 5 was thermodynamically controlled. A similar reaction occurred if ZnCl₂ was chosen as a catalyst, although lower yields of the acyclic analogues of nucleosides were observed. The glycosylation of other purines (adenine and guanine) can be achieved via the non-BSA modification of the Vorbrüggen procedure.     

Efficient and regioselective chromium(0)-catalyzed reaction of 2-substituted furans with diazo compounds: stereoselective synthesis of (2E,4Z)-2-aryl-hexadienedioic acid diesters

Pentacarbonyl(η²-cis-cyclooctene)chromium(0) (1) catalyzes efficiently reactions of diazo compounds with electron-rich furans. The reaction of 2-methoxyfuran (2) with alkyl α-diazoarylacetate (3a-g) furnishes the (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g) in excellent yields. These reactions are highly regioselective. The cyclopropanation intermediates formed from 1 and diazo compounds 3a-g always arise from a carbene addition to the less substituted CC bond of 2. The resulting cyclopropanation product undergoes a ring opening reaction to form the corresponding (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g). The pentacarbonylchromium(0)-catalyzed reactions of 2-alkylfuran (5a-b) with ethyl α-diazophenylacetate (3a) and 9-diazo-9H-fluorene (3h) produce the 1(E),3(E)-butadienes (6a-d) in very good yields.     

Synthesis and properties of 3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and related compounds: photo-induced autorecycling oxidation of some amines

Novel 3-phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and the corresponding imino derivatives 5a,b and 6a,b were synthesized in modest to moderate yields by the abnormal and normal aza-Wittig reaction of 2-(1,3-diazaazulen-2-ylimino)triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. The related cationic compound, 1-methyl-3-phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate 7a, was also prepared. The electrochemical reduction of these compounds exhibited more positive reduction potentials as compared with those of the related compounds of 3,10-disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione systems. In a search of the oxidizing ability, compounds 5a, 6a, and 7a were demonstrated to oxidize some amines to give the corresponding imines in more than 100% yield under aerobic and photo-irradiation conditions, while even benzylamine was not oxidized under aerobic and thermal conditions at 100 °C. The oxidation reactions by cation 7a are more efficient than that by 5a and 6a. Quenching of the fluorescence of 5a was observed, and thus, the oxidation reaction by 5a probably proceeds via electron-transfer from amine to the excited singlet state of 5a. In the case of cation 7a, the oxidation reaction is proposed to proceed via formation of an amine-adduct of 7a and subsequent photo-induced radical cleavage reaction.