Studies in fluorinated 1,3-diketones and related compounds Part XII. Synthesis and spectroscopic studies of some new polyfluorinated 1,3-diketones,and their copper 1,3-diketonates

New polyfluorinated 1,3-diketones have been prepared from polyfluorinated acetophenones and appropriate esters in the presence of sodamide. The corresponding copper 1,3-diketonates have been obtained by treating a methanolic solution of polyfluorinated 1,3-diketone with methanolic solution of copper acetate. The polyfluorinated 1,3-diketones have been characterized by elemental as well as by spectral studies, viz: I.R., ¹H N.M.R. and ¹⁹F N.M.R. In I.R., characteristic absorptions observed are: CF stretching bands (1300 ? 1000) cm^?1, CF deformation modes (900 ? 700 cm^?1) and intramolecular hydrogen bonding (3000 ? 2500 cm^?1). In ¹H N.M.R. methine ( = C$\text{H}$) signal is observed at δ 6.2 ? 6.8 ppm and enolic proton resonance signal at δ 13 ? 15 ppm indicating the presence of strong hydrogen bonding in such polyfluorinated 1,3-diketones.     

Diastereoselective cycloadditions of 1,3-thiazolium-4-olates with chiral 1,2-diaza-1,3-butadienes

A series of 2-(N-methyl)benzylamino-1,3-thiazolium-4-olates (2-aminothioisomunchnones) react with chiral 1,2-diaza-1,3-butadienes derived from carbohydrates to afford a diastereomeric mixture of (4R,5S)- and (4R,5R)-4,5-dihydrothiophenes. These substrate-controlled cycloadditions are chemoselective, regiospecific, and proceed with a high facial diastereoselection. A theoretical rationale at semiempirical level does justify the stereochemical outcome observed in the experiments.     

Hydrothiolysis of 1,3-dihalopropan-2-ones

Acid-catclyzed hydrothiolysis of 1,3-dihaloacetones (XCH₂)₂CO (X=Cl, Br) at low temperature was investigated in various solvents. Optimum conditions were found for the formation of 1,3-dichloropropan-2-ol-2-thiol and 1,3-dibromo(dichloro)propan-2-thiones, the first representatives of compounds containing (XRR′C)₂C(OH)SH and (XRR′C)₂C=S (X=Hlg, R,R′=H, hydrocarbyl) fragments.     

Enzymatic resolution, desymmetrization, and dynamic kinetic asymmetric transformation of 1,3-cycloalkanediols

An efficient desymmetrization of cis-1,3-cyclohexanediol to (1S,3R)-3-(acetoxy)-1-cyclohexanol ((R,S)-2a) was performed via Candida antarctica lipase B (CALB)-catalyzed transesterification, in high yield (up to 93%) and excellent enantioselectivity (ee's up to >99.5%). (R,R)-Diacetate ((R,R)-3a) was obtained in a DYKAT process at room temperature from (1S,3R)-3-acetoxy-1-cyclohexanol ((R,S)-2a), in a high trans/cis ratio (91:9) and in excellent enantioselectivity of >99%. Metal- and enzyme-catalyzed dynamic transformation of cis/trans-1,3-cyclohexanediol using PS-C gave a high diastereoselectivity for cis-diacetate (cis/trans = 97:3). The (1R,3S)-3-acetoxy-1-cyclohexanol (ent-(R,S)-2a) was obtained from cis-diacetate by CALB-catalyzed hydrolysis in an excellent yield (97%) and selectivity (>99% ee). By deuterium labeling it was shown that intramolecular acyl migration does not occur in the transformation of cis-monoacetate to the cis-diacetate.     

New synthesis, properties, and oxidizing ability of 1,3-dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidin- 2,4(1,3H)-dionylium tetrafluoroborate

A novel synthesis of 1,3-dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)-dionylium tetrafluoroborate (10(+).BF(4)(-)) was accomplished by the reaction of 3,8-methano[11]annulenone with dimethylbarbituric acid and following acidic cyclization, albeit in low yield. Remarkable structural characteristics were suggested on inspection of the spectral data and MO calculation, and it was clarified that the positive charge is largely localized at the C11. The pK(R+) value of cation 10(+) was determined spectrophotometrically to be 4.6, which is much smaller by 4.1 pH unit than that of 1,3-dimethyl-7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)-dionylium tetrafluoroborate (pK(R+) = 8.7). This value is also smaller by 1.6 pH unit than that of the parent 1,6-methano[11]annulenylium ion (pK(R+) = 6.2). The feature is rationalized on the basis of the perturbation derived from the bond fixation of the parent cation. The electrochemical reduction of 10(+) exhibited less negative reduction potential at -0.39 (V vs Ag/AgNO(3)) upon cyclic voltammetry (CV). In a search for reactivity, reactions of 10(+) with some nucleophiles, hydride and diethylamine, were carried out to give mixtures of C11- and C13-adducts. In both reactions, the methano-bridge controls the nucleophilic attacks to the C13 to favor exo selectivity. The photoinduced autorecycling oxidation reactions of 10(+).BF(4)(-) toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) in 719-3286% yield (recycling number of 10(+).BF(4)(-): 7.2-32.9).     

Synthesis of 1,3-dithianes and 1,3-dithiolanes. Baker's yeast reduction and lipase-catalyzed resolution for synthesis of enantiopure derivatives.

Three 1,3-dithiolanes and four 1,3-dithianes have been synthesised from 1-(1,3-dithiolan-2-yl)-2-propanone and 1-(1,3-dithian-2-yl)-2-propanone, respectively. Asymmetric reductions of these ketones using baker's yeast gave the corresponding enantiopure (S)-alcohols. Baker's yeast also reduced the double bond in 3-(1,3-dithian-2-yl)-3-buten-2-one enantioselectively to give (S)-3-(1,3-dithian-2-yl)-2-butanone. 3-(1,3-Dithian-2-yl)-3-buten-2-one was also reduced chemo-selectively and the resulting 3-(1,3-dithian-2-yl)-3-buten-2-ol was resolved by transesterification in organic solvent using lipase B from Candida antarctica to yield the (S)-alcohol and the (R)-acetate with very high enantiomeric ratio, E. Racemic 1-(1,3-dithiolan-2-yl)-2-propanol and 1-(1,3-dithian-2-yl)-2-propanol were also resolved under similar conditions to give the (S)-alcohols and the corresponding (R)-acetates.     

Regioselectivity of the hydrolysis of 2-(1-alkoxyvinyl)-substituted imidazolidines, 1,3-thiazolidines,and 1,3-oxazolidines

2-(1-Alkoxyvinyl)-1,3-thiazolidines reacted with H₂O or D₂O in the presence of 105 mol % of p-toluenesulfonic acid or trifluoroacetic acid (20°C, 1 h) to give 2-acetyl-1,3-thiazolidine in quantitative yield. 2-(1-Alkoxyvinyl)-3,5-diphenylimidazolidines underwent hydrolysis in the presence of 20 mol % of an acid (20°C, 24 h) at the vinyloxy group with high regioselectivity yielding 2-acetylimidazolidines. Hydrolysis of 2-(1-alkoxyvinyl)-3-phenyl-1,3-oxazolidines in the presence of 10 mol % of p-toluenesulfonic acid (20°C, 5 days) takes two pathways, one of which involves the endocyclic C-O bond with ring opening and the other involves the vinyloxy group to produce 2-acetyl-3-phenyl-1,3-oxazolidine. Unlike phenyl-substituted 1,3-thiazolidines and imidazolidines, hydrolysis of their 3-methyl- and 3,5-dimethyl-substituted analogs in acid medium occurs mainly via ring opening. The observed hydrolysis pathways were interpreted in terms of B3PW91/6-311G(d,p) quantum-chemical calculations.     

Perthio- and perseleno-1,3-butadienes, -but-1-ene-3-ynes,and -[3]-cumulenes: one-step syntheses from 1,4-dilithio-1,3-butadiyne

[reaction: see text] Treatment of 1,4-dilithio-1,3-butadiyne (1) with dichalcogenides RSSR or RSeSeR affords dithio- and diseleno-1,3-butadiynes (2, 3), perthio- and perseleno-[3]-cumulenes (4, 5), perthio- and perseleno-1,3-butadienes (6, 7), and/or perthio- and perseleno-but-1-ene-3-ynes (8, 9). The products can be controlled by stoichiometry and temperature, by the presence or absence of oxygen, and by choice of the "R" group. By X-ray crystallography, hexa(methylthio)-1,3-butadiene is highly twisted, with a torsion angle [Phi(CCCC)] of 84.7 degrees and an elongated C(2)-C(3) distance of 1.484(3) A.     

Synthesis, Structure and Norbornene Polymerization Catalyzed by Palladium Complex Bearing the 1,3-Diphenyl-2-((quinolin-8-ylamino)-methylene)-propane-1,3-dione Ligand

The title complex 1,3-diphenyl-2-((quinolin-8-ylamino)methylene)propane-1,3-dione-palladium was synthesized by the reaction of 1,3-diphenyl-2-((quinolin-8-ylamino)-methylene)propane-1,3-dione with PdCl2 , and characterized by IR spectrum and single-crystal X-ray diffraction analysis. The crystal belongs to the orthorhombic system, space group P21212 with a = 21.838(4), b = 8.3952(17), c = 11.497(2), V = 2107.9(7)3 , C25H17ClN2O2Pd, Mr = 519.26, Z = 4, Dc = 1.636 g/cm3 , μ = 1.032 mm-1 , F (000) = 1040, the final R = 0.0307 and wR = 0.0778. This compound was investigated for the catalytic behavior towards norbornene (NB) vinyl addition polymerization. And the complex exhibits excellent catalytic activities up to 2.18×108 g of PNB (mol of Pd)-1 h-1 with high monomer conversion using methylaluminoxane (MAO) as the cocatalyst.     

NMR-untersuchungen an einigen 1,3-diinen

¹³C, ²⁹Si and ¹¹⁹Sn NMR data (chemical shifts and coupling constants) are reported for 1,3-diynes RCCCCR′ (R = R′ = H, t-C₄H₉, Si(CH₃)₃, Sn(CH₃)₃; R = Si(CH₃)₃, R′ = Sn(CH₃)₃). The data are in agreement with an increased polarity of the SnC bond in the 1,3-diynes as compared with alkynylstannanes.     

Oligodentate P,N ligands: N,N,N',N'-tetrakis(diphenylphosphanyl)-1,3-diaminobenzene complexes of rhodium, nickel and palladium

The oligodentate P,N ligand N,N,N',N'-tetrakis(diphenylphosphanyl)-1,3-diaminobenzene reacts with two equivalents of [{Rh(mu-Cl)(COD)}(2)], [NiBr(2)(DME)] or [PdCl(2)(NCMe)(2)](COD = 1,5-cyclooctadiene, DME = dimethoxyethane) in dichloromethane to give the tetranuclear complex [1,3-{cis-Rh(COD)(mu-Cl)(2)Rh(PPh(2))(2)N}(2)C(6)H(4)](1) or the dinuclear complexes [1,3-{cis-NiBr(2)(PPh(2))(2)N}(2)C(6)H(4)](2) and [1,3-{cis-PdCl(2)(PPh(2))(2)N}(2)C(6)H(4)](3), respectively. Compounds 1-3 were characterised by NMR ((1)H, (13)C, (31)P) and IR spectroscopy. The molecular structure of 2 and 3 shows the formation of a bis-chelate complex with M-P-N-P four-membered rings (M = Pd, Ni). An N,N,N',N'-tetrakis(diphenylphosphanyl)-1,3-diaminobenzene/Pd(OAc)(2) mixture was used for the copolymerisation of carbon monoxide with ethene or ethylidenenorbornene. Compound 1 was employed as catalyst in the hydrogenation of styrene.     

Crystal Structure of 1-Phenyl-1,3-butandione Benzidine Diketoimine

1-Phenyl-1,3-butandione benzidine diketoimine 2a (C32H28N2O2,Mr=472.56) was synthesized in high yield by the reaction of 1-phenyl-1,3-butandione with benzidine in absolute ethanol,and determined by X-ray structure analysis. It crystallizes in the orthorhombic system,space group P21/c with a=7.9839(16),b=12.910(3),c=12.358(3),α=90.00,β=93.71(3),γ= 90.00°,V=1271.1(4)3,Z=2,Dc=1.235 g/cm3,μ=0.077 mm-1,F(000)=500,the final R= 0.0717 and wR=0.1187. It presents a linear centrosymmetric framework constituted by a linkage of benzidine as a bridge and two terminal 1-phenyl-1,3-butanedione moieties.     

Substituted 2-methylene-1,3-oxazolidines, -1,3-thiazolidines, -1,3-benzothiazines, -1,3-oxazines, and substituted imidazopyrimidinediones from Cl(CH2)nNCO and Cl(CH2)nNCS and active methylene compounds

The reaction of omega-chloroalkyl isocyanates Cl(CH2)nNCO (n = 2 (2), 3 (4)) and isothiocyanate Cl(CH2)2NCS (3) with active methylene compounds CH2YY' 1 in the presence of Et3N or Na give 2-YY'-methylene-1,3-oxazolidines, (E,Z)-1,3-thiazolidines, and 1,3-oxazines from 2, 3, and 4, respectively. 2-(Chloromethyl)phenyl isocyanate 8 gives with 1 the corresponding benzo-oxazines. Ethyl 2-isothiocyanatobenzoate 10 gives the corresponding benzothiazolinone, whereas the analogous isocyanate 12 gives noncyclic enols. Ethoxycarbonyl isothiocyanate 14 gives an open-chain thioenol or an enol-thioamide. The cyanoamides CH2(CN)CONHR, R = H, Me, CHPh2, give with Et3N and 2 the bicyclic imidazopyrimidinediones 16, derived from two molecules of 2, but with their preformed Na salt they give the 1,3-oxazolidines. Reaction of cyanoacetamide with 3 in the presence of Na gave a tricyclic triaza(thia)indacene, derived from two molecules of 3. A reaction mechanism involving an initial attack of the anion 1- on the N=C=X (X = O, S) moiety gives an anion 18, which cyclizes intramolecularly and after tautomerization gives the mono-ring heterocycle. With the cyanoamides, the N- site of the ambident ion 18 attacks another molecule of 2 giving the anion 20, which by intramolecular attack on the CN, followed by expulsion of the Cl- gives the bicyclic 16 after tautomerization.     

Parallel solid-phase synthesis and structural characterization of a library of highly substituted chiral 1,3-oxazolidines

The rapid parallel synthesis and characterization of diverse chirally defined 1,3-oxazolidines is reported. Three diversity elements were incorporated in a 6 x 4 x 4 block approach to generate a 96-member 1,3-oxazolidine library. The synthetic route involved initial attachment of six nonracemic phenylglycidols, (2S,3S)1A-C and (2R,3R)-2A-C, to 2% cross-linked polystyrene resin via a chlorodiethylsilane linker (PS-DES), followed by regio- and stereoselective oxirane ring opening with four primary amines (3a-d). The key condensation reaction between the resulting polymer-bound beta-amino alcohols and four aldehydes (4a-d) was found to occur optimally in warm benzene (60 degrees C) in the presence of anhydrous magnesium sulfate. Cleavage of the oxazolidines from the resin support was achieved with TBAF to give the individual members (2R,4R,5R)-5Aaa-Cdd and (2S,4S,5S)-6Aaa-Cdd in good to excellent yields (51-99%) based on mass recovery. Purities of all these crude products was generally >85% (as measured by LCMS). 1H, 13C NMR, and 1D difference nOe of the library members confirmed the structural and stereochemical integrity of the substituents around the 1,3-oxazolidine core. The asymmetric induction at C-2 (cis or trans to the C-4 substituent) ratio ranged from 4 to I to 49 to 1 across the library. This report highlights the versatility of the 1,3-oxazolidine heterocycle as a scaffold for concise parallel library construction and opens the way for high-throughput screening of such compounds in the biological sphere.     

Synthesis of the C2 Symmetric 1,3-Dicyclohexyl-1,3-Propanediol and Diamine Enantiomers

The parent C₂-symmetric (R,R)- and (S,S)-1,3-dicyclohexyl-1,3-propanediols and diamines are readily obtained from the corresponding diphenyldiol precursors.     

One-step synthesis of some polyfluoroalkylated 1,3-benzodioxoles, 4H-1,3-benzodioxins and dibenzo[d,f] [1,3]dioxepins

Several polyfluoroalkylated heterocyclic compounds containing methylenedioxy group such as 2-(F-alkyl) substituted 1,3-benzodioxole, piperonal, 4H-1,3-benzodioxin, 1,3-dioxolane and 6-(F-alkyl) substituted dibenzo[d, f][1,3]dioxepin have been prepared through double Michael-addition reactions of 2,2-dihydropolyfluoroalkanoates with the corresponding diphenols or diols in high yields.     

Cycloaddition reactions of allenylphosphonates and related allenes with dialkyl acetylenedicarboxylates, 1,3-diphenylisobenzofuran, and anthracene

Cycloaddition reactions of allenylphosphonates [(RO)(2)P(O)[(R(1))C═C═CR(2)(2)] with dialkyl acetylenedicarboxylates, 1,3-diphenylisobenzofuran, and anthracene have been investigated and compared with those of allenoates [(EtO(2)C)RC═C═CH(2)] and allenylphosphine oxides [Ph(2)P(O)(R(1))C═C═CR(2)(2)] in selected cases. Allenylphosphonates (RO)(2)P(O)(Ar)C═C═CH(2) with an α-aryl group preferentially undergo [4 + 2] cycloaddition with DMAD/DEAD under thermal activation, but in addition to the expected 1:1 (allene: DMAD) product, the reaction also leads to 1:2 as well as 2:1 products that were not reported before. When an extra vinyl group is present at the γ-carbon of allenylphosphonate [e.g., (OCH(2)CMe(2)CH(2)O)P(O)(Ph)C═C═CH(C═CHMe)], [4 + 2] cycloaddition takes place utilizing either the vinylic or the aryl end, but additionally a novel cyclization wherein complete opening of the [β,γ] carbon-carbon double bond of the allene is realized. In contrast to these, the reaction of allenylphosphonate (OCH(2)CMe(2)CH(2)O)P(O)(H)C═C═CMe(2) possessing a terminal ═CMe(2) group with DMAD occurs by both [2 + 2] cycloaddition and ene reaction. While the reaction of ═CH(2) terminal allenylphosphonates as well as allenylphosphine oxides with 1,3-diphenylisobenzofuran afforded preferentially endo-[4 + 2] cycloaddition products via [α,β] attack, the analogous allenoates [(EtO(2)C)RC═C═CH(2)] underwent exo-[4 + 2] cyclization. Under similar conditions, allenylphosphonates with a terminal ═CR(2) group gave only [β,γ]-cycloaddition products. An unusual ring-opening of a [4 + 2] cycloaddition product followed by ring-closing via [4 + 4] cycloaddition, as revealed by (31)P NMR spectroscopy, is reported. Anthracene reacted in a manner similar to 1,3-diphenylisobenzofuran, albeit with lower reactivity. Key products, including a set of exo- and endo- [4 + 2] cycloaddition products, have been characterized by single crystal X-ray crystallography.     

Synthese und Eigenschaften der 1,3-Benzazaphosphole

Synthesis and Properties of the 1,3-Benzazaphospholes 1H-1,3-Benzazaphospholes (R = H, CH₃, C₆H₅, N(CH₃)₂) are synthesized not only rom o-aminophenylphosphines and different cyclisation compounds such as R? C(OR)?NH · HCl, R? C(O)Cl, R? COOR′, R? C(OCH₃)₂NR′₂, or Cl₂C?N(CH₃)₂Cl but also from secondary o-aminophenylphosphines PRH? C₆H₄? NH₂ (R = C₆H₅, C₂H₅) and CH₃? C(OR)?NH · HCl under elimination of ether or from 1,3-benzazaphospholines after oxidation or thermal treatment. Whereas the 1,3-benzazaphospholes don't react with acetyl chloride or methyl iodide the N-acetyl- and P-methyl-1,3-benzazaphospholes are formed starting with the ambident anion. Further reactions of the 1,3-benzazaphospholes and the nmr data of the compounds prepared are discussed.      

Photochemical and discharge-driven pathways to aromatic products from 1,3-butadiene

A detailed study of the photochemical and discharge-driven pathways taken by gas-phase 1,3-butadiene has been carried out. Photolysis or discharge excitation was initiated inside a short reaction tube attached to the outlet of a pulsed valve. Bath gas temperatures near 100 K were achieved in the reaction tube by the constrained expansion of the gas mixture into the tube, simulating temperatures of relevance in Titan's atmosphere. Photolysis of 1,3-butadiene was initiated at 218 nm with a laser pulse that counter-propagated the reaction tube. Discharge excitation was carried out using discharge electrodes imbedded in the reaction tube walls, enabling the study of the photochemical and discharge products under similar conditions. Products were detected using either single-photon VUV photoionization (118 nm = 10.5 eV) or resonant two-photon ionization (R(2)PI) spectroscopy in a time-of-flight mass spectrometer. Emphasis was placed on characterization of the aromatic products formed, since these may be of particular relevance to Titan's atmosphere, where benzene has been positively identified and 1,3-butadiene is projected as the principle pathway to its formation. Consistent with previous studies of the photodissociation of 1,3-butadiene, C(3)H(3) + CH(3) is the dominant primary product formed. Under the temperature-pressure conditions present in the reaction tube (T approximately 75-100 K, P = 50 mbar), C(6)H(6) is the dominant secondary photochemical product formed. A 1:1 C(4)H(6):C(4)D(6) mixture was used to prove that the C(6)H(6) product was formed by recombination of two C(3)H(3) radicals; however, a careful search for benzene revealed none, indicating that less than 1% of the C(6)H(6) formed in the reaction tube is benzene. This is consistent with expectations for these temperatures and pressures based on previous modeling of propargyl recombination. Two aromatic products were observed from the photochemistry: ethylbenzene and 3-phenylpropyne. Plausible pathways leading to these products are proposed. In the discharge, C(3)H(3) + CH(3) are also identified as significant primary neutral products and C(6)H(6) as a dominant higher-mass product. In this case, the C(6)H(6) was identified as benzene via its R2PI spectrum, appearing with intensity about 10 times larger than any other aromatic formed in the discharge. R2PI spectra of a total of about 15 aromatic products were recorded from the 1,3-butadiene discharge, among them toluene; styrene; phenylacetylene; o-, m-, and p-xylene; ethylbenzene; indane; indene; beta-methylstyrene; and naphthalene. Previously unidentified spectra in the m/z 142 and 144 mass channels were positively identified as the 1,3- and 1,4-isomers of phenylcyclopentadiene and the analogous 1-phenylcyclopentene.     

1H-1,3-diazepines, 5H-1,3-diazepines, 1,3-diazepinones, and 2,4-diazabicyclo[3.2.0]heptenes

Tetrazolo[1,5-a]pyridines/2-azidopyridines 1 undergo photochemical nitrogen elimination and ring expansion to 1,3-diazacyclohepta-1,2,4,6-tetraenes 3, which react with alcohols to afford 2-alkoxy-1H-1,3-diazepines 4 (5), with secondary amines to 2-dialkylamino-5H-1,3-diazepines 16, sometimes via isolable 2-dialkylamino-1H-1,3-diazepines 15, and with water to 1,3-diazepin-2-ones 19. The latter are also obtained by elimination of isobutene or propene from 2-tert-butoxy- or 2-isopropoxy-1H-1,3-diazepines 4 or 5. 1,3-Diazepin-2-one 22B and 1,3-diazepin-4-one 24 were obtained from hydrolysis of the corresponding 4-chlorodiazepines. Diazepinones 19 undergo photochemical ring closure to diazabicycloheptenones 25 in high yields. The 2-alkoxy-1H-1,3-diazepines 4 and 5 interconvert by rapid proton exchange between positions N1 and N3. The free energies of activation for the proton exchange were measured by the Forsén-Hoffman method as DeltaG([double dagger])298= 16.2 +/- 0.6 kcal mol(-1) as an average for 4a-c in CD2Cl2, acetone-d6, and methanol-d4, and 14.1 +/- 0.6 kcal mol(-1) for in 4c acetone/D2O. The structures of 2-methoxy-5,6-bis(trifluoromethyl)-1H-1,3-diazepine 4k, 1,2-dihydro-4-diethylamino-5H-1,3-diazepin-2-one 22bB, and diazabicycloheptanone were 26 determined by X-ray crystallography. The former represents the first reported X-ray crystal structure of any monocyclic N-unsubstituted 1H-azepine.