Ethynyl Derivatives Research Articles

Neutral and ionic aluminum, gallium, and indium compounds carrying two or three terminal ethynyl groups.

The syntheses of the ionic compounds [Li(+).2 dioxane (2,6-iPr(2)C(6)H(3)N(SiMe(3))Al(C triplebond CSiMe(3))(3))(-)].0.75 dioxane (1), [(Li(+))(2).(dioxane)(7)](0.5) [2,6-iPr(2)C(6)H(3)N(SiMe(3))Ga(C triplebond CSiMe(3))(3)(-)].1.5 dioxane (2), and [(Li(+))(2).(dioxane)(7)](0.5) [2,6-iPr(2)C(6)H(3)N(SiMe(3))In(C triplebond CSiMe(3))(3)(-)].1.5 dioxane (3) by the reaction of the corresponding organo metal chloride with LiC triplebond CSiMe(3) are reported. The neutral ethynyl compounds Br-Al(C triplebond CtBu)(2).2 THF (4), Cl-Ga(C triplebond CtBu)(2).THF (5), Cl-In(C triplebond CtBu)(2).2 THF (6), Al(C triplebond CtBu)(3).C[N(Me)CMe](2) (7), Ga(C triplebond CtBu)(3).dioxane (8), and In(C triplebond CtBu)(3).NEt(3) (9) have been obtained in good yields from the reaction of AlBr(3), GaCl(3), and InCl(3) with LiC triplebond CtBu in the presence of a Lewis base. Compound 7 is the first heterocyclic carbene substituted ethynyl derivative. Aluminum and gallium compounds with three terminal ethynyl groups Al(C triplebond CPh)(3).NMe(3) (10) and Ga(C triplebond CPh)(3).NMe(3) (11) have been prepared by the reaction of AlH(3).NMe(3) or GaH(3).NMe(3) with three equivalents of phenylethyne. All the above-mentioned compounds have been structurally studied. In compound 1 the lithium ion is coordinated to the three terminal ethynyl groups, whereas in compounds 2 and 3 the lithium is coordinated to the solvent (dioxane). Compound 8 crystallizes as a coordination polymer with dioxane molecules bridging the individual gallium units.

Palladium-Catalyzed Coupling Reactions of Paramagnetic Vinyl Halides

Suzuki. Heck and Sonogishira coupling reactions of paramagnetic vinyl bromides 1-6 gave monofunctional (7a,b), homobifunctional (8a,b, 24), and heterobifunctional pyrroline nitroxide; (9-19, 31) under mild conditions in aone-step reaction. From these compounds thiol-specific spin labels 26 and 28 and pyrroline nitroxide annulated heterocycles 30 and 32 were synthesized. The ethynyl derivative of pyrroline nitroxide 33 also can be used as an acetylene reactant in Larock indole synthesis to give the paramagnetic indole derivative 36.

Synthesis of controlled π-extended conjugate nanostructures of 1,1′-ferrocene

Synthesis of the ( E, E)-1,1′-ferrocene nanostructures having controlled π-extended conjugation was satisfactory carried out starting of 1′-[2-(1,3-dioxolan)]-1-formylferrocene ( 1). The molecular unit ( E)-1′-[2-(1,3-dioxolan)]-1-[β-( p-iodophenyl)ethenyl]ferrocene ( 2), was obtained in excellent yield by treatment of 1 with p-iodobenzyl triphenylphosphonium ylid followed by Z→ E isomerization, catalyzed by iodine, in quantitative yield. Compound ( E)- 2 was transformed in ( E)-1′-{2-(1,3-dioxolan)-1-[β-[4-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl]-ethenyl}ferrocene, ( E)- 4, by palladium catalyzed cross-coupling with 2-methyl-but-3-yn-2-ol. ( E)- 4 gives ( E)-1-[β-(4-ethynylphenyl)-ethenyl]-1′-[2-(1,3-dioxolan)]ferrocene ( E)- 5 by powder sodium hydroxide treatment. The molecular unit ( E, E)-1-{β-[4-(β-(1′-formylferrocenyl)-ethenyl)-phenylethynyl]-phenyl]-ethenyl}-1′-formylferrocene, ( E, E)- 6, was synthesized by palladium catalyzed cross-coupling between the p-iodophenyl derivative ( E)- 2 and their ethynyl derivative ( E)- 5, in good yield. The ( E, E)-1,1′-( p-iodophenyl)ethenyl ferrocene, ( E, E)- 7, was synthesized by reaction between 1,1′-diformylferrocene and the p-iodobenzyltriphenylphosphonium ylid, as a mixture of isomers which were purely isolated. Moreover, isomerization of the Z, Z and E, Z mixture to the E, E isomer, was induced by sunlight exposure, catalyzed by iodine, in quantitative yield. The ( E, E)-1,1′-[β-(4-ethynylphenyl)-ethenyl]ferrocene, ( E, E)- 10, was synthesized in good yield, by palladium catalyzed cross-coupling of compound ( E, E)- 7 with 2-methyl-but-3-yn-2-ol, followed by powder sodium hydroxide treatment.

Asymmetric Pauson-Khand reactions using camphor-derived chelating thiols as chiral controllers.

A convenient procedure for the preparation of enantiopure 10-(R-thio)-2-exo-bornanethiols from (1S)-camphor-10-thiol has been developed. The ethynyl derivatives of these thiols gave excellent diastereoselectivities (up to 98:2) in Pauson-Khand reactions with norbornene and norbornadiene through the intermediacy of a chelated dicobalt pentacarbonyl complex. Thermal reaction conditions starting from the preformed chelated complex gave better results than N-oxide-promoted runs with in situ generation of the chelated intermediate. The corresponding adducts have been elaborated through a protocol consisting of conjugate addition, samarium iodide-promoted cleavage of the chiral auxiliary, and retro-Diels-Alder reaction to afford 4-substituted 2-cyclopentenones in high enantiomeric purity.

Acidity trends in alpha,beta-unsaturated alkanes, silanes, germanes, and stannanes.

The gas-phase acidity of ethyl-, vinyl-, ethynyl-, and phenyl-substituted silanes, germanes, and stannanes has been measured by means of FT-ICR techniques. The effect of unsaturation on the intrinsic acidity of these compounds and the corresponding hydrocarbons was analyzed through the use of G2 ab initio and DFT calculations. In this way, it was possible to get a general picture of the acidity trends within group 14. As expected, the acid strength increases down the group, although the acidity differences between germanium and tin derivatives are already rather small. As has been found before for amines, phosphines, and arsines, the carbon, silicon, germanium, and tin alpha,beta-unsaturated compounds are stronger acids( )than their saturated analogues. The acidifying effect of unsaturation is much larger for carbon than for Si-, Ge-, and Sn-containing compounds. The allyl anion is better stabilized by resonance than its Si, Ge, and Sn analogues, [CH(2)(-)(delta)--CH(+)(delta)(') --CH(2)(-)(delta)](-) vs [CH(2)(-)(delta)()II = CH(-)(delta)()III - XH(2)(-)(delta)()IV](-) (X = Si, Ge, Sn). The enhanced acid strength of unsaturated compounds is essentially due to a greater stabilization of the anion with respect to the neutral, because the electronegativity of the alpha,beta-unsaturated carbon group increases with its degree of unsaturation. The phenyl derivatives are systematically weaker acids than the corresponding ethynyl derivatives by 15-20 kJ mol(-)(1). Experimentally, toluene acidity is very close to that of propyne, because the deprotonation of propyne takes place preferentially at the =CH group rather than at the -CH(3) group.

Magnetic properties after irradiation of poly( m-phenyleneethynylene) having diazo and nitronylnitroxide groups and its model compounds

In order to achieve a pure organic high-spin molecule, poly( m-phenyleneethynylene) derivative 1 having diazo groups and nitronyl nitroxide moieties alternately were designed. Its three model compounds, diphenylacetylene derivative 2, bis(phenylethynyl)benzene derivative 3, and oligomeric compound 4 having partial structure of 1 have been prepared by the coupling reaction of ethynyl derivatives of phenylnitronylnitroxide and iodo derivatives of diphenyldiazomethane. Field dependence of magnetization after irradiation of 2 and 3 in frozen solutions suggested that the photo-generated species have quartet and quintet ground states with J/ k B values of +1.75 and +1.09 K, respectively. However, spin interaction between carbene and nitronylnitroxide through 3,3′-diphenylacetylene moiety is not strong enough to form high-spin chain having long correlation length for 4.

Synthesis and Properties of Planar-Chiral (η6-Benzene)(η5-cyclopentadienyl)ruthenium(II) Complexes in an Optically Pure Form

Abstract Planar-chiral cyclopentadienylruthenium complexes [Ru(η5-1-CO2R*-2-Me-4-R1C5H2)(η6-C6H6)][X] (4 and 8) (R* = (l)- or (d)-menthyl; R1 = Me, Ph, t-Bu, 2-Naphthyl, or 4-BrC6H4; X = PF6 or BPh4) were synthesized in a diastereomerically pure form. The absolute configuration of 8b and 4c (R1 = Ph, t-Bu) were determined by an X-ray crystallographic analysis and those of the others were assigned on the basis of their optical properties including their CD spectra. Enantiopure complexes (SC1)-[Ru(η5-1-CONHBut-2-Me-4-R1C5H2)(η6-C6H6)][PF6] 9 and -[Ru(η5-1-CONHBut-2-Me-4-R1C5H2)(η6-C6H6)] [BPh4] 10, and (RC1)-9 and -10 were prepared from direct hydrolysis of diastereomeric complexes, followed by the reaction of amines. Replacement reactions of the bromo group in 9e (R1 = 4-BrC6H4) gave alkyl, phenyl, and ethynyl derivatives. Complexes [Ru(η5-1-CO2Et-2-Me-4-R1C5H2)(η6-C6H6)][PF6] 6 were also transformed to planar-chiral [Ru(η5-1-CO2Et-2-Me-4-R1C5H2)(CH3CN)3][X], which underwent ligand exchange reactions to afford carbonyl, phosphine, and π-arene complexes.

Synthesis and Reactions of Ethynyl Derivatives of Adamantanone, Verbanone, and Verbenone

Lithium acetylide was reacted with adamantanone, verbanone, and verbenone to obtain their hydroxyethynyl derivatives whose reaction with aqueous ammonia solution of silver nitrate gave the corresponding polycycloaliphatic silver acetylides. The latter react with iodine, yielding hydroxyethynyl iodides. Acetates of the adamantane-containing ethynyl alcohols were prepared.

Thermally Curing Aryl−Ethynyl End-Capped Imide Oligomers: Study of New Aromatic End Caps

Two new aryl−ethynyl end-cap model compounds, N-phenyl-4-(1-naphthylethynyl)phthalimide (1) and N-phenyl-4-(2-naphthylethynyl)phthalimide (3), were synthesized and characterized. The single-crystal molecular structure of 1 reveals an alternating “head to tail” packing mode whereas the “heads and tails” of 2 are aligned and not alternating. The thermal cure kinetics of 1 and 3 were analyzed using NMR and FT-IR spectroscopy, respectively, and compared to N-phenyl-4-phenylethynylphthalimide (2). In both cases the naphthyl−ethynyl model compounds reacted faster than the phenyl−ethynyl derivative. The end-capped imide oligomers analogues of 1 and 2, NETI-5 and PETI-5, respectively, were synthesized and their thermal cure kinetics were analyzed by DSC. The thermal cure kinetics of 1 and 2 best fit a first-order rate law. Compound 1 cures at faster rates than 2, although the calculated Ea values of 1 and 2 are statistically indistinguishable. The thermal cure kinetics of 2 and 3 also fit a first-order rate law a...

A novel way of preparing meso-substituted ethynylporphyrins and their derivatives by using 1,2,3-thiadiazole as a protecting group

Meso-(1,2,3-thiadiazol-4-yl) porphyrins are smoothly transformed to the corresponding ethynyl derivatives using potassium tert-butoxide as base. Some metal-catalyzed coupling reactions of these acetylenes are described.

Nucleosides and nucleotides. 175. Structural requirements of the sugar moiety for the antitumor activities of new nucleoside antimetabolites, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine and -uracil1.

We previously designed 1-(3-C-ethynyl-beta-d-ribo-pentofuranosyl)uracil (EUrd) and its cytosine congener (ECyd) as potential multifunctional antitumor nucleoside antimetabolites. They showed potent and broad-spectrum antitumor activity against various human and mouse tumor cells in vitro and in vivo. To clarify the structure-activity relationship of the sugar moiety, various 3'-C-carbon-substituted analogues, such as 1-propynyl, 1-butynyl, ethenyl, ethyl, and cyclopropyl derivatives, of ECyd and EUrd were synthesized. We also prepared 3'-deoxy analogues and 3'-homologues of ECyd and EUrd with different configurations to determine the role of the 3'-hydroxyl group and the length between the 3'-carbon atom and the ethynyl group and a 2'-ethynyl derivative of ECyd to determine the spatial requirements of the ethynyl group. The in vitro tumor cell growth inhibitory activities of these nucleosides against mouse leukemic L1210 and human KB cells showed that ECyd and EUrd were the most potent inhibitors in the series, with IC50 values of 0.016 and 0.13 microM for L1210 cells and 0.028 and 0.029 microM for KB cells, respectively. Only 3'-C-1-propynyl and -ethenyl derivatives of ECyd showed greatly reduced cytotoxicity. We found that the cytotoxic activity of these nucleosides predominantly depended on their first phosphorylation by uridine/cytidine kinase.

Synthesis and reactions of ethynylbenzocrown ethers

The interaction of 4’-iodobenzo-15-crown-5 and -18-crown-6 ethers with 2-methyl-3-butyn-2-ol and trimethylsilylacetylene followed by treatment of the reaction products with alkali yields ethynylbenzocrown ethers; chemical transformations such as cross- and homo-coupling and Cadiot–Chodkiewicz and Mannich reaction of the ethynyl derivatives have been carried out.

ChemInform Abstract: Nucleosides and Nucleotides. Part 154. New Neplanocin Analogues. Part 8. Synthesis and Biological Activity of 6′‐C‐Ethyl, ‐Ethenyl, and ‐ Ethynyl Derivatives of Neplanocin A.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The synthesis of chiral ferrocene ligands and their metal complexes

Starting from the well known N,N-dimethylaminoethylferrocene ( 1) {or N,N-dimethyl(1-ferrocenylethyl)amine}, further substitution of the cyclopentadienyl ring in an adjacent position enables formation of -iodo ( 2), -trimethylsilylethynyl ( 3) and -ethynyl ( 4) derivatives in good yields. From 4, fac-[manganese 1,2-bis(diphenylphosphinomethane)(tricarbonyl)acetylide] ( 5), trans-[rutheniumdi(1,2-bis(diphenylphosphinomethane))chloro-acetylide] ( 6) and trans-[osmiumdi(1,2-bis(diphenylphosphinomethane))chloro-acetylide] ( 7) have been synthesised and characterised. Electrochemical experiments in solution indicate that there is a decrease in polarisation and a decrease in the degree of metal-to-metal interaction in the chiral ferrocenyl metal-acetylides as opposed to the non-chiral analogues. Second harmonic generation (Kurtz powder) measurements are reported on the chiral metal complexes, but unfortunately negligible second-order non-linear activity was observed.

New neplanocin analogues. VIII. Synthesis and biological activity of 6'-C-ethyl, -ethenyl, and -ethynyl derivatives of neplanocin A.

This report describes the synthesis and antiviral effects of (6'R)-6'-C-ethynyl, -ethenyl, and -ethyl derivatives of neplanocin A (7a, 8a, and 9a, respectively) and the corresponding 6'S-diastereomers (7b, 8b, and 9b, respectively), as examples of 6'-C-substituted analogues of neplanocin A. Grignard reaction of the 6'-formyl derivative 4, which was readily prepared from neplanocin A, with ethynylmagnesium bromide gave a diastereomeric mixture of the corresponding 1,2-addition products 5a and 5b. After removal of the protecting groups, (6'R)- and (6'S)-6'-C-ethynylneplanocin A's (7a, 7b) were separated. The corresponding ethenyl derivatives 8a and 8b and ethyl derivatives 9a and 9b were prepared by catalytic hydrogenation of 7a and 7b, respectively. As compared to neplanocin A, the new neplanocin A derivatives were much weaker inhibitors of S-adenosyl-L-homocysteine hydrolase, the R-diastereomers being more inhibitory than the S-diastereomers. The decreasing order of activity was 7a > 8a > 7b > 9a > 8b > 9b. The cytotoxicity (for CEM cells) followed exactly the same order. Of these compounds, (6'R)-6'-C-ethynylneplanocin A (7a, RENPA) showed an antiviral activity spectrum that was comparable to, and an antiviral specificity that was higher than, that of neplanocin A. RENPA was particularly active against those viruses (i.e. vaccinia virus, vesicular stomatitis virus) that are known to be highly sensitive to AdoHcy hydrolase inhibitors.

Novel vinylation of a mercury(II) centre in [S2WS2HgCl2]2–by acetone: synthesis and structure of [PPh4]2[S2WS2Hg(CHCH2)2]·0.5Me2CO and its topochemical conversion into [PPh4]2[S2WS2Hg(CCH)2]·0.5MeCHO

Reaction of [PPh4]2[S2WS2HgCl2] with acetone affords a yellow vinyl complex [PPh4]2[S2WS2Hg(CHCH2)2]·0.5Me2CO which on standing in a desiccator for 3–4 months transforms to a black ethynyl derivative [PPh4]2[S2WS2Hg(CHCH)2]·0.5MeCHO.

2-Aralkynyl and 2-heteroalkynyl derivatives of adenosine-5'-N-ethyluronamide as selective A2a adenosine receptor agonists.

A series of new 2-aralkynyl and 2-heteroaralkynyl derivatives of NECA were synthesized and studied in binding and functional assays to assess their potency for the A2a compared to A1 adenosine receptors. Compounds bearing an aromatic or heteroaromatic ring, conjugated to the triple bond, showed generally weaker activity at the A2a receptor and lower selectivity (A2a vs A1) than the alkylakynyl derivatives previously reported. However, the (4-formylphenyl)-ethynyl derivative 17 showed affinity in the low nanomolar range and high selectivity (about 160-fold) for the A2a receptor. The presence of heteroatoms improved vasorelaxant activity, the 2-thiazolylethynyl derivative 30 being the most potent in the series. Introduction of methylene groups between the triple bond and the phenyl ring favored the A2a binding affinity, and the 5-phenyl-1-pentynyl derivative 24 was found to be highly potent and selective (about 180-fold) at A2a receptors. With regard to antiplatelet activity, the presence of aromatic or heteroaromatic rings decreased potency in comparison with that of NECA and of N-ethyl-1'-deoxy-1'-(6-amino-2-hexynyl-9H-purin-9-yl)-beta-D-ribofura nuronamide (HENECA). Introduction of a methylene group was effective in increasing antiaggregatory potency only when this group is linked to a heteroatom (31-35). From these data and those previously reported, the structure-activity relationships derived for the 2-alkynyl-substituted ribose uronamides would indicate that potentiation of A2a receptor affinity could be obtained by aromatic rings not conjugated with the triple bond or by heteroaromatic groups. As for A2a receptors on platelets, the presence of aromatic rings, either conjugated or unconjugated to the triple bond, is detrimental for the antiaggregatory activity. However, the introduction of polar groups alpha to the triple bond strongly increases the potency when steric hindrance is avoided. Some of the compounds included in this series retain interesting vasodilating properties and merit further investigation for their potential in the treatment of cardiovascular disorders.

ChemInform Abstract: Substituent Effects. Part 5. Vinyl and Ethynyl Derivatives. An Examination of the Interaction of Amino and Hydroxy Groups with C‐C Double and Triple Bonds

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Palladium(0)-Catalyzed Coupling Reactions of 2-Alkoxy-1-ethynylcyclopropanes with Aryl and Ethenyl Halides: Preparation of Cyclopropyl Substituted Ethynylarenes, Eneynes and Enediynes

2-Alkoxy-1-ethynylcyclopropanes 1-R 1 , readily available in diastereo- and enantiopure form, 2.3 undergo facile palladium-catalyzed cross- coupling reactions with various mono- and oligohaloarenes 2(a-c)-X, 4, 6, 9, 12, haloalkenes 14a-d and (E/Z)-1,2-diholoethenes [(E/Z)-18-X]. The trans- and trans/cis-(2-alkoxycyclopropyl)-ethynyl derivatives 3(a- c)-R 1 , 5, 7, 10, 13, 15a-d and (E)-19(22) were exclusively obtained in good to excellent yields. The coupling reaction thus opens the first direct access to configurotionally uniform (2-alkoxycyclopropyl)ethynyl substituted arenes, and 2-alkoxycyclopropyl substituted eneynes and enediynes. Catalytic hydrogenation of ethynylarenes 3(a-c)-R 1 , 10, and 13 smoothly afforded the corresponding (E/Z)-[(2-alkoxycyclopropyl)- ethenyl]arenes 24(a-c)-R 1 , 25 and 26, which are not directly accessi- ble by palladium(0)-catalyzed coupling reactions of (E)-2-alkoxy-1-ethe- nylcyclopropanes with haloarenes

Substituent effects. 5. Vinyl and ethynyl derivatives. An examination of the interaction of amino and hydroxy groups with carbon-carbon double and triple bonds

The effect of substituents on the energies of vinyl derivatives was examined with the use of group separation reactions with ethane to give propene and a substituted methane. The energy changes for these reactions were much smaller than those found for a corresponding set of acetyl derivatives. The bond dissociation energies (BDEs) for the vinyl derivatives were found to be linearly related to those of the related methyl derivatives with a slope close to unity. The average difference between BDEs in the two series was 12.1±1.5 kcal/mol, with the larger values found in the vinyl series. This is in accord with the difference in hybridization between vinyl and methyl. The results for the vinyl series stand in marked contrast to the acetyl series previously studied