- Toward a Scalable Synthesis and Process for EMA401, Part II: Development and Scale-Up of a Pyridine- A nd Piperidine-Free Knoevenagel-Doebner Condensation
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During route scouting for EMA401 (1), an angiotensin II type 2 antagonist, we identified the synthesis of key amino acid intermediate 2 via its cinnamic acid derivative 3 as a streamlined option. In general, cinnamic acids can be synthesized from the corresponding aldehydes by a Knoevenagel-Doebner condensation in pyridine with piperidine as an organocatalyst. We aimed to replace both of these reagents and found novel conditions involving toluene as the solvent and morpholine as the organocatalyst. Scale-up of the process allowed the production of 25 kg of cinnamic acid 3 that was of the quality required for process development of the subsequent phenylalanine ammonia lyase-catalyzed step. The modified conditions were found to be widely applicable to alternative aldehydes and thus are of relevance to practitioners of chemical scale-up.
- Hardegger, Leo A.,Humair, Roger,Sidler, Eric
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p. 1756 - 1762
(2020/10/26)
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- The Cooperative Effect of Both Molecular and Supramolecular Chirality on Cell Adhesion
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Although helical nanofibrous structures have great influence on cell adhesion, the role played by chiral molecules in these structures on cells behavior has usually been ignored. The chirality of helical nanofibers is inverted by the odd–even effect of methylene units from homochiral l-phenylalanine derivative during assembly. An increase in cell adhesion on left-handed nanofibers and weak influence of cell behaviors on right-handed nanofibers are observed, even though both were derived from l-phenylalanine derivatives. Weak and negative influences on cell behavior was also observed for left- and right-handed nanofibers derived from d-phenylalanine, respectively. The effect on cell adhesion of single chiral molecules and helical nanofibers may be mutually offset.
- Liu, Jinying,Yuan, Feng,Ma, Xiaoyu,Auphedeous, Dang-i Y.,Zhao, Changli,Liu, Chuntai,Shen, Changyu,Feng, Chuanliang
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supporting information
p. 6475 - 6479
(2018/05/08)
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- NOVEL MONOMERS FROM BIOMASS
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Compounds derived from biomass, e.g., cellulose and lignins, methods of forming such compounds and polymers and products formed using such compounds.
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-
Paragraph 0249-0251
(2017/09/02)
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- Synthesis and characterization of new aromatic Co-polyamides
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Six new aromatic Co-polyamides CoP1-CoP6 were prepared by direct Yamazaki's polycondensation reaction of various aliphatic and aromatic dicarboxylic acid (adipic acid, phthalic acid, terephthalic acid and 4-phenylenediacrylic acid) with new various types of aromatic diamine monomers: monomers containing flexible linkages (methylene group), Schiff-base diamine monomer and diamine monomer containing pyridine heterocyclic group and bearing bulky aromatic pendant groups in the 4-position of the pyridine ring, in the presence of LiCl in pyridine and triphenyl phosphite as condensing agents in N-methyl-2-pyrrolidinone as solvent. 4-Phenylenediacrylic acid (PPDAA) was prepared by the condensation reaction of terephthalaldehyde with malonic acid in the presence of pyridine. The monomers were characterized by FTIR and 1H NMR. The resulting polyamides were characterized by FTIR and 1H NMR and their physical properties including solubility, thermal stability and thermal behaviour were studied as well. All of these new polymers show good solubility in polar aprotic solvents and very good thermal stability.
- Mutar, Mohammed A.
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p. S45 - S52
(2016/10/19)
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- Fabrication of nanocrystals from diolefin derivatives and their solid-state photoreaction behavior
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Nanocrystals of seven p-phenylenediacrylates, i.e., dimethyl (la), didecyl (lb), diundecyl (1c), ditetradecyl (1d), dipentadecyl (1e), dioctadecyl (1f), and dicholesteroyl (1g) derivatives, and 2,5-distyrylpyrazine (2) were fabricated by the reprecipitation method and their photochemical reaction behaviors were investigated in comparison to those of bulk crystals. The bulk crystals of 1a- 1c and 2 were found to be photoreactive, whereas those of 1d-1g were less photoreactive. In contrast, all of the nanocrystals of 1a-1g and 2 showed high photoreactivity. Nanocrystals of la and 2 were demonstrated to have the same packing as the corresponding polymerizable bulk crystals, and they gave the corresponding polymers by photoirradiation. The polymer crystal structures in their nanocrystals were confirmed to be the same as those in bulk crystals by X-ray and electron diffraction analyses. Their single-crystal-to-single-crystal transformation was established by their nanocrystallization. On the other hand, other nanocrystals (1b-1g) were found to have different packings compared with the corresponding bulk crystals. After photoirradiation, their crystallinity was degraded to form amorphous products.
- Miura, Hirohiko,Takahashi, Shu,Kasai, Hitoshi,Okada, Shuji,Yase, Kiyoshi,Oikawa, Hidetoshi,Nakanishi, Hachiro
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experimental part
p. 510 - 517
(2011/10/09)
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- Reactivity of substituted and unsubstituted diphenylphosphonium diylides towards carbonic acids derivatives
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In order to further delimit the scope of application of diphenylphosphonium diylides, their reactivity towards carbonic acid derivatives was investigated. Non-stabilized diylides react with ethyl carbonate to give new monoylide intermediates which lead, by in situ Wittig reaction with carbonyl compounds, to the synthesis of α,β-unsaturated esters or acids the double bond being di- or trisubstituted. The reaction proceeds in mild conditions and with high E stereoselectivity. Stabilized diylides are inactive towards carbonates but semi-stabilized diylides react with ethyl carbonate leading to the synthesis of non-functionalized alkenes instead of the α,β-unsaturated esters or acids.
- Cristau,Taillefer
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p. 1507 - 1522
(2007/10/03)
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- Photoreactive copoly(amide-imide)s derived from 1,4-phenylenediacrylic acid and various bis(trimellitimide)s and diisocyanates
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Three bis(trimellitimide)s were prepared by condensation of the corresponding aromatic diamines with trimellitic anhydride.Two series of structurally new photoreactive copoly(amide-imide)s were synthesized by the direct polycondensation of these bis(trimellitimide)s and 1,4-phenylenediacrylic acid as comonomer with 4,4′-diphenylmethanediisocyanate (series 1) and 1,6-diisocyanatohexane (series 2), respectively. The polycondensation reaction was carried out in N-methyl-2-pyrrolidone in the presence of tripropylamine as catalyst. All of the copoly(amide-imide)s soluble in polar aprotic solvents afforded transparent, flexible and tough films. Upon irradiation in solution the p-phenylenediacryloyl unit undergoes trans-cis photoisomerization and (2 + 2)photocycloaddition. Polymers of series 1 (all fully aromatic amides) undergo also a photo-Fries rearrangement. On the contrary, the photo-Fries reaction is completely suppressed for polymers of series 2 (containing an aliphatic amide moiety).The same situation is observed in the case of polymer films. The wholly aromatic copoly(amide-imide)s show no discernible transition before decomposition, whereas the aliphatic-aromatic copoly(amide-imide)s show well-defined melting points (Tm) in the first DSC heating traces.
- Onciu, Marioara,Chiriac, Constantin I.,Vlad, Stelian,Stoica, Gheorghe,Grigoriu, George,Timpu, Daniel
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p. 641 - 648
(2007/10/03)
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- Synthesis and Properties of 4,4,9,9-Tetramethylparacyclophane-5,6,7,8-tetrone
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The synthesis of 4,4,9,9-tetramethylparacyclophane-5,6,7,8-tetrone (26) has been achieved in a multistep procedure.Compound 26 is the first cyclic tetraketone whose structure has been studied by X-ray analysis.The key intermediates were 4,4,9,9-tetramethylparacyclophane-6,7-dione (22), 6,7-bis-4,4,9,9-tetramethylparacyclophane-5,7-diene (24), and two epimeric 5,8-dihydroxy-4,4,9,9-tetramethylparacyclophane-6,7-diones 25a and 25b.X-ray analyses have been performed on 24, 25b and 26.That on 24 reveals a dihedral angle of 57 deg between the two silyenol ether groups.The product analyses and the configurations of 25a and 25b together with the isolation of the bis(epoxide) intermediate 28 allow conclusions to be drawn on the oxidation mechanism of 24 with m-CPBA (Rubottom reaction).The stability of 26 is ascribed to steric factors.
- Gleiter, Rolf,Kraemer, Rolf,Irngartinger, Hermann,Bissinger, Claus
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p. 252 - 258
(2007/10/02)
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- Synthesis and characterization of derivatized capped porhyrins
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The syntheses of porphyrins carrying either a fully hydrophobic cavity with a benzene moiety (32a,b) or a polar cavity with an amidobenzene (32c-d) are described.Terephthaldehyde (1) was converted to benzene-bisalkanoic acids (8, 10) and nitrobenzene-bisalkanoic acids (13 and 16) by using standard methods.The corresponding diacid chlorides 17a-d were used to acylate two equivalents of a β-unsubstituted pyrrole, and the ketonic groups were reduced by diborane.Following the transformation of the nitro function to the acetamide, appropriate modifications of the ethyl ester functions afforded the key bisformylpyrroles 25a-d.The cyanoacrylate-protected formyl pyrrole derivatives were monochlorinated at the α-methyl groups and condensed with two equivalents of an α-unsubstituted pyrrole to give the dipyrromethane dimers.Strong aqueous alkali caused saponification of the two ester groups and deprotection of the formyl functions to produce the dipyrromethane dimer 30, which, after thermal decarboxylation, was cyclized intramolecularly in acidic medium to give the porphyrins 32 (n = 4 or 5, X = H or NHCOCH3).
- Tang, Hang,Wijesekera, Tilak P.,Dolphin, David
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p. 1366 - 1374
(2007/10/02)
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- Aromatic Spiranes, XIV: Syntheses of 2,2'-Spirobi-(s-hydrindacene) and its precursors
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The title compound 35 was prepared by catalytic reduction of the diones 29a and 11a. 29a was synthesized by systematic anellation of fivemembered rings to the positions 5,6 and 5',6', resp., of 2,2'-spirobiindane.The preparation of 11a was achieved by Friedel-Crafts cyclisation of bis-(5-indanylmethyl)-malonic acid. s-Hydrindacene-1-one 5a was prepared as a precursor for the synthesis of 11a (see forthcoming publication) and its derivates as models for corresponding anellation and substitution reactions. - Keywords: s-Hydrindacene-1-one and derivates; Mono- and bisanellation; 2,2'-Spirobiindane; 1H-nmr spectra
- Neudeck, Horst K.
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p. 627 - 658
(2007/10/02)
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