- Kinetics and mechanism of the cleavage of phthalic anhydride in glacial acetic acid solvent containing aniline
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(Chemical Equation Presented) Apparent second-order rate constants (k napp) for the nucleophilic reaction of aniline (Ani) with phthalic anhydride (PAn) vary from 6.30 to 7.56 M-1 s-1 with the increase of temperature from 30 to 50°C in pure glacial acetic acid (AcOH). However, the values of pseudo-first-order rate constants (k s) for the acetolysis of PAn in pure AcOH increase from 16.5 × 10-4 to 10.7 × 10-3 s-1 with the increase of temperature from 30 to 50°C. The values of knapp and ks vary from 5.84 to 7.56 M-1 s-1 and from 35.1 × 10-4 to 12.4 × 10-4 s-1, respectively, with the increase of CH3CN content from 1% to 80% v/v in mixed AcOH solvents at 35°C. The plot of ks versus CH 3CN content shows a minimum (with 104 ks = 4.40 s-1) at 50% v/v CH3CN. Similarly, the variations of knapp and ks with the increasing content of tetrahydrofuran (THF) in mixed AcOH solvent reveal respective a maximum (with knapp = 17.5-15.6 M-1 s-1) at 40-60% v/v THF and a minimum (with ks = ～ 0-1.2 ～ 10-4 s-1) at 60-70% v/v THF. The respective values of ΔH* and Δ S * are 15.3 ± 1.2 kcal mol-1 and -20.1 ± 3.8 cal K-1 mo-1 for ks and 1.1 ± 0.5 kcal mol-1 and -51.2 ± 1.7 cal K-1 mol-1 for knapp, while the values of kn (= k napp/fb with fb representing the fraction of free aniline base) are almost independent of temperature within the range 30-50°C. A spectrophotometric approach has been described to determine fb in AcOH as well as mixed AcOH-CH3CN and AcOH-THF solvents. Thus, the observed data, obtained under different reaction conditions, have been explained quantitatively. An optimum reaction condition, within the domain of present reaction conditions, has been suggested for the maximum yield of the desired product, N-phenylphthalamic acid.
- Damit, Emmy Fadhiza,Ariffin, Azhar,Niyaz Khan
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Read Online
- Synthetic method of epinastine hydrochloride
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The invention relates to a synthesis method of epinastine hydrochloride. The method comprises the following steps: reacting phthalic anhydride with aniline to obtain a compound 1, reacting the compound 1 with polyphosphoric acid under certain conditions to perform cyclization to obtain a compound 2, reducing carbonyl of the compound 2 under certain conditions to obtain a compound 3, and carrying out chlorination reaction on the compound 3 to obtain a compound 4, carrying out cyano substitution reaction on the compound 4 to obtain a compound 5, reducing the compound 5 by using a carbon-nitrogenunsaturated bond to obtain a compound 6, reacting the compound 6 with cyanogen bromide, and forming hydrochloride by using hydrochloric acid to obtain a compound 7; according to the method, the epinastine hydrochloride is prepared from bulk chemical products, is extremely low in price and mild in reaction condition, avoids the use of azide compounds, and the method is suitable for large-scale industrial production. The prepared epinastine hydrochloride is high in purity and low in cost, and has higher market competitiveness.
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Paragraph 0031-0032
(2020/12/15)
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- Synthetic method of plant growth regulator
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The invention discloses a synthetic method of plant growth regulator, which includes steps of 1), mixing a compound shown in formula (I), a compound shown in formula (II) and first alkali catalyst; performing ammonolysis reaction to obtain a compound shown in formula (III); 2), mixing the compound shown in formula (III) and prepared in step 1) with water to obtain mixed solution; performing hydrolysis reaction and acidification to prepare a compound shown in (IV), namely, the plant growth regulator, wherein R1 and R2 are independently selected from hydrogen, alkyl group, alkyl, alkynyl or halogen atom; the synthetic method is simple in method, the reaction product is high in yield; the compound shown in formula (III) in the product has high content.
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Paragraph 0052; 0053; 0055; 0060; 0091-0094
(2017/11/18)
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- Water mediated, environmentally friendly, step-wise, tandem & one-pot syntheses of 2-(1H-benzo[d]imidazole-2-yl)-N-arylbenzamides
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Water mediated and environmentally friendly, step-wise, tandem & one-pot syntheses of 2-(1H-benzo[d]imidazole-2-yl)-N-arylbenzamide derivatives have been developed by simply combining phthalic anhydride, anilines and phenylenediammonium dihydrogenphosphate. This reaction has an easy workup, provides excellent yields, and uses water as the solvent which is considered to be relatively environmentally benign.
- Reddy, Yervala Dathu,Ramana Reddy, Chittireddy Venkata,Dubey, Pramod Kumar
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p. 2974 - 2979
(2014/01/06)
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- An expeditious synthesis of imides from phthalic, maleic and succinic anhydrides and chemoselective C=C reduction of maleic amide esters
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Phthalic, maleic and succinic anhydrides have been reacted with aromatic amines to obtain the corresponding monoacid monoamides. The latter have been each transformed into the corresponding cyclic imide derivatives by treating with SOCl2. Alternatively, anhydrides have been reacted with methanolic KOH to obtain monomethyl ester derivatives which on reaction with aromatic amines in the presence of EDC. HCl and HOBt give cyclic imide derivatives. Reaction of monoacid monoamides independently, with SOCl 2 at 0-5°C give the monoamide monoester derivatives. Treatment of monoamide monoester of malic anhydride with NaBH4 leads to the unusual reduction of C=C grouping as well as the carbonyl group of the ester group to from monoamide monoalcohol of succinic anhydride. Preparation of monoamide monoalcohol of succinic anhydride can also be achieved by chemoselective reduction of monoamide monoester of malic anhydride with Mg turnings yielding monoamide monoester of succinic anhydride followed by reduction of the latter with NaBH4.
- Kumar, Padam Praveen,Reddy, Y. Dathu,Kumari, Y. Bharathi,Devi, B. Rama,Dubey
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p. 392 - 398
(2014/05/06)
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- Aza-DielsAlder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome
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The synthesis of 5-substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)- ones via [4 + 2] imino-DielsAlder cyclization from N-aryl-3- hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3- hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl) vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed.
- Jha, Amitabh,Chou, Ting-Yi,ALJaroudi, Zainab,Ellis, Bobby D.,Cameron, T. Stanley
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supporting information
p. 848 - 857
(2014/05/06)
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- A facile and green synthesis of N-substituted imides
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Anhydrides 1, 6 and 10 have been reacted, independently, with aromatic primary amines 2 in solid phase by simple physical grinding of reactants with p-toluenesulphonicacid as a catalyst to yield corresponding open chain derivatives, monoacid monoamides3,7 and 11 respectively. The latter have each been transformed into the corresponding cyclic derivatives, i.e. imides 5, 9 and 13 respectively in solid phase by simple physical grinding of each with K 2CO3, alkylating agent and tetrabutylammoniumbromide as a catalyst with short reaction times. These cyclic imides can also be obtained by physical grinding of each of 3, 7 and 11 with dicyclohexylcarbodimide as a dehydrating agent in solid phase.
- Kumar, Padam Praveen,Rama Devi,Dubey
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p. 1166 - 1171
(2013/09/24)
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- Synthesis and in vitro evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitors
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The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have been described so far. Here, we describe the synthesis of N-substituted maleimides and their pharmacological evaluation on the recombinant human fatty acid amide hydrolase (FAAH) and on the purified human MGL. A few N-arylmaleimides were previously described (Saario, S. M.; Salo, O. M.; Nevalainen, T.; Poso, A.; Laitinen, J. T.; Jarvinen, T.; Niemi, R. Characterization of the Sulfhydryl-Sensitive Site in the Enzyme Responsible for Hydrolysis of 2-Arachidonoylglycerol in Rat Cerebellar Membranes. Chem. Biol. 2005, 12, 649-656) as MGL inhibitors, and along these lines, we present a new set of maleimide derivatives that showed low micromolar IC50 and high selectivity toward MGL vs FAAH. Then, structure-activity relationships have been investigated and, for instance, 1-biphenyl-4-ylmethylmaleimide inhibits MGL with an IC50 value of 790 nM. Furthermore, rapid dilution experiments reveal that these compounds act as irreversible inhibitors. In conclusion, N-substituted maleimides constitute a promising class of potent and selective MGL inhibitors.
- Matuszak, Nicolas,Muccioli, Giulio G.,Labar, Geoffray,Lambert, Didier M.
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experimental part
p. 7410 - 7420
(2010/04/30)
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- Chemoselective acylation of amines in aqueous media
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Amines are efficiently acylated by both cyclic and acyclic anhydrides by dissolving them in an aqueous medium with the help of a surfactant, sodium dodecyl sulfate (SDS). Cyclic and acyclic anhydrides react with equal ease with an amine, and amines with various stereo-electronic factors react at the same rates with an anhydride. Chemoselective acylation of amines in the presence of phenols and thiols and of thiols in the presence of phenols has been achieved. No acidic or basic reagents are used during the reaction. No Chromatographic separation is required for isolation of the acylated products. Reactions in a neutral aqueous medium, easy isolation of products, and innocuous by-products make the present method a green chemical process. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Naik, Sarala,Bhattacharjya, Gitalee,Talukdar, Bandana,Patel, Bhisma K.
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p. 1254 - 1260
(2007/10/03)
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- Rational Design of an Indolebutanoic Acid Derivative as a Novel Aldose Reductase Inhibitor Based on Docking and 3D QSAR Studies of Phenethylamine Derivatives
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A series of 45 phenethylamine derivatives were synthesized and evaluated for their inhibitory activity against pig kidney aldose reductase (ALR2, EC 1.1.1.21). Their IC50 values ranged from 400 μM to 24 μM. The binding modes of compounds at the active site of ALR2 were examined using flexible docking. The results indicated that phenethylamine derivatives nicely fit into the active pocket of ALR2 by forming various hydrogen bonding and hydrophobic interactions. 3D-QSAR analysis was also conducted using FlexX-docked alignment of the compounds. The best prediction was obtained by CoMSIA combined with hydrophobic and hydrogen bond donor/acceptor field (q 2 = 0.557, r2 = 0.934). A new derivative, 4-oxo-4-(4-hydroxyindole)butanoic acid, was designed, taking into account the CoMSIA field and the binding mode derived by FlexX docking. This rationally designed compound exhibits an ALR2 inhibition with an IC50 value of 7.4 μM, which compares favorably to that of a well-known ALR2 inhibitor, tolrestat (IC50 = 16 μM) and represents a potency approximately 240-fold higher than that of an original phenethylamine lead compound, YUA001.
- Sun, Won Suck,Park, Yoon Sun,Yoo, Jakyung,Park, Ki Duk,Kim, Sung Han,Kim, Jung-Han,Park, Hyun-Ju
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p. 5619 - 5627
(2007/10/03)
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- Studies in large ring compounds: Synthesis of some new morphanthrindines and diazocines
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A novel method for the synthesis of 2 or 3-substituted 5,6-dihydro-6,11-dioxo-morphanthridines (2) involving the cyclisation of anilinic acid (1) with PPA/AcOH has been developed. A new heterocyclic system, 2 or 3-Substituted 5,6,11,12-tetrahydrodibenzo[b, f] [1,4]diazocine-6,11-diones(4) has been synthesized with excellent yields.
- Pawar,Bhusare,Pawar,Bhawal
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p. 1929 - 1936
(2007/10/03)
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- Microwave assisted synthesis of N-Arylphthalamic acids with hyperlipidemic activity
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A series of substituted N-arylphthalamic acids 3a-i has been synthesized by the reaction of phthalic anhydride 1 and aryl- or heterocyclic amines 2a-i, in the absence of solvents, in a domestic microwave oven. The formation of nine N-arylphthalamic acids was accomplished in 1-3 min giving excellent yields for compounds 3a-g, but moderate yield of compounds 3h and 3i, respectively. Compounds 3h and 3i are new. Interestingly, N-arylphthalamic acids 3a-i induced hyperlipidemia in Swiss white mice and also increased animals' body weight.
- Sena, Vera L.M,Srivastava, Rajendra M,Oliveira, Shalom P,Lima, Vera L.M
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p. 2671 - 2674
(2007/10/03)
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- The cyclisation of substituted phthalanilic acids in acetic acid solution. A kinetic study of substituted N-phenylphthalimide formation
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One novel and ten known substituted 3′- and 4′-phthalanilic acids have been prepared. These have been cyclised to two novel and nine known substituted N-phenylphthalimides by heating with glacial acetic acid. Both phthalanilic acids and imides have been characterised in detail and spectroscopic data are given. The kinetics of cyclisation for phthalanilic acids has been examined in detail, and it has emerged that a complex mechanism is operating. This initially involves a reversible, solvent assisted intramolecular nucleophilic attack by amide nitrogen on the carboxylic acid carbonyl. Clear evidence is seen for a long-lived intermediate as a precursor to imide formation. The observed kinetics are rationalised using a model of rapid pre-equilibration, followed by the slow breakdown of the intermediate to imide. Observed rate constants for pre-equilibration show a well behaved, linear Hammett plot (ρ = -1.1), whereas those for formation of imide do not.
- Perry, Christopher J.,Parveen, Zahida
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p. 512 - 521
(2007/10/03)
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- Effect of cyclodextrin on the intramolecular catalysis of amide hydrolysis
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The hydrolysis reaction of phthalamic acids (HOOCArCONHR, R = p-NO2Ph 1a, Ph 1b, adamantyl 1c) and N-phenyl maleamic acid 2b was studied in the presence of hydroxypropyl-β-cyclodextrin (HPCD) in acid solution. The reactions of 1a and 1b were studied also in the presence of β-cyclodextrin (β-CD). All the compounds formed inclusion complexes with HPCD, and the association constant was determined from the change in absorption of the substrate when the host is added in the case of 1a (90 M-1) and 2b (49 M-1). For 1c (4 × 104 M-1) a competition method was used, and for 1b the association equilibrium constant was obtained from the kinetic data (37 M-1) because it is too reactive for the spectrophotometric method. Both cyclodextrins strongly inhibited the reactions, and analysis of the kinetic data for HPCD indicated that the reactions of complexed 1a, 1b, and 2b are at least 10-30 times slower than in the bulk solution whereas 1c reacts only 4.6 times slower when it is complexed. The inhibition is attributed to changes in the geometry of the substrate due to interaction of the carboxylic group and/or the amide with the OH at the rim of the cyclodextrin. The differences in the relative effect observed for 1c are attributed to the formation of a tighter complex with this substrate.
- Granados,De Rossi
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p. 1548 - 1552
(2007/10/03)
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- Cyclodextrin effect on intramolecular catalysis
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HPCD inhibits the hydrolysis reaction of monoamides and monoesters of phthalic and maleic acid at pH 2. The magnitude of inhibition depends on the leaving group. For some of the substrates, the reaction in the cavity is more than 100 times slower than that in solution.
- Granados,Andres,De Rossi, R. Hoyos
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p. 405 - 406
(2007/10/03)
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- N-CYANOIMIDES: REACTIVITY WITH AMINE NUCLEOPHILES
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N-Cyanoimides are useful precursors to N-alkyl or N-aryl imides.Treatment of aromatic N-cyanoimides such as N-cyanophthalimide (1) with primary amines provides N-substituted imides directly, while aliphatic N-cyanoimides afford diamide intermediates which can be converted to N-substituted imides upon heating.
- Stephens, Randall W.,Domeier, Linda A.,Todd, Michael G.,Nelson, Veronica A.
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p. 733 - 736
(2007/10/02)
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- Morphanthridines: Part II - Syntheses of 5,6-Dihydro-6,11-dioxomorphanthridine, 1 (or 2)-Substituted 6,11-Dioxo-5,6-dihydromorphanthridines and 7H-12,13-Dihydro-7,12-dioxobenzonaphthazepine
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A novel method for the synthesis of substituted 5,6-dihydro-6,11-dioxomorphanthridines (IV) involving the cyclization of anilic acids (III) with PPA has been developed.A new heterocyclic system, 7H-12,13-dihydro-7,12-dioxobenzonaphthazepine (VII), has also been synthesized.
- Sinha, Ashok Kumar,Nizamuddin, S.
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- Triazine--antidote compositions and methods of use for cotton
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Herbicidal compositions comprising an active herbicidal compound of the triazine class selected from the group consisting of 2-chloro-4-ethylamino-6-isopropylamino-s-triazine and 2-(4-chloro-6-ethylamino-s-triazin-2-yl-amino)-2-methylpropionitrile, and antidote therefor, and methods of use; the antidote compound corresponds to N-phenylphthalamic acids having the formula STR1 in which R is tetrahydromonophthaloyl, halomonophthaloyl in which halo is chlorine or bromine from 1 to 4, inclusive, or monophthaloyl; R' is hydrogen or fluorine.
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