cas 52250-50-7, 1-Phenyl-3,4-dihydroisoquinoline

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Parham et al.
p. 1606
(1978)
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Enhancement of the carbamate activation rate enabled syntheses of tetracyclic benzolactams: 8-oxoberbines and their 5- And 7-membered C-ring homologues
A route to the direct amidation of aromatic-ring-tetheredN-carbamoyl tetrahydroisoquinoline substrates was developed. This route enabled general access to 8-oxoberberines and their 5- and 7- membered C-ring homologues. It overcomes the undesired tandem side-reactions that result in the destruction of the isoquinoline backbone, which inevitably occurred under our previously reported superacidic carbamate activation method.
Kurouchi, Hiroaki
p. 653 - 658
(2021/02/06)

Tf2O/TTBP (2,4,6-Tri-tert-butylpyrimidine): An Alternative Amide Activation System for the Direct Transformations of Both Tertiary and Secondary Amides
Ten types of Tf2O/TTBP-mediated amide transformation reactions were investigated. The results showed that compared with pyridine derivatives 2,6-di-tert-butyl-4-methylpyridine (DTBMP) and 2-fluoropyridine (2-F-Pyr.), TTBP can serve as an alternative amide activation system for the direct transformation of both secondary and tertiary amides. For most surveyed examples, higher or comparable yields were generally obtained. In addition, Tf2O/TTBP combination was used to promote the condensation reactions of 2-(tert-butyldimethylsilyloxy)furan (TBSOF) with both tertiary and secondary amides, the one-pot reductive Bischler-Napieralski-type reaction of tertiary lactams, and Movassaghi and Hill's modern version of the Bischler-Napieralski reaction. The value of the Tf2O/TTBP-based methodology was further demonstrated by the concise and high-yielding syntheses of several natural products.
He, Qian,Ye, Jian-Liang,Xu, Fang-Fang,Geng, Hui,Chen, Ting-Ting,Chen, Hang,Huang, Pei-Qiang
(2021/09/28)

Enantioselective Allylation of Cyclic and In Situ Formed N-Unsubstituted Imines with Tetraol-Protected Allylboronates
Tetraol-protected α-chiral allylboronates are utilized in diastereo- and enantioselective transformations of cyclic imines (up to 98 %, d.r. 97 : 3, e.r. 99 : 1). An application to in situ formed N-unsubstituted imines gives in a consecutive one-pot sequence selective access to all four stereoisomers of the homoallylamine within minutes (up to 88 %, d.r. 81 : 19, e.r. 99 : 1). These results underline the usability, tuneability and stability of tetraol-based allylboronates.
Ullrich, Patrick,Schlamkow, Max A.,Choi, Ching-Yi,Kerkenpa?, Hannah,Hen?en, Birgit,Pietruszka, J?rg
supporting information
p. 6254 - 6257
(2021/11/03)

Diprotonative stabilization of ring-opened carbocationic intermediates: conversion of tetrahydroisoquinoline to triarylmethanes
Superacid-promoted conversion of tetrahydroisoquinolines to triarylmethanes via tandem reactions of C-N bond scission, Friedel-Crafts alkylation, C-O bond scission, and electrophilic aromatic amidation was developed. Dication formation was important for stabilizing the ring-opened carbocationic intermediate, which is a new role for diprotonation in reaction mechanisms. This journal is
Kurouchi, Hiroaki
p. 8313 - 8316
(2020/08/17)

Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity
The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with high enantioselectivity; therefore, this approach solves a long-standing challenge for imine ATH.
Barrios-Rivera, Jonathan,Xu, Yingjian,Wills, Martin
p. 6283 - 6287
(2020/09/02)

Superhydrophobic nickel/carbon core-shell nanocomposites for the hydrogen transfer reactions of nitrobenzene and N-heterocycles
In this work, catalytic hydrogen transfer as an effective, green, convenient and economical strategy is for the first time used to synthesize anilines and N-heterocyclic aromatic compounds from nitrobenzene and N-heterocycles in one step. Nevertheless, how to effectively reduce the possible effects of water on the catalyst by removal of the by-product water, and to further introduce water as the solvent based on green chemistry are still challenges. Since the structures and properties of carbon nanocomposites are easily modified by controllable construction, a one step pyrolysis process is used for controllable construction of micro/nano hierarchical carbon nanocomposites with core-shell structures and magnetic separation performance. Using various characterization methods and model reactions the relationship between the structure of Ni?NCFs (nickel-nitrogen-doped carbon frameworks) and catalytic performance was investigated, and the results show that there is a positive correlation between the catalytic performance and hydrophobicity of catalysts. Besides, the possible catalytically active sites, which are formed by the interaction of pyridinic N and graphitic N in the structure of nitrogen-doped graphene with the surfaces of Ni nanoparticles, should be pivotal to achieving the relatively high catalytic performance of materials. Due to its unique structure, the obtained Ni?NCF-700 catalyst with superhydrophobicity shows extraordinary performances toward the hydrogen transfer reaction of nitrobenzene and N-heterocycles in the aqueous state; meanwhile, it was also found that Ni?NCF-700 still retained its excellent catalytic activity and structural integrity after three cycles. Compared with traditional catalytic systems, our catalytic systems offer a highly effective, green and economical alternative for nitrobenzene and N-heterocycle transformation, and may open up a new avenue for simple construction of structure and activity defined carbon nanocomposite heterogeneous catalysts with superhydrophobicity.
Duan, Zhiying,Liu, Fangfang,Pang, Shaofeng,Su, Qiong,Wang, Yanbin,Xie, Xin,Zhang, Ping,Zhang, Yujing,Zhou, Feng
p. 1996 - 2010
(2020/04/07)

Rh/TiO2-Photocatalyzed Acceptorless Dehydrogenation of N-Heterocycles upon Visible-Light Illumination
TiO2 is an effective and extensively employed photocatalyst, but its practical use in visible-light-mediated organic synthesis is mainly hindered by its wide band gap energy. Herein, we have discovered that Rh-photodeposited TiO2 nanoparticles selectively dehydrogenate N-heterocyclic amines with the concomitant generation of molecular hydrogen gas in an inert atmosphere under visible light (λmax = 453 nm) illumination at room temperature. Initially, a visible-light-sensitive surface complex is formed between the N-heterocycle and TiO2. The acceptorless dehydrogenation of N-heterocycles is initiated by direct electron transfer from the HOMO energy level of the amine via the conduction band of TiO2 to the Rh nanoparticle. The reaction condition was optimized by examining different photodeposited noble metals on the surface of TiO2 and solvents, finding that Rh0 is the most efficient cocatalyst, and 2-propanol is the optimal solvent. Structurally diverse N-heterocycles such as tetrahydroquinolines, tetrahydroisoquinolines, indolines, and others bearing electron-deficient as well as electron-rich substituents underwent the dehydrogenation in good to excellent yields. The amount of released hydrogen gas evinces that only the N-heterocyclic amines are oxidized rather than the dispersant. This developed method demonstrates how UV-active TiO2 can be employed in visible-light-induced synthetic dehydrogenation of amines and simultaneous hydrogen storage applications.
Bahnemann, Detlef W.,Balayeva, Narmina O.,Dillert, Ralf,Mamiyev, Zamin,Zheng, Nan
p. 5542 - 5553
(2020/08/25)

Preparation method for (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline
The invention relates to a medical intermediate, in particular to a preparation method for (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. Benzoyl chloride or benzoic acid, phenylethylamine, alkali metalhydroxide and water are mixed to react, N-(2-phenethyl)benzamide, phosphorus pentoxide and phosphorus chloride at a certain ratio are mixed and heated with organic solvent, obtained 1-phenyl-3,4-dihydroisoquinoline, a first alcohol solvent and borohydride are mixed to react, the obtained 1-phenyl-1,2,3,4-dihydroisoquinoline, a second alcohol solvent, water and D-tartaric acid are mixed and heatedto react, the obtained (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline tartrate, alkali metal hydroxide and water are mixed to obtain a target product. The preparation method for (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline has the advantages of simpleness in operation and aftertreatment.
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(2019/03/31)

Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines
Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.
Nie, Huifang,Zhu, Yupu,Hu, Xiaomu,Wei, Zhao,Yao, Lin,Zhou, Gang,Wang, Pingan,Jiang, Ru,Zhang, Shengyong
p. 8641 - 8645
(2019/10/17)

Asymmetric Transfer Hydrogenation in Thermomorphic Microemulsions Based on Ionic Liquids
A thermomorphic ionic-liquid-based microemulsion system was successfully applied for the Ru-catalyzed asymmetric transfer hydrogenation of ketones. On the basis of the temperature-dependent multiphase behavior of the targeted microemulsion, simple product separation as well as catalyst recycling could be realized. The use of water-soluble ligands improved the immobilization of the catalyst in the microemulsion phase and significantly decreased the catalyst leaching into the organic layer upon extraction of the product. Eventually, the optimized microemulsion system could be applied to a wide range of aromatic ketones that were reduced with good isolated yields (up to 98%) and enantioselectivities (up to 97%), while aliphatic ketones were less successful.
Hejazifar, Mahtab,Pálv?lgyi, ádám Márk,Bitai, Jacqueline,Lanaridi, Olga,Bica-Schr?der, Katharina
p. 1841 - 1851
(2019/10/11)

Integrating Hydrogen Production with Aqueous Selective Semi-Dehydrogenation of Tetrahydroisoquinolines over a Ni2P Bifunctional Electrode
Exploring an alternative anodic reaction to produce value-added chemicals with high selectivity, especially integrated with promoted hydrogen generation, is desirable. Herein, a selective semi-dehydrogenation of tetrahydroisoquinolines (THIQs) is demonstrated to replace the oxygen evolution reaction (OER) for boosting H2 evolution reaction (HER) in water over a Ni2P nanosheet electrode. The value-added semi-dehydrogenation products, dihydroisoquinolines (DHIQs), can be selectively obtained with high yields at the anode. The controllable semi-dehydrogenation is attributed to the in situ formed NiII/NiIII redox active species. Such a strategy can deliver a variety of DHIQs bearing electron-withdrawing/donating groups in good yields and excellent selectivities, and can be applied to gram-scale synthesis. A two-electrode Ni2P bifunctional electrolyzer can produce both H2 and DHIQs with robust stability and high Faradaic efficiencies at a much lower cell voltage than that of overall water splitting.
Huang, Chenqi,Huang, Yi,Liu, Cuibo,Yu, Yifu,Zhang, Bin
supporting information
p. 12014 - 12017
(2019/08/07)

A Method for Bischler-Napieralski-Type Synthesis of 3,4-Dihydroisoquinolines
A new method for the Bischler-Napieralski-type synthesis of 3,4-dihydroisoquinolines was developed by a Tf2O-promoted tandem annulation from phenylethanols and nitriles. Its success was mainly due to the fact that a phenonium ion was formed in the process and practically functioned as a stable and reactive primary phenylethyl carbocation.
Min, Lin,Yang, Weiguang,Weng, Yunxiang,Zheng, Weiping,Wang, Xinyan,Hu, Yuefei
supporting information
p. 2574 - 2577
(2019/04/30)

Visible-Light-Mediated Photocatalytic Aerobic Dehydrogenation of N-heterocycles by Surface-Grafted TiO2 and 4-amino-TEMPO
Herein, the visible-light-induced dehydrogenation of N-heterocycles such as tetrahydroquinolines, tetrahydroisoquinolines, and indolines in O2-containing suspensions of a commercially available titanium dioxide photocatalyst yielding the corresponding heteroarenes is presented. 4-Amino-2,2,6,6-tetramethylpipiridinyloxyl (4-amino-TEMPO) was found to exhibit a beneficial role, as it increased the yield and improved the selectivity of the dehydrogenation reaction. Both the selectivity and the yield are further enhanced by grafting 0.1 wt % of Ni(II) ions onto the TiO2 surface. It is proposed that the basic reactant adsorbs at Lewis acid sites present at the TiO2 surface. The dehydrogenation reaction is initiated by visible-light excitation of the resulting surface complex and a subsequent single-electron transfer from the excited N-heterocycle via the conduction band of TiO2 to O2. Ni(II) ions possibly serve as an electron transfer bridge between the conduction band of TiO2 and O2, while the TEMPO derivative is assumed to act as a selective redox mediator involved in reactions of the generated reactive oxygen species.
Balayeva, Narmina O.,Zheng, Nan,Dillert, Ralf,Bahnemann, Detlef W.
p. 10694 - 10704
(2019/11/14)

Solifenacin succinate raw medicine synthesis process
The invention discloses a solifenacin succinate raw medicine synthesis process. 2-phenylethylamine and 3-quinuclidinone hydrochloride are respectively used as starting raw materials for synthesizing afragment A and a fragment B; then, condensation reaction occurs to generate solifenacin; through salt formation, the solifenacin succinate is obtained. The process is characterized in that straight-chain paraffin and water are used as reaction solvents; alkali metal hydroxides or carbonate and bicarbonates of the alkali metal hydroxides are used as acid-binding agents; phenylethylamine and benzoyl chloride take acylation reaction to generate midbodies 1 of solid precipitation fragments A insoluble in reaction solvents; in the post treatment process, filtering is directly performed; isomers ofthe fragment A are subjected to catalytic racemization through alkali metal hydroxides by using dimethylsulfoxide as a solvent, so that the byproduct isomers can be recovered and utilized; in the second-step reaction post treatment of the fragment B, a conventional pressure reduced distillation method is used for obtaining high-purity and high-yield 3-acetoxyquinine acetate. The invention provides a novel synthesis process with the advantages of high yield and economic and environment-friendly effects, and is suitable for industrial mass production.
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(2018/08/28)

Synthesis and characterization of S(-)1-phenyl-1,2,3,4-tetrahydro isoquinoline acetamide analogues
S(-)1-Phenyl-1,2,3,4-tetrahydro isoquinoline acetamide analogues are prepared by sequence of reactions which involve a metal hydride reduction of 3,4-dihydroisoquinoline followed by separation of S-form with mandelic acid (chiral reagent) by resolution. The product S(-)1-phenyl-1,2,3,4-tetrahydro isoquinoline is treated with halosubstituted acetyl chlorides to obtain tetrahydro isoquinoline acetyl chloride which is further employed to synthesize acetamide derivatives of tetrahydro isoquinoline using various substituted aryl amines. The products were characterized by advanced spectroscopic techniques.
Krishna Rao,Surendra Babu,Basaveswara Rao,Keshavi,Sundara Rao,Eswara Prasad,Murthy
p. 1035 - 1038
(2017/03/22)

Identification of an Imine Reductase for Asymmetric Reduction of Bulky Dihydroisoquinolines
A new imine reductase from Stackebrandtia nassauensis (SnIR) was identified, which displayed over 25- to 1400-fold greater catalytic efficiency for 1-methyl-3,4-dihydroisoquinoline (1-Me DHIQ) compared to other imine reductases reported. Subsequently, an efficient SnIR-catalyzed process was developed by simply optimizing the amount of cosolvent, and up to 15 g L-1 1-Me DHIQ was converted completely without a feeding strategy. Furthermore, the reaction proceeded well for a panel of dihydroisoquinolines, affording the corresponding tetrahydroisoquinolines (mostly in S-configuration) in good yields (up to 81%) and with moderate to excellent enantioselectivities (up to 99% ee).
Li, Hao,Tian, Ping,Xu, Jian-He,Zheng, Gao-Wei
p. 3151 - 3154
(2017/06/23)

Design, Synthesis, and Biological Evaluation of Tetrahydroisoquinoline-Based Histone Deacetylase 8 Selective Inhibitors
Histone deacetylase 8 (HDAC8) is a promising drug target for multiple therapeutic applications. Here, we describe the modeling, design, synthesis, and biological evaluation of a novel series of C1-substituted tetrahydroisoquinoline (TIQ)-based HDAC8 inhibitors. Minimization of entropic loss upon ligand binding and use of the unique HDAC8 "open" conformation of the binding site yielded a successful strategy for improvement of both HDAC8 potency and selectivity. The TIQ-based 3g and 3n exhibited the highest 82 and 55 nM HDAC8 potency and 330- and 135-fold selectivity over HDAC1, respectively. Selectivity over other class I isoforms was comparable or better, whereas inhibition of HDAC6, a class II HDAC isoform, was below 50% at 10 μM. The cytotoxicity of 3g and 3n was evaluated in neuroblastoma cell lines, and 3n displayed concentration-dependent cytotoxicity similar to or better than that of PCI-34051. The selectivity of 3g and 3n was confirmed in SH-SY5Y cells as both did not increase the acetylation of histone H3 and α-tubulin. Discovery of the novel TIQ chemotype paves the way for the development of HDAC8 selective inhibitors for therapeutic applications.
Taha, Taha Y.,Aboukhatwa, Shaimaa M.,Knopp, Rachel C.,Ikegaki, Naohiko,Abdelkarim, Hazem,Neerasa, Jayaprakash,Lu, Yunlong,Neelarapu, Raghupathi,Hanigan, Thomas W.,Thatcher, Gregory R. J.,Petukhov, Pavel A.
supporting information
p. 824 - 829
(2017/08/16)

Hybrid Catalysis Enabling Room-Temperature Hydrogen Gas Release from N-Heterocycles and Tetrahydronaphthalenes
Hybrid catalyst systems to achieve acceptorless dehydrogenation of N-heterocycles and tetrahydronaphthalenes-model substrates for liquid organic hydrogen carriers-were developed. A binary hybrid catalysis comprising an acridinium photoredox catalyst and a Pd metal catalyst was effective for the dehydrogenation of N-heterocycles, whereas a ternary hybrid catalysis comprising an acridinium photoredox catalyst, a Pd metal catalyst, and a thiophosphoric imide organocatalyst achieved dehydrogenation of tetrahydronaphthalenes. These hybrid catalyst systems allowed for 2 molar equiv of H2 gas release from six-membered N-heterocycles and tetrahydronaphthalenes under mild conditions, i.e., visible light irradiation at rt. The combined use of two or three different catalyst types was essential for the catalytic activity.
Kato, Shota,Saga, Yutaka,Kojima, Masahiro,Fuse, Hiromu,Matsunaga, Shigeki,Fukatsu, Arisa,Kondo, Mio,Masaoka, Shigeyuki,Kanai, Motomu
supporting information
p. 2204 - 2207
(2017/02/23)

One-Pot N-Deprotection and Catalytic Intramolecular Asymmetric Reductive Amination for the Synthesis of Tetrahydroisoquinolines
A one-pot N-Boc deprotection and catalytic intramolecular reductive amination protocol for the preparation of enantiomerically pure tetrahydroisoquinoline alkaloids is described. The iodine-bridged dimeric iridium complexes displayed superb stereoselectivity to give tetrahydroisoquinolines, including several key pharmaceutical drug intermediates, in excellent yields under mild reaction conditions. Three additives played important roles in this reaction: Titanium(IV) isopropoxide and molecular iodine accelerated the transformation of the intermediate imine to the tetrahydroisoquinoline product; p-toluenesulfonic acid contributed to the stereocontrol.
Zhou, Huan,Liu, Yuan,Yang, Suhua,Zhou, Le,Chang, Mingxin
supporting information
p. 2725 - 2729
(2017/02/26)

Method for solvent accelerated selective dehydrogenation of tetrahydroisoquinoline type compound
The invention discloses a method for synthesizing 1-substituted-3,4-dihydroisoquinoline through the solvent accelerated selective partial dehydrogenation of a 1-substituted-1,2,3,4-tetrahydroisoquinoline compound. For a simple and easily obtained cyclic amine type compound such as a tetrahydroisoquinoline compound, a corresponding imine compound can be obtained through selective dehydrogenation; the conversion ratio of the cyclic amine type compound is higher; further, the proportion of a partially dehydrogenated product to a fully dehydrogenated product is more than 20 to 1. The method is simple and convenient to operate, is practical, easy and feasible, and is mild in reaction condition; the actual cost is greatly reduced. In addition, a method for synthesizing 3,4-dihydroisoquinoline through the direct dehydrogenation of tetrahydroisoquinoline has the advantages of atom economy and environmental friendliness.
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Paragraph 0033; 0034; 0035; 0036; 0037; 0038; 0029-0043

(2017/07/22)

Dehydrogenation of Nitrogen Heterocycles Using Graphene Oxide as a Versatile Metal-Free Catalyst under Air
Graphene oxide (GO) has been developed as an inexpensive, environmental friendly, metal-free carbocatalyst for the dehydrogenation of nitrogen heterocycles. Valuable compounds, such as quinoline, 3,4-dihydroisoquinoline, quinazoline, and indole derivatives, have been successfully used as substrates. The investigation of various oxygen-containing molecules with different conjugated systems indicated that both the oxygen-containing groups and large π-conjugated system in GO sheets are essential for this reaction. (Figure presented.).
Zhang, Jingyu,Chen, Shiya,Chen, Fangfang,Xu, Wensheng,Deng, Guo-Jun,Gong, Hang
supporting information
p. 2358 - 2363
(2017/07/22)

1-phenyl -1, 2, 3, 4-isoquinoline method for the preparation of
The invention provides a 1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline preparation method. The 1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline preparation method comprises the following steps of: mixing benzoyl chloride or benzoic acid, phenethylamine and alkali metal hydroxide with water, and reacting to obtain N-(2-phenethyl) benzamide; then mixing the N-(2-phenethyl) benzamide with phosphorus pentoxide, chloride phosphorus and a benzene solvent, heating and reacting to obtain 1-phenyl-3, 4-dihydro-isoquinoline; and further mixing the 1-phenyl-3, 4-dihydro-isoquinoline with a first alcohol solvent and hydroboron, and reacting to obtain the product. Compared with the prior art, the 1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline preparation method has the advantages that firstly, no organic solvents are added, the product N-(2-phenethyl) benzamide is insoluble in an aqueous solution, and therefore, the steps of skimming and the like are avoided in the after-treatment process, and the after-treatment operation is simplified; secondarily, as the organic solvents are not added, the cost is reduced, and the pollution to environments is avoided; and thirdly, as the phosphorus pentoxide and the chloride phosphorus are subjected to oxidization cyclization reaction, polyphosphoric acids are prevented from being heated and decomposed to generate hypertoxic phosphorus oxide exhaust gas.
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(2017/01/26)

Enantioselective, Copper-Catalyzed Alkynylation of Ketimines to Deliver Isoquinolines with α-Diaryl Tetrasubstituted Stereocenters
An enantioselective, copper-catalyzed alkynylation of cyclic α,α-diaryl ketiminium ions has been developed to deliver isoquinoline products with diaryl, tetrasubstituted stereocenters. The success of this reaction relied on identification of Ph-PyBox as the optimal ligand, i-Pr2NEt as the base, and CHCl3 as the solvent. A broad scope and functional group tolerance were observed. Notably, the use of both aryl and silyl acetylenes results in high yields and enantioselectivities. Mechanistic experiments are consistent with a dimeric or higher order catalyst.
Dasgupta, Srimoyee,Liu, Jixin,Shoffler, Clarissa A.,Yap, Glenn P. A.,Watson, Mary P.
supporting information
p. 6006 - 6009
(2016/12/09)

Method for preparing solifenacin intermediate
The invention belongs to the field of medicine and particularly relates to a method for preparing a solifenacin intermediate. After 2-halogenated diphenyl ketone is used for carbonyl protection, n-butyllithium is used for removing bromine, then the formyl group is added; a condensation reaction with nitromethane and catalytic hydrogenation for reduction are carried out, and then acidification is conducted; later, cyclization is carried out, and a solifenacin intermediate compound I is obtained through alkaline hydrolysis after reduction and chiral resolution. The structural formula of the solifenacin intermediate is shown in the description. According to the method for preparing the solifenacin intermediate, the initial raw materials easy to obtain are utilized, and the production cost is reduced. The process route is advanced, the reaction conditions are mild, the reaction yield is high, less three wastes are caused, expensive and toxic reagents do not exist, reaction solvents can be used repeatedly after distillation, industrial production is facilitated, and implementation value and social, economic and environmental protection benefits are high.
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(2016/11/24)

Palladium carbon catalyzed selective partial dehydrogenation method of tetrahydroisoquinoline
The invention relates to a method for synthesis of 1-substituted-3, 4-dihydroisoquinoline by palladium carbon catalyzed selective partial dehydrogenation of a 1-substituted-1, 2, 3, 4-tetrahydroisoquinoline compound. The reaction temperature is 0-80DEG C. For easily available cyclic amine compounds like tetrahydroisoquinoline, a corresponding imine compound can be obtained through selective dehydrogenation, the conversion rate is up to 99%, and the proportion of a partial dehydrogenation product and a complete dehydrogenation product is greater than 20:1. The method provided by the invention has simple and practical operation, the raw materials and catalyst are cheap and easily available, the reaction conditions are mild, and the catalyst can be recycled, thus greatly reducing the actual cost. In addition, the method for synthesis of 3, 4-dihydroisoquinoline through direct dehydrogenation of tetrahydroisoquinoline has the advantages of atom economy and environmental friendliness.
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Paragraph 0036; 0037; 0040

(2017/02/09)

Solvent-promoted highly selective dehydrogenation of tetrahydroisoquinolines without catalyst and hydrogen acceptor
An unusual solvent DMF-promoted dehydrogenation of 1-substituted 1,2,3,4-tetrahydroisoquinolines to synthesize cyclic imines is described. This environmentally friendly reaction features no requirement of any metal catalysts, oxidants, or hydrogen acceptors. A wide range of structurally varied 3,4-dihydroisoquinolines can be obtained with good yields and excellent chemoselectivities.
Feng, Guang-Shou,Ji, Yue,Liu, Hui-Fang,Shi, Lei,Zhou, Yong-Gui
supporting information
p. 747 - 749
(2016/02/05)

A Titanium(III)-Catalyzed Reductive Umpolung Reaction for the Synthesis of 1,1-Disubstituted Tetrahydroisoquinolines
A catalytic reductive C1-acylation of 3,4-dihydroisoquinolines is presented that gives direct access to 1,1-disubstituted tetrahydroisoquinolines. The reaction is a titanium(III)-catalyzed reductive umpolung process in which nitriles act as effective acylation agents. The method is highly chemo- and regioselective and is demonstrated in 20 examples. It is well-suited for the large-scale synthesis of functionalized tetrahydroisoquinoline products, which is exemplified in the form of a six-step synthesis of (±)-3-demethoxyerythratidinone. (Figure Presented).
Luu, Hieu-Trinh,Wiesler, Stefan,Frey, Georg,Streuff, Jan
p. 2478 - 2481
(2015/05/27)

Enantioselective Synthesis of 1-Aryl-Substituted Tetrahydroisoquinolines Through Ru-Catalyzed Asymmetric Transfer Hydrogenation
A convenient and general asymmetric transfer hydrogenation of a wide array of 1-aryl-3,4-dihydroisoquinoline derivatives using a [RuIICl(η6-benzene)TsDPEN] complex in combination with a 5:2 HCOOH-Et3N azeotropic mixture as a hydrogen source was developed. Under mild reaction conditions, the described catalytic transformation secured a practical synthetic access to the corresponding valuable chiral 1-aryltetrahydroisoquinoline units with high atom economy, a broad substrate scope, high isolated yields (up to 97%) and good to excellent enantioselectivities (up to 99% ee). It was found that the stereochemical outcome of the reaction was strongly influenced by both the structure of the catalyst and the substituents present on the substrate. The synthetic utility of the present protocol has been demonstrated through the asymmetric synthesis of several biologically important alkaloids including the antiepileptic drug agent 1c, as well as (-)-nor-cryptostyline alkaloids I and II.
Perez, Marc,Wu, Zi,Scalone, Michelangelo,Ayad, Tahar,Ratovelomanana-Vidal, Virginie
p. 6503 - 6514
(2015/10/19)

Compounds with cardiac myosin activating function and pharmaceutical composition containing the same for treating or preventing heart failure
Disclosed are a compound having cardiotonic activity and a pharmaceutical composition containing the same, and the composition containing the compound, according to the present invention, is useful for preventing and treating heart failure.COPYRIGHT KIPO 2016
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(2016/10/07)

Highly selective partial dehydrogenation of tetrahydroisoquinolines using modified Pd/C
A highly selective procedure has been developed for the partial dehydrogenation of 1-substituted-1,2,3,4-tetrahydroisoquinolines over K3PO4·3H2O-modified Pd/C catalyst. This new method provides facile, atom-economical and environmentally friendly access to 1-substituted-3,4-dihydroisoquinolines without the need for stoichiometric amounts of harmful oxidants. The use of standard Pd/C as a catalyst for this process gave poor chemoselectivity. Pleasingly, the use of a K3PO4·3H2O-modified Pd/C catalyst promoted the partial dehydrogenation of 1-substituted-1,2,3,4-tetrahydroisoquinolines with excellent chemoselectivity by suppressing further dehydroaromatization. Furthermore, conducting the reaction under an atmosphere of oxygen led to further improvements in the chemoselectivity of the dehydrogenation, with the ratio of imine to isoquinoline reaching up to 32/1. The heterogenous Pd/C catalyst could also be recycled and reused at least three times with excellent conversion and chemoselectivity, demonstrating the significantly practical potential of this methodology.
Ji, Yue,Chen, Mu-Wang,Shi, Lei,Zhou, Yong-Gui
p. 33 - 39
(2015/09/28)

New synthetic approach for the preparation of 1-Aryl-3,4-dihydroisoquinolines by liebeskind-srogl reaction
An efficient synthetic methodology has been developed to construct 1-aryl-3,4-dihydroisoquinoline derivatives. The reaction was performed under neutral conditions by a palladium-catalyzed desulfitative carbon-carbon cross-coupling protocol.
ábrányi-Balogh, Péter,Slégel, Péter,Volk, Balázs,Pongó, László,Milen, Mátyás
p. 2574 - 2578
(2015/01/09)

One-pot racemization process of 1-Phenyl-1,2,3,4-tetrahydroisoquinoline: A key intermediate for the antimuscarinic agent solifenacin
(S)-(+)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline, which is the key intermediate in preparing the urinary antispasmodic drug solifenacin, was racemized in quantitative yield by a simple one-pot procedure through N-chlorination with trichloroisocyanuric acid, conversion of the N-chloroamine into the imine hydrochloride, and reduction of the imine double bond. The racemized amine was successfully resolved by d-(-)-tartaric acid obtaining (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline in 81% yield and with 96.7% ee and, from the crystallization mother liquors, the R enriched form. This was racemized by the same one-pot process and resolved by d-(-)-tartaric acid with the same efficiency. Such an approach to the racemization of 1-phenyl-1,2,3,4- tetrahydroisoquinoline can be industrially useful to recycle the waste R enantiomer resulting from the classical resolution used to obtain the S enantiomer on a large scale.
Bolchi, Cristiano,Pallavicini, Marco,Fumagalli, Laura,Straniero, Valentina,Valoti, Ermanno
p. 432 - 437
(2013/05/09)

Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products
The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine.
Ghislieri, Diego,Green, Anthony P.,Pontini, Marta,Willies, Simon C.,Rowles, Ian,Frank, Annika,Grogan, Gideon,Turner, Nicholas J.
p. 10863 - 10869
(2013/08/23)

Ionic liquids-assisted synthesis of 3,4-dihydroisoquinolines by the Bishler-Napieralski reaction
The Bishler-Napieralski cyclodehydration of N-acyl-2-arylethylamines into the corresponding 3,4-dihydroisoquinolines with POCl3 as a dehydration reagent proceeds in ionic liquids under milder conditions and in higher yields.
Epishina, Margarita A.,Kulikov, Alexander S.,Struchkova, Marina I.,Ignat'Ev, Nikolai V.,Schulte, Michael,Makhova, Nina N.
p. 267 - 269
(2013/01/15)

Mild and efficient syntheses of 1-aryl-3,4-dihydroisoquinolines and 1-aryl-3,4-dihydro-β-carbolines via regiospecific β-eliminations of the corresponding N-tosyl-1,2,3,4-tetrahydroisoquinolines and N-tosyl-1,2,3,4-tetrahydro-β-carbolines
(Chemical Equation Presented) Treatment of N-tosyl-1-aryl-1,2,3,4- tetrahydro-isoquinolines or N-tosyl-1-aryl-1, 2,3,4-tetrahydro-β-carbolines with a strong base such as NaOH or KOH at 70 °C in dimethylsulfoxide (DMSO) produced 1-aryl-3,4-dihydroisoquinolines or 1-aryl-3,4-dihydro-β- carbolines in good yields via mild and regiospecific β-eliminations. A dramatic solvent effect was observed, DMSO was crucial for the reactions. The temperature is also crucial for the reactions and should be kept between 60 and 80 °C. Copyright Taylor & Francis Group, LLC.
Dong, Jing,Shi, Xiao-Xin,Xing, Jing,Yan, Jing-Jing
experimental part
p. 2806 - 2817
(2012/07/16)

A highly efficient and enantioselective access to tetrahydroisoquinoline alkaloids: Asymmetric hydrogenation with an iridium catalyst
Efficient and enantioselective: Using the iodine-bridged dimeric iridium complex [{Ir(H)[(S,S)-(f)-binaphane]}2(μ-I)3] +I- (1) a wide range of tetrahydroisoquinoline alkaloids, including the substructure of the pharmaceutical drug solifenacin, were obtained with excellent enantioselectivities and high turnover numbers (see scheme). Copyright
Chang, Mingxin,Li, Wei,Zhang, Xumu
p. 10679 - 10681
(2011/12/05)

Efficient and practical one-pot conversions of n- tosyltetrahydroisoquinolines into isoquinolines and of N-tosyltetrahydro-β- carbolines into β-carbolines through tandem β-elimination and aromatization
An efficient, practical, and general method for conversions of N-tosyltetrahydroisoquinolines (N-tosyl-THIQs) into isoquinolines and of N-tosyltetrahydro-β-carbolines (N-tosyl-THBCs) into β-carbolines is described. Treatment of N-tosyl-THIQs or N-tosyl-THBCs with base in dimethyl sulfoxide afforded dihydroisoquinolines or dihydro-β-carbolines as intermediates, and these were then oxidized in situ by molecular oxygen to furnish isoquinolines or β-carbolines in good to high yields. Both one-pot conversions occurred through tandem β-elimination and aromatization. An efficient method for conversions ofN-tosyltetrahydroisoquinolines (N-tosyl-THIQs) and N-tosyltetrahydro-β-carbolines (N-tosyl-THBCs) into isoquinolines and β-carbolines is described. Treatment ofN-tosyl-THIQs or N-tosyl-THBCs with base affords dihydroisoquinolines or dihydro-β- carbolines. These can be oxidized in situ by molecular oxygen to furnish isoquinolines or β-carbolines. Copyright
Dong, Jing,Shi, Xiao-Xin,Yan, Jing-Jing,Xing, Jing,Zhang, Qiang,Xiao, Sen
body text
p. 6987 - 6992
(2011/02/24)

A versatile cyclodehydration reaction for the synthesis of isoquinoline and β-carboline derivatives
(Chemical Equation Presented) The direct conversion of various amides to isoquinoline and β-carboline derivatives via mild electrophilic amide activation, with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine, is described. Low-temperature amide activation followed by cyclodehydration upon warming provides the desired products with short overall reaction times. The successful use of nonactivated and halogenated phenethylene derived amides, N-vinyl amides, and optically active substrates is noteworthy.
Movassaghi, Mohammad,Hill, Matthew D.
supporting information; experimental part
p. 3485 - 3488
(2009/05/07)

SOLIFENACIN COMPOSITIONS
Compositions and/or formulations comprising solifenacin or a salt thereof and processes for preparing the same. Certain compositions and formulations contain a stable amorphous form of solifenacin succinate.
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(2008/12/08)

Synthesis of benzoazocines from substituted tetrahydroisoquinolines and activated alkynes in a tetrahydropyridine ring expansion
Tetrahydroisoquinolines underwent tandem piperidine ring enlargement in the presence of activated alkynes in acetonitrile or methanol, producing tetrahydrobenzo[d]azocines in high yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
Voskressensky, Leonid G.,Listratova, Anna V.,Borisova, Tatiana N.,Alexandrov, Grigoriy G.,Varlamov, Alexey V.
p. 6106 - 6117
(2008/09/17)

New iridium complex as high-efficiency red phosphorescent emitter in polymer light-emitting devices
A new heteroleptic iridium complex Ir(1-piq)2pt with 1-phenylisoquinoline and 3-(pyridin-2′-yl)-1H-1,2,4-triazole was synthesized and characterized. The complex was incorporated into phosphorescent polymer light-emitting devices using polyhedral oligomeric silsesquioxane- terminated polyfluorene (PFO-poss) as a host polymer doped with 30% of electron transport materials 2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole (PBD). Red electrophosphorescence was observed with a peak emission at 605 nm. The highest-efficiency polymer light-emitting diode was achieved with PFO-poss doped with 2% Ir(1-piq)2pt. An external quantum efficiency of 10.4% and a luminous efficiency of 9.4 cd A-1 were obtained at 10.8 mA cm-2. These values were found to be 7.67% and 5.99 cd A-1 at 100 mA cm-2.
Liang, Bo,Jiang, Changyun,Chen, Zhao,Zhang, Xiuju,Shi, Huahong,Cao, Yong
p. 1281 - 1286
(2007/10/03)

Tandem enlargement of the tetrahydropyridine ring in 1-aryl-tetrahydroisoquinolines using activated alkynes-a new and effective synthesis of benzoazocines
Tetrahydroisoquinolines 3a-e underwent piperidine ring enlargement under the action of activated alkynes, giving benzoazocines 4, 5 and 7-11 in high yields.
Voskressensky, Leonid G.,Borisova, Tatiana N.,Listratova, Anna V.,Kulikova, Larisa N.,Titov, Alexander A.,Varlamov, Alexey V.
p. 4585 - 4589
(2007/10/03)

3,4-DIHYDROISOQUINOLINE COMPOUNDS AS MUSCRINIC RECEPTOR ANTAGONISTS FOR THE TREATMENT OF RESPIRATORY, URINARY AND GASTROINTESTINAL DISEASES
The present invention generally relates to muscarinic receptor antagonists of formula (I), which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds, and the methods for treating diseases mediated through muscarinic receptors. Formula (I) wherein Formula (II) represents a nitrogen-containing ring having from 5 to 9 carbon atoms is a bridging group selected from the group consisting of -(CH2)n-, -CH(Q)CH2-, -CH2CH(Q)CH2-, -CH2-O-CH2- or -CH2-NH-CH2-), where n is an integer selected from 0-3 (wherein when n is zero then T represents a direct bond); Y is alkylene, alkenylene, alkynylene or no atom; X is -NH or oxygen.
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Page/Page column 21

(2010/10/20)

Synthesis and antimuscarinic properties of quinuclidin-3-yl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives as novel muscarinic receptor antagonists
In the course of continuing efforts to develop potent and bladder-selective muscarinic M3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4- tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-l,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.
Naito, Ryo,Yonetoku, Yasuhiro,Okamoto, Yoshinori,Toyoshima, Akira,Ikeda, Ken,Takeuchi, Makoto
p. 6597 - 6606
(2007/10/03)

Synthesis of a high-efficiency red phosphorescent emitter for organic light-emitting diodes
Four novel red phosphorescent emitter compounds bis(1-phenylisoquinolinato- N,C2′)iridium(acetylacetonate), (piq)2Ir(acac), bis(1-(1′-naphthyl)isoquinolinato-N,C2′) iridium(acetylacetonate), (1-niq)2Ir(acac), bis(1-(2′-naphthyl) isoquinolinato-N,C2′)iridium(acetylacetonate), (2-niq) 2Ir(acac) and bis(1-phenyl-5-methylisoquinolinato-N,C 2′)iridium(acetylacetonate), (m-piq)2Ir(acac), have been synthesized and fully characterized. Electroluminescent devices with a configuration of ITO/NPB/CBP:dopant/BCP/AlQ3/Al were fabricated. All devices emitted in the red region with an emission ranging from 624 to 680 nm. (m-piq)2Ir(acac) shows a maximum brightness of 17 164 cd m -2 at a current density of J = 300 mA cm-2 and the best luminance efficiency of 8.91 cd A-1 at a current density of J = 20 mA cm-2. (1-niq)2Ir(acac) exhibits pure-red emission with 1931 CIE (Commission International de L'Eclairage) chromaticity coordinates x = 0.701, y = 0.273.
Yang, Cheng-Hsien,Tai, Chia-Cheng,Sun, I.-Wen
p. 947 - 950
(2007/10/03)

Design, synthesis, and inhibition of platelet aggregation for some 1-o-chlorophenyl-1,2,3,4-tetrahydroisoquinoline derivatives
Four analogs proved to be potential antiplatelet aggregation agents, and compound 9 (TQP-3, applying for patent), which inhibits ADP-induced human platelet aggregation with IC50 values of approximately 0.206 nM was the most active. Based on ticlopidine active as an ADP receptor antagonist for inhibiting platelet aggregation in clinical test, and upon finding (±)-1,2-substituted-7-sulfonylamide/amide-1,2,3,4-tetrahydroisoquinoline (11-31) inhibited of platelet aggregation, a series of (±)-1-o- chlorophenyl-2-substituted-tetrahydroisoquinoline derivatives was designed and synthesized. Four analogs proved to be potential antiplatelet aggregation agents, and compound 9 (TQP-3, applying for patent) which inhibits ADP-induced human platelet aggregation with IC50 values of approximately 0.206 nM was the most active. Compound 2 is more active than compound 1, which (Type I) is similar to ticlopidine. This is because there is a spacial hindrance in compound 1, and the o-chloro group of compound 2 may play the same a role as o-chloro group of ticlopidine. On the other hand, with the different substitutions at different positions on the 2-substituted phenylacyl group, their inhibition of platelet aggregation differs. These compounds with m-substituted group (5, 7, 9) showed a higher IC50 value for inhibiting ADP-induced human platelet aggregation than those with o-substituted group (4, 6) or p-substituted group (3, 8). It was observed that their inhibition is bromine-substituted derivative (9), chlorine-substituted derivative (7), and nitro-substituted derivative (5) in turn. Moreover, these compounds (Type II) may be more similar to clopidogrel than to ticlopidine due to the acyl group at 2 position of the nucleus playing a role as the ester group of clopidogrel. It was conjectured that these analogs function as a potential antiplatelet aggregation role by acting as ADP receptor antagonists.
Yang, Jie,Hua, Wei-Yi,Wang, Fu-Xiang,Wang, Zhi-Yuan,Wang, Xiang
p. 6547 - 6557
(2007/10/03)

OXIDATION OF 1,2,3,4-TETRAHYDROISOQUINOLINES TO 3,4-DIHYDROISOQUINOLINES WITH MOLECULAR OXYGEN CATALYZED BY COPPER(II) CHLORIDE
A catalytic oxidation system, a CuCl2-O2 system, was efficient for dehydrogenation of 1,2,3,4-tetrahydroisoquinolines to 3,4-dihydroquinolines.Oxidation of 1,2,3,4-tetrahydroquinoline was also carried out.
Shimizu, Masao,Orita, Hideo,Hayakawa, Takashi,Suzuki, Kunio,Takehira, Katsuomi
p. 773 - 780
(2007/10/02)

Microwave-Induced Organic Reaction Enhancement Chemistry. 2. Simplified Techniques
A variety of organic reactions have been conducted efficiently in a few minutes in unsealed vessels at ambient pressure in unmodified microwave ovens by using selected organic solvents.
Bose, Ajay K.,Manhas, Maghar S.,Ghosh, Malay,Shah, Mamta,Raju, Vegesna S.,et al.
p. 6968 - 6970
(2007/10/02)

HIGHLY ACCELERATED REACTIONS IN A MICROWAVE OVEN : SYNTHESIS OF HETEROCYCLES
Efficient synthesis of a wide variety of heterocycles on 0.1 to 200 g scale was conducted in organic solvents in a commercial microwave oven in a few minutes at a low energy level.Erlenmeyer flasks were adequate reaction vessels since neither high pressure nor high temperature were involved.Fast monitoring of synthetic reactions was achieved by tlc separation and transfer of tlc spot material directly to a solids probe of a chemical ionization mass spectrometer.Microwave Oven-induced Reaction Enhancement (MORE) chemistry is not due to thermolysis: one reaction was conducted successfully in a reaction vial encased in a block of ice.
Bose, Ajay K.,Manhas, Maghar S.,Ghosh, Malay,Raju, Vegesna S.,Tabei, Keiko,Urbanczyk-Lipkowska, Zofia
p. 741 - 744
(2007/10/02)

Phencyclidine-like Effects of Tetrahydroisoquinolines and Related Compounds
A series of 1,2,3,4-tetrahydroisoquinolines, tetrahydrothienopyridines, and related compounds were evaluated for their ability to inhibit binding of -1--N-allylnormetazocine to phencyclidine (PCP) and ? receptors, respectively.A representative series of compounds was evaluated in behavioral assays to determine the ability of the compounds to induce PCP-like stereotyped behavior and ataxia.All of the compounds caused stereotyped behavior and ataxia, indicating their agonist actions at the PCP site.
Gray, Nancy M.,Cheng, Brian K.,Mick, Stephen J.,Lair, Cecelia M.,Contreras, Patricia C.
p. 1242 - 1248
(2007/10/02)