- Development of Scaled-Up Synthetic Method for Retinoid X Receptor Agonist NEt-3IB Contributing to Sustainable Development Goals
-
Small-molecular drugs, which are generally inexpensive compared with biopharmaceuticals and can often be taken orally, may contribute to the Sustainable Development Goals (SDGs) adopted by the United Nations. We previously reported the retinoid X receptor (RXR) agonist 4-(ethyl(3-isobutoxy-4-isopropyl-phenyl)amino)benzoic acid (NEt-3IB, 1) as a small-molecular drug candidate to replace biopharmaceuticals for the treatment of inflammatory bowel disease. The previous synthetic method to 1 required a large amount of organic solvent and extensive purification. In line with the SDGs, we aimed to develop an environmentally friendly, inexpensive method for the large-scale synthesis of 1. The developed method requires only a hydrophobic ether and EtOH as reaction and extraction solvents. The product was purified by recrystallization twice to afford 99% pure 1 at 100mmol scale in about 30% yield. The optimized process showed a 35-fold improvement of the E-factor (an index of environmental impact) compared to the original method. This work, which changes the solvent used to environmentally preferable ones based on the existing synthetic method for 1, illustrates how synthetic methods for small-molecular drugs can be adapted and improved to contribute to the SDGs.
- Kakuta, Hiroki,Kikuzawa, Shota,Morishita, Ken-Ichi,Takamura, Yuta,Watanabe, Masaki
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p. 146 - 154
(2022/02/05)
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- Photoinduced Iron-Catalyzed ipso-Nitration of Aryl Halides via Single-Electron Transfer
-
A photoinduced iron-catalyzed ipso-nitration of aryl halides with KNO2 has been developed, in which aryl iodides, bromides, and some of aryl chlorides are feasible. The mechanism investigations show that the in situ formed iron complex by FeSO4, KNO2, and 1,10-phenanthroline acts as the light-harvesting photocatalyst with a longer lifetime of the excited state, and the reaction undergoes a photoinduced single-electron transfer (SET) process. This work represents an example for the photoinduced iron-catalyzed Ullmann-type couplings.
- Wu, Cunluo,Bian, Qilong,Ding, Tao,Tang, Mingming,Zhang, Wenkai,Xu, Yuanqing,Liu, Baoying,Xu, Hao,Li, Hai-Bei,Fu, Hua
-
p. 9561 - 9568
(2021/08/06)
-
- Halogen-Bridged Methylnaphthyl Palladium Dimers as Versatile Catalyst Precursors in Coupling Reactions
-
Halogen-bridged methylnaphthyl (MeNAP) palladium dimers are presented as multipurpose Pd-precursors, ideally suited for catalytic method development and preparative organic synthesis. By simply mixing with phosphine or carbene ligands, they are in situ converted into well-defined monoligated complexes. Their catalytic performance was benchmarked against state-of-the-art systems in challenging Buchwald–Hartwig, Heck, Suzuki and Negishi couplings, and ketone arylations. Their use enabled record-setting activities, beyond those achievable by optimization of the ligand alone. The MeNAP catalysts permit syntheses of tetra-ortho-substituted arenes and bulky anilines in near-quantitative yields at room temperature, allow mono-arylations of small ketones, and enable so far elusive cross-couplings of secondary alkyl boronic acids with aryl chlorides.
- Doppiu, Angelino,Goo?en, Lukas J.,Hu, Zhiyong,Pirkl, Nico,Sivendran, Nardana
-
supporting information
p. 25151 - 25160
(2021/10/19)
-
- Selective hydrogenation of nitroarenes under mild conditions by the optimization of active sites in a well defined Co?NC catalyst
-
The catalytic hydrogenation of aromatic nitro compounds containing multiple functional groups into amino compounds with high conversion rates, selectivity, and stability under mild conditions is a great challenge. Herein, a well defined catalyst (Co?NC) is prepared through the pyrolysis of the Co-centered metal-organic framework (MOF) at the optimized temperature. The as-synthesized catalyst exhibits a high conversion rate and selectivity for the hydrogenation of 12 aromatic nitro compounds with different competing groups into desired amino compounds with hydrazine hydrate under mild conditions (80 °C, 30 min, and 1 atm). The catalyst also shows excellent stability and can be reused over 20 times without considerably losing its activity. It is found that the Co-Nx site is the main active site for catalytic hydrogenation, and the Mott-Schottky effect between the surface Co NPs and N-doped carbon can further promote the hydrogenation reaction. EXAFS, TEM, XPS, and Raman analyses confirm that cobalt nanoparticles (NPs) are properly encapsulated by the N-doped carbon matrix at the optimized temperature, and the Co species maintain a high spin state after the catalysis, which may be responsible for the high performance of Co?NC. This work demonstrates not only a highly efficient catalyst for hydrogenation under mild conditions, but also provides insight into the active sites in Co-based catalysts for hydrogenation.
- Chen, Shuo,Jiang, Hong,Jiang, Shun-Feng,Ling, Li-Li
-
supporting information
p. 5730 - 5741
(2020/09/21)
-
- Base promoted peroxide systems for the efficient synthesis of nitroarenes and benzamides
-
A useful and efficient approach for the synthesis of nitroarenes from several aromatic amines (including heterocycles) using peroxide and base has been developed. This oxidative reaction is very easy to handle and afforded the products in good yields. Formation of benzamides from benzylamine was also successfully carried out with this metal-free catalytic system in good to excellent yields.
- Gupta, Sampa,Ansari, Alisha,Sashidhara, Koneni V.
-
supporting information
(2019/09/07)
-
- Telescoped Sequence of Exothermic and Endothermic Reactions in Multistep Flow Synthesis
-
A multistep sequential flow synthesis of isopropyl phenol is demonstrated, involving 4-step exothermic, endothermic, and temperature sensitive reactions such as nitration, reduction, diazotization, and high temperature hydrolysis. Nitration of cumene with fuming nitric acid produces 2- A nd 4-nitrocumene which are converted into respective cumidines by the hydrogenation using Pd/Ni catalyst in H-cube with gravity separation. Hydrolysis of in situ generated diazonium salts in the boiling acidic conditions is carried out using integration of flow and microwave-assisted synthesis. 58% of 4-isopropyl phenol was obtained. The sequential flow synthesis can be applied to synthesize other organic compounds involving this specific sequence of reactions.
- Sharma, Yachita,Nikam, Arun V.,Kulkarni, Amol A.
-
p. 170 - 176
(2019/02/01)
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- Regioselective mononitration of aromatic compounds with N2O5 by acidic ionic liquids via continuous flow microreactor
-
We employed N2O5 as highly active nitrating reagents and a host of acidic ionic liquid as catalysts in these reactions which were conducted in a continuous flow microreactor. When we utilized PEG400-DAIL as catalysts, the conversion of toluene was increased to 95.5 % and the yield of mononitration product (o/p ratio reached 1.10) significantly improved to 99 %, meanwhile the reaction time was drastically shortened to 1/120 of the conventional reactor. Nitration in ionic liquids was surveyed using a host of aromatic substrates with similar reactivity. The ionic liquid recycling procedures had also been devised.
- Liu, Jianhua,Li, Bindong,Wang, Huan
-
p. 513 - 516
(2016/01/20)
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- Stereospecific Pd-catalyzed cross-coupling reactions of secondary alkylboron nucleophiles and aryl chlorides
-
We report the development of a Pd-catalyzed process for the stereospecific cross-coupling of unactivated secondary alkylboron nucleophiles and aryl chlorides. This process tolerates the use of secondary alkylboronic acids and secondary alkyltrifluoroborates and occurs without significant isomerization of the alkyl nucelophile. Optically active secondary alkyltrifluoroborate reagents undergo cross-coupling reactions with stereospecific inversion of configuration using this method.
- Li, Ling,Zhao, Shibin,Joshi-Pangu, Amruta,Diane, Mohamed,Biscoe, Mark R.
-
supporting information
p. 14027 - 14030
(2015/01/08)
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- Bismuth triflate catalyzed mononitration of aromatic compounds with N 2O5
-
This page isvestigated that bismuth triflate catalysed the nitration of a range of simple aromatic compounds in good to excellent yields at 0-30 °C within 2 h using N2O5 and the catalyst can be recycled without apparent loss of activity. Mechanistic insights demonstrate that triflic acid is generated and that, at least, when two competing catalytic cycles are operating at the same time: a rapid one involving triflic acid and a slower one involving the bismuth triflate.
- Qian, Hua,Wang, Ya,Liu, Dabin,Lv, Chunxu
-
p. 509 - 512
(2014/05/20)
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- Efficient ipso-nitration of arylboronic acids with iron nitrate as the nitro source
-
A novel, simple and efficient ipso-nitration of arylboronic acids with iron nitrate has been developed. The protocol uses readily available arylboronic acids as the starting materials, inexpensive iron nitrate (0.5 equiv.) as the nitro source without addition of an additive, and the corresponding nitroarenes were obtained in good to excellent yields.
- Jiang, Min,Yang, Haijun,Li, Yong,Jia, Zhiying,Fu, Hua
-
p. 25602 - 25604
(2013/12/04)
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- Reusable and efficient polystryrene-supported acidic ionic liquid catalyst for mononitration of aromatic compounds
-
A series of polystyrene-supported 1-(propyl-3-sulfonate)-3-methyl- imidazolium hydrosulfate acidic ionic liquid (PS-[SO3H-PMIM][HSO 4]) catalysts were prepared and tested for mononitration of simple aromatics compounds with nitric acid. It was found that the reactivity of the catalysts increased with increasing [SO3HPMIM][ HSO4] content. The para-selectivity was not only related to the [SO 3H-PMIM][HSO4] content but also the substituent groups in aromatics. A reaction mechanism of nitration over this new catalyst was proposed. The catalytic activity of this catalyst decreased slightly after fifth runs in the synthesis of nitrotoluene.
- Li, Li Xia,Ling, Qi Long,Liu, Zu Liang,Xing, Xiao Dong,Zhu, Xiao Qin,Meng, Xiao
-
p. 3373 - 3377
(2013/01/15)
-
- Rare earth metal triflates catalyzed electrophilic nitration using N 2O5
-
A mild, efficient and eco-friendly process for the electrophilic nitration is described using N2O5 as a green nitrating agent in the presence of rare earth metal triflates [RE(OTf)3] under mild conditions.
- Ma, Xiao Ming,Li, Bin Dong,Lu, Ming,Lv, Chun Xu
-
experimental part
p. 73 - 76
(2012/03/26)
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- Selective nitration of aromatic compounds catalyzed by Hβ zeolite using N2O5
-
A selective and efficient process for the electrophilic nitration is described using N2O5 as a green nitrating agent, Hβ zeolite as a solid acid catalyst and shape controlling agent under mild conditions.
- Ma, Xiao Ming,Li, Bin Dong,Chen, Lei,Lu, Ming,Lv, Chun Xu
-
scheme or table
p. 809 - 812
(2012/08/08)
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- Aromatic nitration with bismuth nitrate in ionic liquids and in molecular solvents: A comparative study of Bi(NO3)3·5H 2O/[bmim][PF6] and Bi(NO3)3· 5H2O/1,2-DCE systems
-
A suspension of bismuth nitrate pentahydrate (BN) in [bmim][PF6] or [bmim][BF4] imidazolium ionic liquid (IL) is an effective reagent for ring nitration of activated aromatics under mild conditions without the need for external promoters. Nitration can also be effected in 1,2-DCE, MeCN, or MeNO2 without additives. Nitration of activated arenes (anisole, toluene, ethylbenzene, cumene, p-xylene, mesitylene, durene, and 1,3-dimethoxybenzene) is considerably faster (time to completion) in BN/[bmim][PF6] relative to BN/1,2-DCE and there are also differences in isomer distributions (for anisole, toluene, and ethylbenzene). With introduction of strongly deactivating substituents (-CHO; -MeCO; -NO 2) the BN/IL system is no longer active but reactions still proceed with BN/1,2-DCE in reasonable yields. The ready availability and low cost of BN, simple operation, and absence of promoters, coupled to recycling and reuse of the IL, provide an attractive alternative to classical nitration methods for activated arenes. Switching from Bi(NO3)3·5H 2O/[bmim][PF6] to Bi(NO3)3· 5H2O/1,2-DCE increases the scope of the substrates that can be nitrated.
- Jacoway, Jonathan,Kumar, G. G. K. S. Narayana,Laali, Kenneth K.
-
p. 6782 - 6785,4
(2012/12/12)
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- Ethylammonium nitrate (EAN)/Tf2O and EAN/TFAA: Ionic liquid based systems for aromatic nitration
-
Acting as in situ sources of triflyl nitrate (TfONO2) and trifluoroacetyl nitrate (CF3COONO2), the EAN/Tf 2O and EAN/TFAA systems, generated via metathesis in the readily available ethylammonium nitrate (EAN) ionic liquid as solvent, are powerful electrophilic nitrating reagents for a wide variety of aromatic and heteroaromatic compounds. Comparative nitration experiments indicate that EAN/Tf2O is superior to EAN/TFAA for nitration of strongly deactivated systems. Both systems exhibit low substrate selectivity (K T/KB = 5-10) in (Figure presented) between values reported for covalent nitrates and preformed nitronium salts.
- Aridoss, Gopalakrishnan,Laali, Kenneth K.
-
experimental part
p. 8088 - 8094
(2011/11/13)
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- An efficient and eco-friendly MoO3-SiO2 solid acid catalyst for electrophilic aromatic nitration with N2O5
-
Electrophilic aromatic nitration using N2O5 as a green nitrating agent catalyzed by MoO3-SiO2 under mild conditions has been described. A series of MoO3-SiO2 catalysts with varying MoO3 loadings (5-20 mol%) were prepared by sol-gel technique and characterized using FTIR, XRD, SEM, BET and NH 3-TPD to study its surface properties. MoO3-SiO 2 shows good catalytic activity and reusability for the nitration of alkyl and halogen aromatics giving high conversions, but less efficiency for the deactivated aromatics. Reactions conducted under non-acidic conditions using N2O5 makes the process safe and environmentally friendly. Graphical Abstract: [Figure not available: see fulltext.]
- Ma, Xiaoming,Li, Bindong,Lv, Chunxu,Lu, Ming,Wu, Jian,Liang, Linjie
-
experimental part
p. 1814 - 1820
(2012/03/08)
-
- Negishi coupling of secondary alkylzinc halides with aryl bromides and chlorides
-
(Chemical Equation Presented) An efficient palladium-catalyzed process has been developed for Negishi coupling of secondary alkylzinc halides with a wide range of aryl bromides and activated aryl chlorides. A palladium catalyst composed of a new biaryldialkylphosphine ligand, CPhos, effectively promotes the rate of the reductive elimination step relative to the rate of the undesired β-hydride elimination. The broad substrate scope and excellent ratio of the desired secondary to the undesired primary coupling product make this method a powerful and reliable tool forC(sp3)-C(sp2) bond formation.
- Han, Chong,Buchwald, Stephen L.
-
supporting information; experimental part
p. 7532 - 7533
(2009/10/16)
-
- Selective oxidation of aromatic amines to nitro derivatives using potassium iodide-tert-butyl hydroperoxide catalytic system
-
The direct oxidation of aromatic primary amines to the corresponding nitro compounds selectively in 47-98% yields has been achieved by using potassium iodide as catalyst and tert-butyl hydroperoxide as the external oxidant. The present catalytic system works well for both electron-rich and electron-poor substrates.
- Reddy, K. Rajender,Maheswari, C. Uma,Venkateshwar,Kantam, M. Lakshmi
-
supporting information; experimental part
p. 93 - 96
(2009/08/07)
-
- Synthesis of o-nitrosoacylbenzenes from o-nitrobenzyl alcohols and their derivatives
-
Nitration of substituted benzyl alcohols, as well as ethers and esters derived therefrom, with nitric acid in acetic anhydride was studied. The corresponding o-nitrobenzyl alcohols and their derivatives formed as the primary products are capable of being converted into o-nitrosoacylbenzenes by the action of acids. Pleiades Publishing, Inc., 2006.
- Gazzaeva,Fedotov,Trofimova,Popova,Mochalov,Zefirov
-
-
- Indium triflate as a recyclable catalyst for the nitration of aromatic compounds without a halogenated solvent
-
Indium triflate [In(OTf)3] was found to be excellent catalyst (0.5 or 2.0 mol%) for the mononitration of aromatic compounds using a single equivalent of nitric acid (60 or 90%, 1.0 equiv.) without using a halogenated solvent. The side product is water and the indium triflate catalyst can be readily recovered from the aqueous phase and reused.
- Yin, Wan-Po,Shi, Min
-
p. 549 - 551
(2007/10/03)
-
- Transformations of para-substituted benzylcyclopropanes, allylbenzenes, and diphenylmethanes under nitration with nitric acid in acetic anhydride
-
Electrophilic nitration of benzylcyclopropanes, allylbenzenes, and diphenylmethanes containing ortho, para-orienting substituents in the para position of the benzene ring results mainly in replacement of the cyclopropylmethyl, allyl, or benzyl group, respectively (ipso substitution). The nitration of 4-cyclopropylallylbenzene is not accompanied by nitrodealkylation, and the products are only 2- and 3-nitro-4-cyclopropylallylbenzenes.
- Mochalov,Gazzaeva,Fedotov,Archegov,Trofimova,Shabarov,Zefirov
-
p. 406 - 416
(2007/10/03)
-
- Electrophilic Aromatic Nitration Using a Mixed Catalyst of Lithium, Molybdenum, Ytterbium on Silica Gel
-
A novel mixed catalyst of LiClO4 (15% w/w), Yb(OPf)3 (15% w/w, Pf = perfluorooctanesulfonyl), MoO3 (15% w/w) on silica gel for electrophilic aromatic nitration reaction has been explored. The nitration reactions were accomplished by this mixed catalyst and nitric acid under solvent-free conditions. Moreover, the mixed catalyst can be easily recovered from the aqueous layer by heating in an oven and reused for the next nitration reaction.
- Shi, Min,Cui, Shi-Cong
-
p. 1329 - 1333
(2007/10/03)
-
- Alkylation of nitroarenes with Grignard reagents via oxidative nucleophilic substitution of hydrogen
-
Alkylation of nitroarenes with Grignard reagents via oxidative nucleophilic substitution of hydrogen (ONSH) can be efficiently executed with potasium permanganate in liquid ammonia as an oxidative system for the σH adducts. The addition of RMgX to ArNO2 of stoichiometry 1:1 is accompanied with a redox process apparently of stoichiometry 2:1. Because of that, real stoichiometry of the reaction between nitroarenes and Grignard reagents is ca. 1:1.5.
- Ma?kosza, Mieczys?aw,Surowiec, Marek
-
p. 167 - 171
(2007/10/03)
-
- Nitration of alkylbenzenes in acid medium: Regioselectivity of the reaction and acidity of the medium
-
Isomer distribution in the nitration of toluene and its homologs with nitric acid in acid media (trifluoroacetic acid and solutions of sulfuric acid in acetic acid) is determined by the acidity of the medium, the degree of para substitution changing in parallel with the acidity. The ortholpara regioselectivity is governed by the polarity of the transition state. The sensitivity of the ortholpara ratio to variation of the acidity of the medium and reaction temperature is directly related to steric effects of the alkyl groups.
- Krylov
-
p. 1413 - 1418
(2007/10/03)
-
- Selective nitration of aromatic compounds by solid acid catalysts
-
High activity and para-selectivity in the nitration of aromatic compounds is achieved by a high density of acidic sites and ready formation of the para-isomer in the pores of zeolite beta with low Si/Al ratio as revealed by molecular modeling studies.
- Choudary,Sateesh,Lakshmi Kantam,Koteswara Rao,Ram Prasad,Raghavan,Sarma
-
-
- Regioselectivity of the mononitration of alkylbenzenes by immobilized acyl nitrates
-
Mononitration of alkylbenzenes was studied using acyl nitrates and trimethylsilyl nitrate supported on clay-minerals. Chrysotile gave higher performance than other materials. High para-selectivity was obtained with the supported reagents. Nitration of tol
- Augusto,Rodrigues,Pedro Oliveira Filho,Moran, Paulo J. S.
-
p. 2169 - 2174
(2007/10/03)
-
- A novel method for the nitration of simple aromatic compounds
-
Simple aromatic compounds such as benzene, alkylbenzenes, halogenobenzenes, and some disubstituted benzenes are nitrated in excellent yields with high regioselectivity under mild conditions using zeolite β as a catalyst and a stoichiometric quantity of nitric acid and acetic anhydride. The zeolite can be recycled, and the only byproduct is acetic acid, which can be separated easily from the nitration product by distillation; the process is inexpensive and represents an attractive method for the clean synthesis of a range of nitroaromatic compounds. For example, nitration of toluene gives a quantitative yield of mononitrotoluenes, of which 79% is 4-nitrotoluene; fluorobenzene gives a quantitative yield of mononitro compounds, of which 94% is 4-nitrofluorobenzene; and 2-fluorotoluene gives a 96% yield of mononitro products, of which 90% is the 5-nitro isomer and 10% is the 4-nitro isomer.
- Smith, Keith,Musson, Adam,DeBoos, Gareth A.
-
p. 8448 - 8454
(2007/10/03)
-
- Synthesis of functionalized carbamates through a palladium-catalyzed reductive carbonylation of substituted nitrobenzenes
-
The palladium-catalyzed reductive carbonylation of ortho and para-substituted nitrobenzenes has proven to be an attractive route for the synthesis of functionalized carbamates. For the Pd(1,10-phenanthroline)2(triilate}2 catalyst system, the scope of the reaction has been studied. Substrates with electron-donating substituents at the para position were found to decrease the catalytic activity, most probably as a result of their relatively low oxidizing capacity. The selectivity towards the desired carbamate, however, was increased for these substrates. Under the influence of electron-withdrawing substituents the azoxybenzene and azobenzene derivatives became important side products. Introduction of large steric hindrance at the ortho position of the nitro substrates gave rise to an interesting side reaction, viz. methoxylation of the aromatic ring. The methoxylation reaction appeared to occur on an intermediate species in the catalytic cycle. Several functionalities have shown to be resistant to the reaction conditions required for the conversion of the nitro group. Especially with 4-nitrobenzoic acid, an extremely high activity and selectivity was found, thus yielding a very convenient synthesis for N-protected amines containing carboxylic acid functions. VCH Verlagsgesellschaft mbH.
- Wchman, Petra,Borst, Leo,Kamer, Paul C. J.,Van Leeuwen, Piet W. N. M.
-
-
- Nitration of Alkylbenzenes in Trifluoroacetic Acid
-
The substrate selectivity of alkylbenzene nitration with nitric acid in trifluoroacetic acid is controlled either by electronic or by steric effects of the substituents, depending the medium composition and temperature. The positional selectivity of this reaction is sterically controlled, even under electronic control of substrate selectivity.
- Krylov,Gvozdareva
-
p. 1618 - 1623
(2007/10/03)
-
- Substituent Effect in C-Isopropylation of Benzene Derivatives in the Nitrobenzene-Methanesulfonic Acid-Isopropyl Methanesulfonate System
-
Relative reactivities of chlorobenzene, o-dichlorobenzene, and nitrobenzene in C-isopropylation in the system nitrobenzene-methanesulfonic acid-isopropyl methanesulfonate at 298 K and the initial regioselectivity of the reaction were studied.Correlation analysis shows that sensitivity of the reaction to mesomeric effects of the substituents increses with decreasing activity of the substrate.
- Zaraiskaya, N. A.,Kachurin, O. I.
-
p. 641 - 644
(2007/10/03)
-
- Ozone-mediated Nitration of Alkylbenzenes and Related Compounds with Nitrogen Dioxide
-
In the presence of ozone, nitrogen dioxide exhibits a strong nitrating ability for alkylbenzenes at low temperatures, converting them into the corresponding nitro derivatives in high yield.The addition of a protonic acid as catalyst enhances considerably the ability of this nitrating system and leads to a good yield of polynitro compounds.The reaction is clean and proceeds rapidly without any accompanying side-chain substitution or aryl-aryl coupling.It shows no kinetic dependence on the concentration of substrates and, as far as can be judged from relative reactivities and isomer distributions of products, it gives the appearance of being an electrophilic aromatic process.A possible role for nitrogen trioxide has been suggested as the initial electrophilic agent for the nitration of alkylbenzenes.
- Suzuki, Hitomi,Murashima, Takashi,Kozai, Iku,Mori, Tadashi
-
p. 1591 - 1598
(2007/10/02)
-
- Reduction of Substituted Nitro Compounds with Tri-n-butyltin Hydride
-
α-Substituted nitro compounds have been reduced with tri-n-butyltin hydride to give replacement of the α-substituent by hydrogen (2-bromo, 2-chloro- and 2-nitro-2-phenylsulphonylpropane to 2-nitropropane; p-nitrobenzyl chloride, bromide, iodide and thiocyanate to p-nitrotoluene; 5-nitrofurfuryl nitrate to 2-methyl-5-nitrofuran and 2-hydroxymethyl-5-nitrofuran; 2-(bromomethyl)-1-methyl-5-nitroimidazole to 1,2-dimethylimidazole). 2-Bromo-2-nitrohept-6-ene and 1-bromo-1-nitrohex-5-ene were reduced to 2-nitrohept-6-ene and 1-nitrohex-5-ene,5-bromo- and 5-phenylsulphonyl-5-nitro-6-phenyl-norborn-6-ene to 5-nitro-6-phenylnorborn-6-ene and 2-iodo-2-nitro-3-(endo-norborn-2-en-5-yl)propane to 2-nitro-3-(endo-norborn-2-en-5-yl)propane without cyclisation of the intermediate alkenyl α-nitroalkyl radicals. 2-Bromo-2-nitrohex-5-ene and 1-bromo-1-nitropent-4-ene were reduced to the respective nitroalkenes at high but at lower cyclisation to 1-methyl-1-nitrocyclopentane and 1-nitrocyclopentane took place.Inhibition studies of the reductions of 2-bromo-2-nitrohex-5-ene and p-nitrobenzyl bromide showed a radical chain mechanism.In some of the reductions at low , radical rearrangement of the intermediate α-nitroalkyl radicals gave the respective ketones.Mechanisms involving (a) addition/elimination and (b) dissociation of intermediate radical anions, are proposed.
- Bowman, W. Russell,Crosby, David,Westlake, Paul J.
-
-
- PARA-SELECTIVE MONONITRATION OF ALKYLBENZENES UNDER MILD CONDITIONS BY USE OF BENZOYL NITRATE IN THE PRESENCE OF A ZEOLITE CATALYST
-
Toluene and other alkylbenzenes are mononitrated in essentially quantitative yield at ambient temperature by benzoyl nitrate in the presence of aluminium/proton exchanged large port mordenite; the reaction is highly para-selective.
- Smith, Keith,Fry, Karl,Butters, Michael,Nay, Barry
-
p. 5333 - 5336
(2007/10/02)
-
- THE SELECTIVITY OF ELECTROPHILIC AROMATIC NITRATION AND THE EFFECT OF THE ORGANIC SOLVENTS
-
The nitrating agent prepared by mixing Bu4NNO3 and (CF3CO)2O has been used to nitrate in homogeneous conditions eight aromatic substrates, ranging in reactivity from benzene to mesitylene, in several organic solvents.From competitive kinetic experiments and glc analysis, partial rate factors were obtained.The nature of the solvent significantly affects selectivity in the whole activation range.Selectivity was quantitatively measured by the selectivity factor for toluene, and, more properly, by the slopes in the correlations between log values of partial rate factors in a given solvent and the corresponding values in a reference solvent.Good correlations were obtained also including ortho positions and polysubstituted substrates, and the following order of relative selectivity could be established: MeNO2 MeCN /= sulfolane CH2ClCH2Cl CH2Cl2 /= EtOAc /= i-PrBr = n-BuCl = n-BuBr /= CHCl3.Correlation between partial rate factors has been extended to compare the selectivity of different nitrating agents in the same solvent, and the method can be used to ascertain whether the same electrophilic species actually operates in the two systems.
- Masci, Bernardo
-
p. 2719 - 2730
(2007/10/02)
-
- REGIOSELECTIVE NITRATION OF AROMATIC HYDROCARBONS BY METALLIC NITRATES ON THE K10 MONTMORILLONITE UNDER MENKE CONDITIONS
-
Aromatic hydrocarbons are nitrated with good regioselectivities by clay-supported cupric nitrate in the presence of acetic anhydride.The procedure commends itself by its simplicity and gives useful yields (75-98percent).In each case, the predominant product can be predicted by consideration of the Hueckel HOMO for the aromatic ring.
- Laszlo, Pierre,Vandormael, Joseph
-
p. 1843 - 1846
(2007/10/02)
-
- Electrophilic Aromatic Nitration in the Gas Phase
-
Aromatic nitration by MeO+(H)NO2, in essence nitronium ion solvated by one methanol molecule, has been studied in the gas phase by using an integrated approach, based on the coordinate application of ICR, Cl, and CID mass spetrometric methods with a highly complementary radiolytic technique.The latter can be used in gases at atmospheric pressure and allows direct evaluation of key mechanistic features, in particular of substrate and positional selectivity.The results resolve early discrepancies between gas-phase and liquid-phase studies, characterizing the reaction as a typical, well-behaved electrophilic substitution of moderate selectivity.The date from the gas-phase nitration of ten monosubstituted benzenes fit a Hammett's type linear plot, characterized by a ρ value of -3.87.The correlation does not extend to highly activated substrates, such as anisole and mesitylene, since the nitration rate tends to a limiting value that cannot be increased by further enhancing the activation of the substrate, exactly as in "encounter-rate" nitrations occurring in solution.The mechanism and the energetics of the gas-phase nitration have been investigated, and the relative stability of the charged intermediates involved, in particular of the isomeric protonated nitrobenzenes, has been estimated by theoretical approaches at two different levels, using STO-3G minimal basis and 4-31G split-valence basis sets.
- Attina, Marina,Cacace, Fulvio,Yanez, Manuel
-
p. 5092 - 5097
(2007/10/02)
-
- REACTIVITY OF HETEROCYCLIC AMBIENT S...N ANIONS IN SRN1 SUBSTITUTION REACTIONS
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Ambident anions of 2-mercaptoazoles react, under photo- stimulation conditions, with α,p-dinitrocumene according to an SRN1 mechanism (short chain) leading to S-alkylated compounds in agreement with a kinetically controlled reaction.Regioselect
- Meyer, Monique,Samat, Andre,Chanon, Michel
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p. 1013 - 1018
(2007/10/02)
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- Some Studies on the Reversibility of the Association Step in SRN1 Reactions
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The association step in SRN1 reactions, in which p-nitrobenzylic radicals are trapped by aci-nitronate ions or the anions from β-keto esters, is demonstrated to be effectively irreversible under the normal conditions of the SRN1 reac
- Norris, Robert K.,Wright, Timothy A.
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p. 1107 - 1116
(2007/10/02)
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- NITRATION OF ALKYLBENZENES WITH NITRIC ACID IN ORGANIC SOLVENTS. SUBSTRATE AND POSITION SELECTIVITY
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The substrate and position selectivity in the nitration of alkylbenzenes (with normal and iso C1-C4 alkyl groups) in organic solvents (protic and bipolar aprotic solvets) with and without sulfuric acid in the range of 25-75 deg C is determined mainly by the steric affect of the substituents.Nathan-Bacer substrate and position effects are observed.Linear correlations are found between the result of the orientation of the nitro group and the steric parameters of the substituets.The substrate selectivity varies inversely and the position selectivity varies directly with the latter.The sensitivity of the orientation to change in the geometry of the substituets varies directly with temperature.
- Krylov, E. N.,Khromova, I. N.
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p. 2179 - 2186
(2007/10/02)
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- Reactions of Cerium(IV) Ammonium Nitrate with Aromatic Compounds in Acetonitrile. Part 2. Nitration; Comparison with Reactions of Nitric acid
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The nitration of benzene and a number of alkylbenzenes by cerium(IV) ammonium nitrate in acetonitrile shows the same intra- and inter-molecular selectivity as nitration with nitric acid under the same conditions but the extent of the other products formed in the two sets of reactions is very different.Nitration by cerium(IV) ammonium nitrate (but not side-chain substitution) is suppressed by the addition of water.The results suggest that these nitration reactions by cerium(IV) ammonium nitrate occur through the intermediate formation of a nitronium ion from the cerium(IV) complex but the order with recpect to the aromatic compound shows that this nitronium ion must then be formed in the presence of the aromatic substrate as a 'spectator'.The relative reactivities with respect to benzene in the nitration of anisole and naphthalene are much greater than those observed in nitration by nitric acid and, with both, the isomer proportions are also anomalous.
- Dinctuerk, Suphi,Ridd, John H.
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p. 965 - 970
(2007/10/02)
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- Aromatic Substitution. 48. Boron Trifluoride Catalyzed Nitration of Aromatics with Silver Nitrate in Acetonitrile Solution
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Benzene, alkylbenzenes, halobenzenes, and anisole were nitrated with silver nitrate/boron trifluoride in acetonitrile solution.Correlation of competitive rates with ?- and ?-complex stabilities indicated that the transition state of highest energy lies relatively early on the reaction coordinate.Data indicate that nitrations occur via a polarized complex of the nitrating agent, with the catalyst undergoing nucleophilic displacement by the aromatic substrate.
- Olah, George A.,Fung, Alexander P.,Narang, Subhash C.,Olah, Judith A.
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p. 3533 - 3537
(2007/10/02)
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- Aromatic Substitution. 471. Acid-Catalyzed Transfer Nitration of Aromatics with N-Nitropyrazole, a Convenient New Nitrating Agent
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N-Nitropyrazole in the presence of Lewis or Bronsted acid catalysts was found to be an effective transfer nitrating agent for aromatic substrates.The nature of the acid catalyst both substrate and positional selectivies of the nitration of alkylbenzenes.No relationship was found between substrate and positional selectivities, which are considered to be determined in two separate steps.
- Olah, George A.,Narang, Subhash C.,Fung, Alexander P.
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p. 2706 - 2709
(2007/10/02)
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- Electrophilic aromatic substitution. Part 24. The nitration of isopropylbenzene, 2- and 4-isopropyltoluene, 1-chloro-4-isopropylbenzene, 4-isopropylanisole, and 2-bromotoluene: Nitrodeisopropylation
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The kinetics and products of nitration in aqueous sulphuric acid of the title compounds have been studied. 4-Isopropyl-phenol and -anisole are nitrated at or near the encounter rate. In 65-79% H2SO4 2-isopropyltoluene suffers ca. 25% ipso-attack; the only fate of W iPri (ipso-Wheland intermediate) is nitrodeisopropylation. From 4-isopropyltoluene WiPri is also nitrodeisopropylated, but some 1,2-nitro-migration may occur. From the same compound WiMe may be captured by water, rearrange, or give 4-methylacetophenone; a mechanism is proposed for the formation of the last compound. Nitrodeisopropylation occurs without the assistance of water. With 4-isopropylanisole, demethoxylation and nitrodeisopropylation are consequences of the formation of WiPri. The results are consistent with increasing attack at C-4 with increasing acidity, loss of isopropyl without assistance from water, and decomposition of the unobserved intermediate, 4-isopropyl-4-nitrocyclohexa-2,5-dienone, by two processes. One, acid-catalysed process gives 4-nitrophenol and possibly 4-isopropyl-2-nitrophenol. The other, probably radical, process gives 4-isopropyl-2-nitrophenol. In contrast to 4-bromotoluene, 2-bromotoluene is not nitrodebrominated.
- Manglik, Ajay K.,Moodie, Roy B.,Schofield, Kenneth,Tobin, Geoffrey D.,Coombes, Robert G.,Hadjigeorgiou, Panicos
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p. 1606 - 1616
(2007/10/02)
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- Electron-Transfer Chain-Substitution Reactions of Ambident Anions
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A simple explanation is proposed for the fact that electron-transfer chain-substitution reactions involving ambident anions give only one of the two possible products and experimental evidence which supports this hypothesis is presented.
- Kornblum, Nathan,Ackermann, Peter,Swiger, R. T.
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p. 5294 - 5298
(2007/10/02)
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