Nitro Source Research Articles

Selective C6‐Nitration of Benzothiazolones with Iron Nitrate

AbstractWe report here a selective C6‐nitration of benzothiazolones in the presence of iron nitrate as nitro source. A series of novel 6‐nitrobenzothiazolin‐2‐one derivatives were prepared with moderate to excellent yields at room temperature. The method shows good regioselectivity, broad substrate scope and excellent compatibility with functional groups. Further transformations were performed for the reduction of nitro groups, amination of carbonyl groups and alkylation of amine at the 3‐position in the product.

Nitration of Benzene to Nitrobenzene Using NO2 as Nitro Source Under Mild and Solvent‐Free Conditions

AbstractIn this work, a green and efficient method has been developed to catalyze the nitration of benzene to nitrobenzene in NO2‐O2 system by using acidic ion exchange resin as catalyst under mild (0 °C and atmospheric pressure) and solvent‐free conditions. Based on experimental screening, commercial acid ion exchange resin Amberlite FPC3500 was identified as the optimal catalyst. Under the optimized reaction conditions, 99.9 % conversion of benzene was obtained with 99.1 % selectivity of nitrobenzene. Furthermore, the catalyst is easily reusable. The results demonstrate a greener route for the production of nitrobenzene.

Regioselective C(sp2)-H nitrosation and nitration of (Hetero)arenes with Fe(NO3)3·9H2O as promoter, nitroso and nitro source

A regioselective C(sp2)-H nitrosation and nitration protocol has been successfully developed for the modification of various undirected bioactive molecules by using the economical and nontoxic Fe(NO3)3.9H2O as nitroso/nitro source. This method is conducted under acid-free and ease of handling conditions and is featured with good regioselectivity as well as a broad substrate scope (38 examples; yields up to 90 %). This reaction could be conducted on a gram scale with good efficiency, demonstrating high utility for the synthesis and modification of drug and material molecules. Detailed mechanistic studies indicate that the formation of the nitroso or nitro products might be proceeded via the radical cross coupling of aryl radical cation intermediates with nitroso or nitro radical.

Nitration of Derivatives of Imidazo[1,5‐a]pyridine via C−H Functionalization with Fe(NO3)3 ⋅ 9H2O as a Promoter and a Nitro Source

AbstractAn additive‐free, mild, and regioselective C(1)−H nitration of imidazo[1,5‐a]pyridine derivatives was developed. This protocol features the use of easily handled, commercially available, and nontoxic Fe(NO3)3 ⋅ 9H2O both as a nitration source and as a promoter, exhibits good functional group compatibility, and generates the desired nitrated products in acceptable to excellent yields. Mechanistic studies proposed that the nitration reaction may involve a radical C−H functionalization process.

Visible-Light-Photocatalyzed C5-H Nitration of 8-Aminoquinoline Amides

A mild and efficient protocol for visible-light-photocatalyzed C5 nitration of 8-aminoquinoline derivatives was developed utilizing Cu(NO3)2∙3H2O as a nitro source. The reaction proceeded smoothly under very mild conditions, employing Acid Red 94 and a commercial household light bulb as an organic photosensitizer and a light source, respectively, making this synthetic procedure green and easy to operate. Furthermore, most products could be obtained through recrystallization, which enhanced the operational simplicity of this method.

Late-Stage C-H Nitration of Unactivated Arenes by Fe(NO3)3·9H2O in Hexafluoroisopropanol.

Operationally simple and generally applicable arene nitration with cheap and easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized this goal with nontoxic and inexpensive Fe(NO3)3·9H2O as the nitro source and easily recyclable solvent hexafluoroisopropanol as the promotor via a network of hydrogen-bonding interactions. As a result of the relative mildness and high reliability of this protocol, late-stage nitration of various highly functionalized natural products and commercially available drugs was realized.

Nitration of Pyrrolo[2,1‐a]isoquinolines with NaNO2/HFIP

AbstractA mild nitration of pyrrolo[2,1‐a]isoquinolines has been reached using sodium nitrite as nitro source in HFIP at ambient temperature. A variety of nitro‐bearing pyrrolo[2,1‐a]isoquinoline derivatives has been efficiently prepared in poor to quantitative yields (28–98 %). These products can be easily transformed to primary amines and amide by simple chemical reactions. Treatment of other nitrogen‐containing heterocycles such as pyrrolo[1,2‐a]quinoline and substituted indoles under this developed reaction system afforded nitro‐bearing N‐heterocycles in relatively lower yields (15–19 %).

Photochemical Nitration of Protected Anilines by 5‐Methyl‐1,4‐dinitroimidazole

Comprehensive SummaryNitroanilines are important building blocks in pharmaceuticals, materials and dyes. Nitration methods for anilines under mild conditions are highly desired. Herein, we report a photochemical method for the nitration of anilines bearing various protecting groups by 5‐methyl‐1,4‐dinitroimidazole as a new type of nitro source. This method is light‐controlled and proceeds under mild reaction conditions with high efficiency. Fmoc‐, Ts‐ and alkyl‐protected anilines are all well nitrated with good functional group tolerance.

Oxidative Cyclization of Aryl Ynones with NaNO2 for the Divergent Synthesis of NO2‐Containing Spiro[5.5]trienones, Indenones and Thioflavones

AbstractA K2S2O8‐promoted nitration/spirocyclization of biaryl ynones using inexpensive NaNO2 as nitro source has been described. This cascade reaction is triggered by nitration of alkyne and followed by 6‐exo‐trig spirocyclization, dearomatization, forming the NO2‐containing spiro[5.5]trienones in 63–85% yields. The present reaction also provides a practical method for the synthesis of nitrated indenones and thioflavones with 58–85% yields.magnified image

Nitration of N-acetyl anilides using silver(I) nitrate/persulfate combination

Nitration of N-acetyl anilides using a simple combination of AgNO3 and K2S2O8 as a stable nitro source and an oxidant, respectively, was explored. The reaction was practical to operate and proceeded under considerably mild reaction conditions (reflux in acetonitrile) within acceptable reaction time (6 h). The para-substituted N-acetyl anilides gave only ortho-nitrated products in moderate to good yields (30–63% yields). The ortho-, meta-, or non-substituted N-acetyl anilides gave a mixture of nitrated products (30–72% combined yields) with preferentially at the para- over the ortho-position (ortho:para; 1.0:1.1–1.0:2.8).

Electrochemical Nitration with Nitrite.

Aromatic nitration has tremendous importance in organic chemistry as nitroaromatic compounds serve as versatile building blocks. This study represents the electrochemical aromatic nitration with NBu4NO2, which serves a dual role as supporting electrolyte and as a safe, readily available, and easy‐to‐handle nitro source. Stoichiometric amounts of 1,1,1‐3,3,3‐hexafluoroisopropan‐2‐ol (HFIP) in MeCN significantly increase the yield by solvent control. The reaction mechanism is based on electrochemical oxidation of nitrite to NO2, which initiates the nitration reaction in a divided electrolysis cell with inexpensive graphite electrodes. Overall, the reaction is demonstrated for 20 examples with yields of up to 88 %. Scalability is demonstrated by a 13‐fold scale‐up.

Modified mesoporous Y zeolite catalyzed nitration of azobenzene using NO2 as the nitro source combined with density functional theory studies

A modified mesoporous Y zeolite (Fe–Y) is developed for high ortho regioselective nitration of azobenzene under a NO2–O2 system.

Synthesis of 2-Arylbenzothiazole and 2-Arylthiazole Derivatives via a Ru-Catalyzed meta-Selective C-H Nitration Reaction.

A Ru-catalyzed meta-selective C-H nitration of 2-arylbenzothiazoles and 2-arylthiazoles has been developed. A wide range of functional groups are tolerated, providing the meta-nitrated products in good to excellent yields using Cu(NO3)2·3H2O as the nitro source. The nitration could be carried out on a gram scale and used for the synthesis of promising therapeutic leads for human African trypanosomiasis.

Copper‐catalyzed C‐H Bis‐nitration of 1‐Naphthylamide Derivatives with tert‐Butyl Nitrite as Nitro Source

AbstractA simple and atom‐economical protocol for bis‐nitration of 1‐naphthylamides was firstly discovered with tert‐butyl nitrite (TBN) as nitro source and catalyzed by Cu(OAc)2. Assisted by picolinamide direction, the C2,4‐H bis‐nitration could be achieved with excess amount of TBN at 50°C in HOAc. A radical pathway and single electron transfer process might be involved in the bis‐nitration process.

Copper Nitrate‐Mediated Selective Difunctionalization of Alkenes: A Rapid Access to β‐Bromonitrates

AbstractA regioselective copper nitrate‐mediated difunctionalization of alkenes has been developed for the rapid synthesis of β‐bromonitrates, where copper nitrate is used as an ideal nitrooxy source for the first time and the products will find many applications in organic synthesis as versatile synthons. Different from the general reports that copper nitrate acts as the nitro source, the given protocol provides a direct access to functionalized nitrates, with operational simplicity, good functional group tolerance and a wide substrate scope.magnified image

Copper-Catalyzed Direct α-Nitration of Nitrostilbenes with Nitrogen Dioxide

A novel and efficient method for the direct α-nitration of nitrostilbenes was developed in which NO2 was used as the nitro source. This method provided (E)-α-nitrostilbenes derivatives in moderate to good yields. A broad substrate scope, mild and convenient conditions, and high stereoselectivity are important features of this method.

Nitration and Cyclization of Arene-Alkynes: An Access to 9-Nitrophenathrenes.

A nitration and cyclization of arene-alkynes has been developed, affording 9-nitrophenathrenes efficiently. This reaction probably proceeds via addition of the nitrogen dioxide to the alkyne moiety, intramolecular radical addition of vinyl radical to one aryl ring, oxidation of radical intermediate into carbocation species, and elimination of a proton. In this transformation, Fe(NO3)3 was used as both nitro source and oxidant.

Visible-Light-Induced Radical Polynitration of Arylboronic Acids: Synthesis of Polynitrophenols

We report a visible light-assisted one-pot method for the synthesis of polynitrophenols through radical tandem hydroxylation and nitration of arylboronic acids by utilizing copper(II) nitrate tri­hydrate as the nitro source. This method features mild conditions, a simple procedure, and good functional group tolerance. Compared to conventional methods, this work provides a straightforward approach for the polynitration of aromatic compounds.

Cobalt-Catalyzed C-H Nitration of Indoles by Employing a Removable Directing Group.

A mild and efficient C(sp2 )-H nitration of 3-substituted indoles, by using the economical and non-toxic cobalt nitrate hexahydrate [Co(NO3 )2 ⋅6 H2 O] as a catalyst and tert-butyl nitrite (TBN) as the nitro source, is reported. This approach provides a unique methodology involving a site-selective C-N bond formation for preparation of C-2 substituted nitro indoles. Utilization of the tBoc as the removable directing group enhances the synthetic utility of the method.

Regioselective nitration of anilines with Fe(NO3)3·9H2O as a promoter and a nitro source.

An efficient Fe(NO3)3·9H2O promoted ortho-nitration reaction of aniline derivatives has been developed. This reaction may go through a nitrogen dioxide radical (NO2˙) intermediate, which is generated by the thermal decomposition of iron(iii) nitrate. The practicality of the present method using nontoxic and inexpensive iron reagents has been shown by the broad substrate scope and applications.