880-93-3

Usage

Uses

Used in Pharmaceutical Industry:
1-METHYL-4-NITRONAPHTHALENE is used as a key intermediate in the synthesis of S-triazolyl α-mercaptoacetanilides, which are inhibitors of HIV reverse transcriptase. These compounds play a crucial role in the development of antiretroviral drugs, as they help in the treatment and management of HIV/AIDS by inhibiting the replication of the virus.
In the preparation of S-triazolyl α-mercaptoacetanilides, 1-METHYL-4-NITRONAPHTHALENE serves as a starting material, which undergoes a series of chemical reactions to form the desired active pharmaceutical ingredients. The synthesis process typically involves the formation of a triazole ring, followed by the introduction of a mercaptoacetanilide moiety. The resulting compounds exhibit potent inhibitory activity against HIV reverse transcriptase, making them valuable candidates for further research and development in the field of antiretroviral therapy.

InChI:InChI=1/C11H9NO2/c1-8-6-7-11(12(13)14)10-5-3-2-4-9(8)10/h2-7H,1H3

Upstream product

• 624-91-9 methyl nitrite 
• 90-12-0 1-Methylnaphthalene 
• 625-58-1 ethyl nitrate 
• 7446-70-0 aluminium trichloride 
• 7697-37-2 nitric acid 
• 64-19-7 acetic acid 
• 108-24-7 acetic anhydride 
• 103986-53-4 4-methyl-1-naphthylboronic acid 

Downstream Products

• 1975-43-5 4-nitro-1-naphthoic acid 
• 4523-45-9 1-amino-4-methylnaphthalene 
• 61757-43-5 4-amino-1-naphthaldehyde 
• 16855-41-7 1-(bromomethyl)-4-nitronaphthalene 
• 108450-99-3 4-Methyl-1-nitro-2-(p-tolylsulfonylmethyl)naphthalene 
• 20601-22-3 2-bromo-1-methylnaphthalene 
• 51670-78-1 1-acetamido-4-methylnaphthalene 
• 81503-62-0 2,4,6-trimethylbenzo[h]quinolone 
• 4523-52-8 1-dimethylamino-4-methylnaphthalene 

Relevant academic research and scientific papers

1,4-SUBSTITUTED ISOQUINOLINE INHIBITORS OF KEAP1/NRF2 PROTEIN-PROTEIN INTERACTION

Disclosed herein are compounds that can act as inhibitors of the Kelch-like ECH- associated protein 1/nuclear factor (erythroid-derived 2)-like 2 ("KEAP1/NRF2") protein- protein interaction, and methods of using the compounds to treat and prevent diseases and disorders, such as COPD, multiple sclerosis, and diabetes, and in the promotion of wound healing. The compounds described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: formula (I), wherein the substituents are as described.

A Facile Synthesis of Benzo[h]quinolines via Silica-TsOH-P2O5 Promoted Condensation of 1-Naphthylamines with 1,3-Diketones under Solvent Free Conditions

A facile synthesis of benzo[h]quinolines has been developed via improved Combes reaction. A combination of silica gel, p-toluenesulfonic acid and phosphorus pentoxide was utilized to promote the condensation of 1-naphthylamines with 1,3-diketones under solvent free conditions. In this case, silica gel was used as reaction media, p-toluenesulfonic acid and phosphorus pentoxide were acted as catalyst and dehydrating agent, respectively.

Green and controllable metal-free nitrification and nitration of arylboronic acids

A novel and green nitrating reagent has been developed for the nitrification and nitration of arylboronic acids, which can be controlled by the reaction conditions. The process provides an attractive alternative to the traditional nitration protocols.

Copper-catalyzed nitration of arylboronic acids with nitrite salts under mild conditions: An efficient synthesis of nitroaromatics

Copper-catalyzed nitration of arylboronic acids has been developed with nitrite salts as nitrating agent under mild conditions. This process provides an efficient and practical method for the synthesis of nitro aromatics, due to its simple experimental procedure and its use of convenient and inexpensive copper catalyst.

Aromatic nitration in liquid Ag0.51K0.42Na 0.07NO3

(Figure Presented) Aromatic molecules have a strong affinity for silver(I) and dissolve to a limited extent in Ag0.51K0.42Na 0.07NO3, a low-melting eutectic mixture of silver, potassium, and sodium nitrates. Aromatic nitration in this inorganic ionic liquid leads to products which arise from nonelectrophilic substitution pathways.

S-TRIAZOLYL α-MERCAPTOACETANILDES AS INHIBITORS OF HIV REVERSE TRANSCRIPTASE

A series of S-triazolyl α-mercaptoacetanilides having general structure (1) are provided, where Q is CO2H, CONR2, SO3H, or SO2NR2. The compounds inhibit several variants of the reverse transcriptase of HIV, and are useful in the treatment of HIV infections.

Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1h-indol-4ylmethylene]hydrazide

Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-cyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure - metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, KB = 760 pM) and of the isolated rat receptor (IC50 = 430 pM, KB = 380 pM). Glucagonstimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (Ki = 14 nM). This compound was orally available in dogs (Fpo = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.

NO2+ nitration mechanism of aromatic compounds: Electrophilic vs charge-transfer process

The nitration of methylnaphthalenes with NO2BF4 and NOBF4 was examined in order to shed light on the controversial aromatic nitration mechanism, electrophilic vs charge-transfer process. The NO2+ nitration of 1,8-dimethylnaphthalene showed a drastic regioselectivity change depending on the reaction temperature, where ortho-regioselectivity at -78 °C and para- regioselectivity at 0 °C were considered to reflect the electrophilic and the direct or alternative charge-transfer process, respectively, because the NO+ nitration through the same reaction intermediates as in the NO2+ nitration via a charge-transfer process resulted in para-regioselectivity regardless of the reaction temperature. The NO2+ nitration of redox potential methylnaphthalenes higher than 1,8-dimethylnaphthalene gave a similar ortho-regioselectivity enhancement to 1,8-dimethylnaphthalene at lower temperature, thus reflecting the electrophilic process. On the other hand, the NO2+ nitration of redox potential methylnaphthalenes lower than 1,8-dimethylnaphthalene showed para-regioselectivity similar to the NO+ nitration, indicating the direct or alternative charge-transfer process. In the presence of strong acids where the direct charge-transfer process will be suppressed by protonation, the ortho-regioselectivity enhancement was observed in the NO2+ nitration of 1,8-dimethylnaphthalene, suggesting that the direct charge-transfer process could be the main process to show para- regioselectivity. These experimental results imply that the NO2+ nitration proceeds via not only electrophilic but also direct charge-transfer processes, which has been considered to be unlikely because of the high energy demanding process of a bond coordination change between NO2+ and NO2. Theoretical studies at the MP2/6-31G(d) level predicted ortho- and para-regioselectivity for the NO2+ nitration via electrophilic and charge- transfer processes, respectively, and the preference of the direct charge- transfer process over the alternative one, which support the experimental conclusion.

Internal conversion in 4-substituted 1-naphthylamines. Influence of the electron donor/acceptor substituent character

The thermally activated internal conversion (IC) taking place in 4- substituted 1-(dimethylamino)naphthalenes (14DMX) and 1-aminonaphthalenes (14ANX) with X = CN, Cl, H, CH3 and OCH3 was investigated in three solvents spanning the polarity scale, hexane, diethyl ether and acetonitrile. In both series 14DMX and 14ANX, the efficiency of the IC reaction decreases substantially when X changes from CN to OCH3, the order in which the electron donor character of the 4-substituent increases. Considerably larger IC reaction rate constants are obtained for the first group of compounds. This difference is connected with the ground state structure of the amino group, which is more strongly twisted for 14DMX (ca. 60°) than for 14ANX (ca. 20°), whereas both sets of 1-naphthylamines are planarised in the S1 excited state. The IC process slows down with increasing solvent polarity for each of the 14DMX and 14ANX molecules. The substituent X and the solvent polarity mainly affect the IC activation energy E(IC). With 14DMX in hexane, E(IC) increases from 10 kJ mol-1 for X = CN to 34 kJ mol-1 for X = OCH3, whereas with, e.g., 14DMCL a solvent polarity dependent increase of E(IC) from 16 kJ mol-1 in hexane to 28 kJ mol-1 in acetonitrile is observed. The height of the barrier E(IC) is governed by the energy gap ΔE(S1,S2) between the two lowest excited singlet states. The influence of δE(S1,S2) on E(IC) is attributed to vibronic coupling caused by the proximity of the S1 and S2 states, which flattens the S1 potential energy surface and thereby lowers the IC barrier when ΔE(S1,S2) becomes smaller. It is assumed that the IC reaction of the 1-naphthylamines passes through a conical intersection, which exists as a consequence of the relative displacement of the S1 and S0 surfaces caused by the different amino twist angles in the two states.

Iron(III)-catalysed nitration of non-activated and moderately activated arenes with nitrogen dioxide-molecular oxygen under neutral conditions

In the presence of molecular oxygen and a catalytic amount of tris(pentane-2,4-dionato)iron(III), non-activated and moderately activated arenes, which include alkylbenzenes, halogenobenzenes, phenolic ethers, naphthalene and derivatives, can be nitrated with nitrogen dioxide at ice-bath temperature or below to give the corresponding nitro derivatives in fair to good yields. An electron-transfer mechanism has been proposed, where an activated NO2-FeIII complex plays a key role in the cyclic process for converting arenes into nitroarenes.