188731-34-2

Upstream product

• 673-41-6 p-chlorobenzenediazonium tetrafluoroborate 
• 371-40-4 4-fluoroaniline 
• 106-47-8 4-chloro-aniline 
• 1073-69-4 N-4-chlorophenylhydrazine 
• 62-53-3 aniline 
• 1073-70-7 4-chlorophenylhydrazine hydrochloride 
• 2028-74-2 p-chlorobenzenediazonium chloride 
• 110213-25-7 C₆H₄ClN₂O^(1-)*Na⁽¹⁺⁾ 
• 71-43-2 benzene 

Relevant academic research and scientific papers

Regiospecific Introduction of Halogens on the 2-Aminobiphenyl Subunit Leading to Highly Potent and Selective M3 Muscarinic Acetylcholine Receptor Antagonists and Weak Inverse Agonists

Muscarinic M3 receptor antagonists and inverse agonists displaying high affinity and subtype selectivity over the antitarget M2 are valuable pharmacological tools and may enable improved treatment of chronic obstructive pulmonary disease (COPD), asthma, or urinary incontinence. On the basis of known M3 antagonists comprising a piperidine or quinuclidine unit attached to a biphenyl carbamate, 5-fluoro substitution was responsible for M3 subtype selectivity over M2, while 3′-chloro substitution substantially increased affinity through a σ-hole interaction. Resultantly, two piperidinyl-and two quinuclidinium-substituted biphenyl carbamates OFH243 (13n), OFH244 (13m), OFH3911 (14n), and OFH3912 (14m) were discovered, which display two-digit picomolar affinities with Ki values from 0.069 to 0.084 nM, as well as high selectivity over the M2 subtype (46-to 68-fold). While weak inverse agonistic properties were determined for the biphenyl carbamates 13m and 13n, neutral antagonism was observed for 14m and 14n and tiotropium under identical assay conditions.

Regiospecific Introduction of Halogens on the 2-Aminobiphenyl Subunit Leading to Highly Potent and Selective M3 Muscarinic Acetylcholine Receptor Antagonists and Weak Inverse Agonists

Muscarinic M3 receptor antagonists and inverse agonists displaying high affinity and subtype selectivity over the antitarget M2 are valuable pharmacological tools and may enable improved treatment of chronic obstructive pulmonary disease (COPD), asthma, or urinary incontinence. On the basis of known M3 antagonists comprising a piperidine or quinuclidine unit attached to a biphenyl carbamate, 5-fluoro substitution was responsible for M3 subtype selectivity over M2, while 3′-chloro substitution substantially increased affinity through a σ-hole interaction. Resultantly, two piperidinyl- A nd two quinuclidinium-substituted biphenyl carbamates OFH243 (13n), OFH244 (13m), OFH3911 (14n), and OFH3912 (14m) were discovered, which display two-digit picomolar affinities with Ki values from 0.069 to 0.084 nM, as well as high selectivity over the M2 subtype (46-to 68-fold). While weak inverse agonistic properties were determined for the biphenyl carbamates 13m and 13n, neutral antagonism was observed for 14m and 14n and tiotropium under identical assay conditions.

The use of the arylhydrazine synthetic amino of the biphenyl method

The present invention describes a method for synthesising 2-aminobiphenyls and derivatives thereof. This method can be performed cost-effectively and is based on selective reactions. Functionalised biphenyl compounds are of great interest, particularly as pharmaceuticals and agricultural chemicals, and as precursors for such active ingredients. The method for producing a compound of formula 3 is characterised in that a compound of formula 1 is reacted with a compound of formula 2 in the presence of an oxidising agent.

Radical Arylation of Anilines and Pyrroles via Aryldiazotates

The radical arylation of anilines and pyrroles can be achieved under transition-metal- and catalyst-free conditions by using aryldiazotates in strongly alkaline aqueous solutions. The aryldiazotates act as protected diazonium ions, which do not undergo azo coupling with electron-rich aromatic substrates, but can still serve as an aryl radical source at slightly elevated temperatures. Based on an improved preparation of aryldiazotates in aqueous solution, homolytic aromatic substitutions of anilines and pyrroles were conducted with good overall yields and high regioselectivity. Moreover, DFT calculations provided further mechanistic insights.

Strongly Directing Substituents in the Radical Arylation of Substituted Benzenes

Although general interest in radical arylation reactions has grown rapidly in recent years, poor regioselectivities and the need to use a large excess of the radical-accepting arene have hindered their application to substituted benzenes. We now describe experimental and computational investigations into the substituent effects that lead to regioselective addition based on the recent discovery of anilines as outstanding substrates for radical arylations.

Oxidative radical arylation of anilines with arylhydrazines and dioxygen from air

Substituted 2-aminobiphenyls have been prepared from arylhydrazine hydrochlorides and anilines in biphasic radical arylation reactions with dioxygen from air as a most simple and readily available oxidant. Under optimized conditions, the free amino functionality of the aniline leads to high ortho:meta regioselectivities, now even for anilines bearing a donor substituent in the para position. Finally, the mild and metal-free new access to aminobiphenyls was shown to be applicable on a gram scale.

Process for the Synthesis of Aminobiphenylene

The present invention relates to a process for the synthesis of 2-aminobiphenylene and derivatives thereof by reacting a benzene diazonium salt with an aniline compound under basic reaction conditions.

Regioselective radical arylation of anilines with arylhydrazines

Substituted 2-aminobiphenyls have been prepared from arylhydrazines and anilines via radical arylation reactions under simple oxidative conditions. The strong directing effect of the free and unprotonated amino functionality leads to high regioselectivities, and anilines have been shown to be significantly better aryl radical acceptors than nitrobenzenes or phenyl ethers. The methodology is also applicable to phenols, which react best as phenolates under strongly basic conditions. Finally, radical arylation reactions of anilines and anilinium salts under various conditions have for the first time demonstrated that regioselectivity can also be controlled through the rearomatization step and that the addition of an aryl radical to a substituted benzene might even be reversible.

The gomberg-bachmann reaction for the arylation of anilines with aryl diazotates

Simply aqueous sodium hydroxide is sufficient to exclude ionic side reactions and to prepare 2-aminobiphenyls from aryl diazotates and anilines through a new variant of the Gomberg-Bachmann reaction (see scheme). The metal-free reaction under basic conditions allows to exploit the highly radical-stabilizing effect of the aniline's free amino function for the first time, which leads to a so far unreached regioselectivity. Copyright

The gomberg-bachmann reaction for the arylation of anilines with aryl diazotates

Simply aqueous sodium hydroxide is sufficient to exclude ionic side reactions and to prepare 2-aminobiphenyls from aryl diazotates and anilines through a new variant of the Gomberg-Bachmann reaction (see scheme). The metal-free reaction under basic conditions allows to exploit the highly radical-stabilizing effect of the aniline's free amino function for the first time, which leads to a so far unreached regioselectivity. Copyright