401-81-0

Basic information

• Product Name: 3-Iodobenzotrifluoride
• Synonyms: 3-iodo-α,α,α-trifluorotoluene;3-Iodobenzotrifluoride 99%;3-Iodobenzotrifluoride99%;3-Iodobenztrifluoride;3-idobenzotrifluoride;3-Iodobenzotrifluoride (stabilized with Copper chip);3-Iodo-a,a,a-trifluorotoluene;1-(Trifluoromethyl)-3-iodobenzene
• CAS NO: 401-81-0
• Molecular Formula: C₇H₄F₃I
• Molecular Weight: 272.01
• EINECS: 206-934-7
• Product Categories: Fluoro-contained Iodo series;Fluorine Compounds;Iodine Compounds;alkyl Iodine
• Mol File: 401-81-0.mol

Chemical Properties

• Melting Point: -8 °C
• Boiling Point: 82-82.5 °C25 mm Hg(lit.)
• Flash Point: 158 °F
• Appearance: Clear slightly yellow liquid
• Density: 1.887 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.04mmHg at 25°C
• Refractive Index: n20/D 1.517(lit.)
• Storage Temp.: 2-8°C(protect from light)
• Water Solubility: Insoluble
• Sensitive: Light Sensitive
• BRN: 2088596
• CAS DataBase Reference: 3-Iodobenzotrifluoride(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Iodobenzotrifluoride(401-81-0)
• EPA Substance Registry System: 3-Iodobenzotrifluoride(401-81-0)

Safety Data

• Hazard Codes: C,T,Xi
• Statements: 34-36/37/38
• Safety Statements: 26-27-36/37/39-45-37/39
• RIDADR: UN 3265 8/PG 2
• WGK Germany: 3
• TSCA: T
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 401-81-0(Hazardous Substances Data)

Usage

Uses

Used in Chemical Synthesis:
3-Iodobenzotrifluoride is used as a key intermediate in the synthesis of various organic compounds, particularly in the preparation of complex molecules with potential applications in different industries. Its reactivity in Sonogashira coupling reactions, a type of cross-coupling reaction, makes it a valuable building block for the construction of conjugated systems and molecular scaffolds.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 3-Iodobenzotrifluoride is used as a synthetic intermediate for the development of new drugs. Its unique structure allows for the creation of novel molecular entities with potential therapeutic applications.
Used in Material Science:
3-Iodobenzotrifluoride is also utilized in the field of material science, where it serves as a precursor for the development of advanced materials with specific properties, such as optoelectronic materials or specialty polymers.
Used in the Preparation of Zinc Porphyrins:
Specifically, 3-Iodobenzotrifluoride has been used in the preparation of zinc 5,10,15,20-tetrakis(3-(trifluoromethyl)phenylethynyl)porphyrin, a complex molecule with potential applications in areas such as photodynamic therapy, solar energy conversion, and molecular electronics. The Sonogashira coupling reaction between 3-iodobenzotrifluoride and phenylacetylene, facilitated by a palladium catalyst system, is a key step in the synthesis of this molecule.

InChI:InChI=1/C7H4F3I/c8-7(9,10)5-2-1-3-6(11)4-5/h1-4H

Upstream product

• 98-16-8 3-trifluoromethylaniline 
• 98-08-8 α,α,α-trifluorotoluene 
• 139-02-6 sodium phenoxide 
• 81447-72-5 m-(trifluoromethyl)diphenyliodonium iodide 
• 591-50-4 iodobenzene 
• 55642-42-7 bis(trifluoromethyl)tellurium 
• 401-78-5 3-bromo-1-trifluoromethylbenzene 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 1423-26-3 (meta-(trifluoromethyl)phenyl)boronic acid 
• 77152-08-0 trifluoromethylcopper(I) 
• 626-01-7 3-Iodoaniline 
• 76-05-1 trifluoroacetic acid 
• 3240-34-4 [bis(acetoxy)iodo]benzene 
• 454-87-5 3-(trifluoromethyl)benzenediazonium tetrafluoroborate 

Downstream Products

• 58313-23-8 3-iodobenzoic acid methyl ester 
• 393-10-2 4-iodo-1-nitro-2-(trifluoromethyl)benzene 
• 51571-29-0 1-[bis(trifluoroacetoxy)iodo]-3-(trifluoromethyl)benzene 
• 77326-90-0 4-<3-(trifluoromethyl)phenyl>-3-butyn-1-ol 
• 104483-70-7 3,3-dimethyl-1-(m-trifluoromethylphenyl)butan-2-one 
• 145439-11-8 3-(3-Trifluoromethylphenyl)furan-2(5H)-one 
• 145439-14-1 4-(3-trifluoromethylphenyl)-furan-2(5H)-one 
• 76783-59-0 ethyl 3-(trifluoromethyl)benzoate 
• 106336-12-3 3-trifluoromethyl-N,N-diphenylaniline 
• 98-08-8 α,α,α-trifluorotoluene 
• 64846-34-0 1-iodyl-3-trifluoromethylbenzene 
• 98-15-7 3-chlorotrifluoromethylbenzene 
• 41018-60-4 (3-(trifluoromethyl)phenyl)-λ3-iodanediyl diacetate 
• 603-34-9 N,N-diphenylaminobenzene 

Relevant articles and documents

Study on the degradation of the highly reactive hypervalent trifluoromethylation iodine reagent PhI(OAc)(CF3)

Degradation of the highly reactive hypervalent trifluoromethylation iodine reagent PhI(OAc)(CF3), which can only be generated in situ with mixing PhI(OAc)2 and TMSCF3 in the presence of CsF, was studied by ESI-MS and GC-MS combined with 19F-NMR. The important transient intermediate PhICF3+ was determined by ESI-MS, and the major volatile products containing CF3 were identified with the authentic compounds by using GC-MS, such as trifluoromethylbenzene, 2-iodobenzotrifluoride, 3-iodobenzotrifluoride, 4-iodobenzotrifluoride. Meanwhile, more evidences obtained with 19F-NMR were given for such degradation reaction. A possible rapid CF3 radical transfer reaction pathway was proposed to clarify such degradation progress based on the experimental results. Therefore, this study may be helpful in elucidating the intrinsic reactivity of PhI(OAc)(CF3) and the possible competing side reactions caused by such self-degradation pathway. Degradation of the highly reactive hypervalent trifluoromethylation iodine reagent PhI(OAc)(CF3), which can only be generated in situ with mixing PhI(OAc)2 and TMSCF3 in the presence of CsF, was studied by ESI-MS and GC-MS combined with 19F-NMR. The important transient intermediate PhICF3+ was determined by ESI-MS, and the major volatile products containing CF3 were identified with the authentic compounds by using GC-MS, such as trifluoromethylbenzene, 2-iodobenzotrifluoride, 3-iodobenzotrifluoride, 4-iodobenzotrifluoride. Meanwhile, more evidences obtained with 19F-NMR were given for such degradation reaction. A possible rapid CF3 radical transfer reaction pathway was proposed to clarify such degradation progress based on the experimental results. Therefore, this study may be helpful in elucidating the intrinsic reactivity of PhI(OAc)(CF3) and the possible competing side reactions caused by such self-degradation pathway.

Donor-activated lithiation and sodiation of trifluoromethylbenzene: Structural, spectroscopic, and theoretical insights

Aiming to shed new light on the stability and constitution of the organometallic intermediates involved in direct ortho-metalation processes, using trifluoromethylbenzene (1) as a case study, this paper investigates the deprotonation of 1 using group 1 alkyl bases tBuLi and nBuNa in the presence of the Lewis donors TMEDA (N,N,N′, N′-tetramethylethylenediamine), THF, and PMDETA (N,N,N′,N″, N″-pentamethyldiethylenetriamine). A systematic and comprehensive study combining structural, spectroscopic, and theoretical studies reveals that these donors strongly influence the final outcome of the reactions, not only by activating the alkali-metal bases and facilitating deprotonation of 1 but also by tuning the regioselectivity of the reaction. Thus, while using tBuLi/TMEDA, ortho-metalation of 1 is preferred, switching to THF gives a complex mixture of products with the meta-regioisomer being the major species crystallizing from hexane solution. This donor effect is significantly reduced when nBuNa is employed, as ortho-regioselectivity is observed almost exclusively using THF, TMEDA, or PMDETA. DFT calculations computing the relative energies of the ortho-, meta-, and para-regioisomers obtained from these metalating systems have also been carried out. Reinforcing the experimental findings, these theoretical studies show that although in all cases the product of ortho-metalation is the most thermodynamically preferred, the energy difference between the three possible modeled regioisomers is much larger for the Na systems than for the Li ones. The structures of key reaction intermediates [(TMEDA)·Li(C6H4-CF 3)]2 (2), [(TMEDA)·Na(C6H 4-CF3)]2 (3), and [(PMDETA)·Na(C 6H4-CF3)]2 (4) have been elucidated by X-ray crystallographic studies. All compounds exhibit a similar dimeric arrangement with a four-atom core constituting a {MCMC} ring. Interestingly for Na derivatives 3 and 4 unusual Na···F dative interactions are found, which appear to contribute to the overall stability of these compounds, therefore favoring ortho-metalation of 1, as the meta or para structures do not contain these additional interactions.

INHIBITOR OF BRUTON'S TYROSINE KINASE

Disclosed herein is a compound of Formula (I) with a Btk inhibitory activity, wherein all the variables are as defined herein. The compound can be used for the treatment of diseases such as autoimmune diseases, xenogeneic immune diseases, cancers or thromboembolic diseases. Also disclosed is a pharmaceutical composition comprising a compound of Formula (I). Futher provided is a compound capable of inhibiting the activity of Bruton's tyrosine kinase by covalent binding.

Base-catalyzed aryl halide isomerization enables the 4-selective substitution of 3-bromopyridines

The base-catalyzed isomerization of simple aryl halides is presented and utilized to achieve the 4-selective etherification, hydroxylation and amination of 3-bromopyridines. Mechanistic studies support isomerization of 3-bromopyridines to 4-bromopyridines proceedsviapyridyne intermediates and that 4-substitution selectivity is driven by a facile aromatic substitution reaction. Useful features of a tandem aryl halide isomerization/selective interception approach to aromatic functionalization are demonstrated. Example benefits include the use of readily available and stable 3-bromopyridines in place of less available and stable 4-halogenated congeners and the ability to converge mixtures of 3- and 5-bromopyridines to a single 4-substituted product.

Lipshutz-type bis(amido)argentates for directed: Ortho argentation

Bis(amido)argentate (TMP)2Ag(CN)Li2 (3, TMP-Ag-ate; TMP = 2,2,6,6-tetramethylpiperidido) was designed as a tool for chemoselective aromatic functionalization via unprecedented directed ortho argentation (DoAg). X-Ray crystallographic analysis showed that 3 takes a structure analogous to that of the corresponding Lipshutz cuprate. DoAg with this TMP-Ag-ate afforded multifunctional aromatics in high yields in processes that exhibited high chemoselectivity and compatibility with a wide range of functional groups. These included organometallics- A nd transition metal-susceptible substituents such as methyl ester, aldehyde, vinyl, iodo, (trifluoromethanesulfonyl)oxy and nitro groups. The arylargentates displayed good reactivity with various electrophiles. Chalcogen (S, Se, and Te) installation and azo coupling reactions also proceeded efficiently.

Cathodic C-H Trifluoromethylation of Arenes and Heteroarenes Enabled by an in Situ-Generated Triflyltriethylammonium Complex

While several trifluoromethylation reactions involving the electrochemical generation of CF3 radicals via anodic oxidation have been reported, the alternative cathodic, reductive radical generation has remained elusive. Herein, the first cathodic trifluoromethylation of arenes and heteroarenes is reported. The method is based on the electrochemical reduction of an unstable triflyltriethylammonium complex generated in situ from inexpensive triflyl chloride and triethylamine, which produces CF3 radicals that are trapped by the arenes on the cathode surface.

Direct Transformation of Arylamines to Aryl Halides via Sodium Nitrite and N-Halosuccinimide

A one-pot universal approach for transforming arylamines to aryl halides via reaction with sodium nitrite (NaNO2) and N-halosuccinimide (NXS) in DMF at room temperature under metal- and acid-free condition is described. This new protocol that is complementary to the Sandmeyer reaction, is suggested to involve the in situ generation of nitryl halide induce nitrosylation of aryl amine to form the diazo intermediate which is halogenated to furnish the aryl halide.

Rapid Iododeboronation with and without Gold Catalysis: Application to Radiolabelling of Arenes

Radiopharmaceuticals that incorporate radioactive iodine in combination with single-photon emission computed tomography imaging play a key role in nuclear medicine, with applications in drug development and disease diagnosis. Despite this importance, there are relatively few general methods for the incorporation of radioiodine into small molecules. This work reports a rapid air- and moisture-stable ipso-iododeboronation procedure that uses NIS in the non-toxic, green solvent dimethyl carbonate. The fast reaction and mild conditions of the gold-catalysed method led to the development of a highly efficient process for the radiolabelling of arenes, which constitutes the first example of an application of homogenous gold catalysis to selective radiosynthesis. This was exemplified by the efficient synthesis of radiolabelled meta-[125I]iodobenzylguanidine, a radiopharmaceutical that is used for the imaging and therapy of human norepinephrine transporter-expressing tumours.

Simple and Efficient Generation of Aryl Radicals from Aryl Triflates: Synthesis of Aryl Boronates and Aryl Iodides at Room Temperature

Despite the wide use of aryl radicals in organic synthesis, current methods to prepare them from aryl halides, carboxylic acids, boronic acids, and diazonium salts suffer from limitations. Aryl triflates, easily obtained from phenols, are promising aryl radical progenitors but remain elusive in this regard. Inspired by the single electron transfer process for aryl halides to access aryl radicals, we developed a simple and efficient protocol to convert aryl triflates to aryl radicals. Our success lies in exploiting sodium iodide as the soft electron donor assisted by light. This strategy enables the scalable synthesis of two types of important organic molecules, i.e., aryl boronates and aryl iodides, in good to high yields, with broad functional group compatibility in a transition-metal-free manner at room temperature. This protocol is anticipated to find potential applications in other aryl-radical-involved reactions by using aryl triflates as aryl radical precursors.

Easy Access to Difluoromethylene-Containing Arene Analogues through Palladium-Catalysed C–H Olefination

An efficient palladium-catalysed ortho-C–H olefination of α,α-difluorophenylacetic acid derivatives using 8-aminoquinoline as a bidentate directing group has been developed. A range of olefinated arenes can thus be synthesized in a concise way. This reaction provides an easy and straightforward route to a panel of difluoromethylated arene analogues in moderate to good yields, with a satisfactory tolerance of common functional groups. Transformation of the products into a variety of other difluoromethylene-containing compounds demonstrates the utility of this method.