81927-55-1

Basic information

• Product Name: BENZYL 2,2,2-TRICHLOROACETIMIDATE
• Synonyms: Benzyl 2,2,2-trichloroethanimidoate;Benzyl trichloroacetimidate;TRICHLOROACETIMIDIC ACID BENZYL ESTER;LABOTEST-BB LT00455324;BENZYL 2,2,2-TRICHLOROACETIMIDATE;2,2,2-TRICHLOROACETIMIDIC ACID BENZYL ESTER;Benzyl 2,2,2-trichloroacetimidate, 98+%;Ethanimidic acid, 2,2,2-trichloro-, phenylmethyl ester
• CAS NO: 81927-55-1
• Molecular Formula: C₉H₈Cl₃NO
• Molecular Weight: 252.52
• Product Categories: Benzene series;Protection & Derivatization Reagents (for Synthesis);Synthetic Organic Chemistry;Amidates/Imidates;Building Blocks;Chemical Synthesis;Nitrogen Compounds;Organic Building Blocks
• Mol File: 81927-55-1.mol

Chemical Properties

• Melting Point: 3 °C
• Boiling Point: 106-114 °C0.5 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless to yellow/Liquid
• Density: 1.359 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.001mmHg at 25°C
• Refractive Index: n20/D 1.545(lit.)
• Storage Temp.: 2-8°C
• Solubility: Miscible with cyclohexane/dichloromethane.
• PKA: 2.23±0.70(Predicted)
• Sensitive: Moisture Sensitive
• Stability: Moisture Sensitive
• BRN: 2525375
• CAS DataBase Reference: BENZYL 2,2,2-TRICHLOROACETIMIDATE(CAS DataBase Reference)
• NIST Chemistry Reference: BENZYL 2,2,2-TRICHLOROACETIMIDATE(81927-55-1)
• EPA Substance Registry System: BENZYL 2,2,2-TRICHLOROACETIMIDATE(81927-55-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26
• WGK Germany: 3
• F: 8-10-21
• Hazardous Substances Data: 81927-55-1(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
BENZYL 2,2,2-TRICHLOROACETIMIDATE is used as a reagent for the acid-catalyzed benzylation of hydroxy groups, which is an essential process in the synthesis of various organic compounds.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, BENZYL 2,2,2-TRICHLOROACETIMIDATE is used as a reagent during the synthesis of funiculosin dimethyl ether and (S)-3-(benzyloxy)-2-methylpropanal, which are important intermediates in the development of pharmaceutical products.
Used in Chemical Esterification:
BENZYL 2,2,2-TRICHLOROACETIMIDATE can also be used for mild esterification of carboxylic acids in the presence of a catalytic amount of BF3 etherate, which is a useful technique in organic chemistry for the formation of esters from carboxylic acids and alcohols.

Purification Methods

Purify the imidate by distillation to remove up to 1% of PhCH2OH as stabiliser. A solution in hexane can be stored for up to 2 months without decomposition. It is hygroscopic and has to be stored dry. [Wessel et al. J Chem Soc, Perkin Trans 1 2247 1985, Beilstein 6 IV 2265.]

InChI:InChI=1/C9H8Cl3NO/c10-9(11,12)8(13)14-6-7-4-2-1-3-5-7/h1-5,13H,6H2

Upstream product

• 545-06-2 trichloroacetonitrile 
• 100-51-6 benzyl alcohol 

Downstream Products

• 1707-92-2 tribenzylphosphate 
• 4257-83-4 benzyl 2,2,2-trichloroacetamide 
• 119788-82-8 (2R,5S)-3-Benzyloxy-5,6-dihydro-5-(3-hydroxypropyl)-2-methyl-2H-1,4-oxazin 
• 119788-83-9 (2R,5S)-5-(3-Benzyloxypropyl)-2-methyl-3-morpholinon 
• 119788-81-7 (2R,5S)-2-Methyl-5-(3-trichloracetimidoyloxypropyl)-3-morpholinon 
• 119788-86-2 (2R,5S)-3-(4-Benzyloxybutyloxy)-5-(3-hydroxypropyl)-2-methyl-5,6-dihydro-2H-1,4-oxazin 
• 119788-85-1 (2R,5S)-3-Benzyloxy-5-(3-benzyloxypropyl)-5,6-dihydro-2-methyl-2H-1,4-oxazin 
• 54555-84-9 benzyl iodoethyl ether 
• 594-65-0 trichloroacetamide 
• 148324-13-4 6-O-benzyl-5-deoxy-1,2-O-isopropylidene-3-O-methanesulfonyl-D-glucofuranose 
• 92949-51-4 allyl 2-acetamido-3,6-di-O-benzoyl-4-O-benzyl-2-deoxy-β-D-glucopyranoside 
• 79414-65-6 1,2,3,6-tetra-O-acetyl-4-O-benzyl-α-D-glucopyranose 
• 32780-08-8 (5S)-5-[(benzyloxy)methyl]dihydrofuran-2(3H)-one 
• 77697-15-5 (R)-(-)-γ-benzyloxymethyl-γ-butyrolactone 

Relevant articles and documents

Hit-to-lead optimization of novel benzimidazole phenylacetamides as broad spectrum trypanosomacides

Trypanosoma cruzi and Trypanosoma brucei are the parasitic causative agents of Chagas disease and human African trypanosomiasis (HAT), respectively. The drugs currently used to treat these diseases are not efficacious against all stages and/or parasite sub-species, often displaying side effects. Herein, we report the SAR exploration of a novel hit, 2-(4-chlorophenyl)-N-(1-propyl-1H-benzimidazol-2-yl)acetamide previously identified from high throughput screens against T. cruzi, Trypanosoma brucei brucei and Leishmania donovani. An informative set of analogues was synthesized incorporating key modifications of the scaffold resulting in improved potency whilst the majority of compounds retained low cytotoxicity against H9c2 and HEK293 cell lines. The SAR observed against T. cruzi broadly matches that observed against T.b. brucei, suggesting the possibility for a broad-spectrum candidate. This class of compounds therefore warrants further investigation towards development as a treatment for Chagas disease and HAT. This journal is

A Simple Method for the Preparation of Stainless and Highly Pure Trichloroacetimidates

We describe a method for obtaining various allylic, benzylic, and glucosyl 2,2,2-trichloroacetimidates (TCAIs) as stainless liquids or solids at the crude stage. The general synthetic method for the preparation of TCAIs often leads to stained products, and further purification of crude TCAIs causes decomposition due to their instability. In the described method, we use a solvent that barely dissolves the reactant, providing stainless and sufficiently pure TCAIs without requiring a purification step. Furthermore, the reaction mixture is turbid at the beginning and clear at the end, allowing us to monitor the progress of the reaction visually.

Synthesis of 3-deoxy-2-uloses via the indium-mediated allylation reaction

Abstract: We utilized the indium-mediated allylation reaction for the synthesis of carbohydrate structures containing the 3-deoxy-2-ulose motif, a barely investigated compound class. The stereoselective outcome can be controlled by the presence or absence of a chelating group in α-position to the carbonyl function. By introduction of an UV-active allyl building block, we enabled epimer separation by HPLC towards the synthesis of 3-deoxy-d-glycero-d-galacto-2-nonulose, the carboxyl-reduced analogue of widely distributed 3-deoxy-d-glycero-d-galacto-nonulosonic acid (Kdn). Ozonolysis of the introduced 2-C-methylidenepropan-1-ol motif provided the desired 3-deoxy-2-uloses. Graphical abstract: [Figure not available: see fulltext.].

New mannose derivatives: The tetrazole analogue of mannose-6-phosphate as angiogenesis inhibitor

Two novel compounds with mannose-derived structure, bearing a tetrazole (compound 3) and a sulfone group (compound 4) in terminal position, have been prepared from methyl α-d-mannopyranoside in reduced number of steps. The angiogenic activity of 3 and 4 has been screened using the chick chorioallantoic membrane (CAM) method. Tetrazole 3 has been identified to possess a promising bioactivity, being identified as angiogenesis inhibitor, with 68% of neovascular vessels when compared to control (PBS).

Br?nsted acid catalyzed monoalkylation of anilines with trichloroacetimidates

Trichloroacetimidates are useful alkylating agents for aromatic amines, requiring only a catalytic amount of a Br?nsted acid to facilitate the reaction. Monoalkylation predominates under these conditions. Electron-poor anilines provide superior yields, with electron-rich anilines sometimes showing competitive Friedel-Crafts alkylation. A single flask protocol with formation of the imidate in situ is demonstrated, providing a convenient method for the direct substitution of alcohols with anilines. Reaction with a chiral imidate favors a mechanism that proceeds through a carbocation intermediate.

Alkylation of thiols with trichloroacetimidates under neutral conditions

Trichloroacetimidates are displaced with thiols to form the corresponding sulfides without the need for an added acid or base by simply heating the reactants in refluxing THF. This operationally simple procedure provides the corresponding sulfides in excellent yields with only the formation of the neutral trichloroacetamide as the side product. The imidate may also be formed in situ, allowing for a direct method for the formation of sulfides from alcohols. This reaction provides a general method for the synthesis of a variety of sulfides from inexpensive and readily available alcohol starting materials.

A novel copper-catalyzed synthesis of functionalized alkynyl imidates and alkynyl thioimidates

A copper-catalyzed one-pot synthesis of alkynyl imidates and alkynyl thioimidates via coupling reactions of terminal alkynes with trichloroimidates, generated in situ from trichloroacetonitrile and benzyl alcohols or thiols, is reported.

Gold(I)-catalyzed arylmethylation of terminal alkynes

AuCl/AgOTf catalyzes the reaction of terminal alkynes with aryl trichloroacetimidate to afford arylmethylation products in moderate to good yields.

Gas-phase fragmentation of γ-lactone derivatives by electrospray ionization tandem mass spectrometry

Fragmentation reactions of β-hydroxymethyl-, β-acetoxymethyl- and β-benzyloxymethyl-butenolides and the corresponding γ-butyrolactones were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) using collision-induced dissociation (CID). This study revealed that loss of H2O [M+H-18]+ is the main fragmentation process for β-hydroxymethylbutenolide (1) and β-hydroxymethyl-γ- butyrolactone (2). Loss of ketene ([M+H-42]+) is the major fragmentation process for protonated β-acetoxymethyl-γ-butyrolactone (4), but not for β-acetoxymethylbutenolide (3). The benzyl cation (m/z 91) is the major ion in the ESI-MS/MS spectra of β-benzyloxymethylbutenolide (5) and β-benzyloxymethyl-γ-butyrolactone (6). The different side chain at the β-position and the double bond presence afforded some product ions that can be important for the structural identification of each compound. The energetic aspects involved in the protonation and gas-phase fragmentation processes were interpreted on the basis of thermochemical data obtained by computational quantum chemistry. Copyright

Total synthesis of discodermolide: Optimization of the effective synthetic route

An efficient and modulable total synthesis of discodermolide (DDM), a unique marine anticancer polyketide is described including related alternative synthetic approaches. Particularly notable is the repeated application of a crotyltitanation reaction to yield homoallylic (Z)-O-ene-carbamate alcohols with excellent selectivity. Advantage was taken of this reaction not only for the stereocontrolled building of the syn-anti methyl-hydroxy- methyl triads of DDM, but also for the direct construction of the terminal (Z)diene. Of particular interest is also the installation of the C13=C14 (Z)-double bond through a highly selective dyotropic rearrangement. The preparation of the middle C8-C14 fragment in two sequential stages and its coupling to the C1-C7 moiety was a real challenge and required careful optimization. Several synthetic routes were explored to allow high and reliable yields. Due to the flexibility and robust character of this approach, it might enable a systematic structural variation of DDM and, therefore, the elaboration and exploration of novel discodermolide structural analogues.