346440-54-8

Basic information

• Product Name: (2S,5S)-(-)-2-TERT-BUTYL-3-METHYL-5-BENZYL-4-IMIDAZOLIDINONE
• Synonyms: MACMILLAN ORGANOCATALYST(TM) SS246;(2S,5S)-2-TERT-BUTYL-3-METHYL-5-BENZYL-&;(2S 5S)-2-(1' 1'-DIMETHYLETHYL)-3-METHY&;(2S,5S)-5-Benzyl-2-tert-butyl-3-methyl-4-imidazolidinone, (2S,5S)-2-tert-Butyl-3-methyl-5-phenylmethyl-4-imidazolidinone;(2S,5S)-()-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone,(2S,5S)-2-tert-Butyl-3-methyl-5-phenylmethyl-4-imidazolidinone, (2S,5S)-5-Benzyl-2-tert-butyl-3-methyl-4-imidazolidinone;(2S,5S)-5-Benzyl-2-(tert-butyl)-3-MethyliMidazolidin-4-one;(2S,5S)-(-)-2-tert-Butyl-3-Methyl-5-benzyl-4-iMidazolidinone 97%;(2S,5S)-(-)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone
• CAS NO: 346440-54-8
• Molecular Formula: C₁₅H₂₂N₂O
• Molecular Weight: 246.35
• Mol File: 346440-54-8.mol
• Article Data: 11

Chemical Properties

• Melting Point: 93-100 °C(lit.)
• Boiling Point: 378.0±35.0 °C(Predicted)
• Appearance: /
• Density: 1.040±0.06 g/cm3(Predicted)
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 5.59±0.60(Predicted)
• CAS DataBase Reference: (2S,5S)-(-)-2-TERT-BUTYL-3-METHYL-5-BENZYL-4-IMIDAZOLIDINONE(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,5S)-(-)-2-TERT-BUTYL-3-METHYL-5-BENZYL-4-IMIDAZOLIDINONE(346440-54-8)
• EPA Substance Registry System: (2S,5S)-(-)-2-TERT-BUTYL-3-METHYL-5-BENZYL-4-IMIDAZOLIDINONE(346440-54-8)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 346440-54-8(Hazardous Substances Data)

Usage

Uses

(2S,5S)-(-)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone is a second-generation MacMillan catalyst, which can be used as a chiral organocatalyst in: The chiral transformation reaction, including Friedel-Crafts and Mukaiyama-Michael reactions. The preparation of substituted spiroundecenetriones via asymmetric domino Knoevenagel/Diels-Alder reactions. The asymmetric synthesis of β-hydroxy aldehydes and their dimethylacetals via aldehyde-aldehyde aldol condensation reaction. The enantioselective α-fluorination of aldehydes using N-fluorobenzenesulfonamide as a fluorinating agent. The stereoselective preparation of (oxomethyl)oxabicyclo[3.2.1]octenones and tricyclic pyrroles via [4+3] cycloaddition of (trialkylsiloxy)pentadienals to furans.

General Description

(2S,5S)-(-)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone is a chiral imidazolidinone organocatalyst, developed by MacMillan and co-workers.

Synthetic route

L-phenylalanine methylamide (35373-92-3) + pivalaldehyde (630-19-3) → (2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride (691847-46-8) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
With ytterbium(III) triflate In chloroform for 8h; Inert atmosphere; Reflux;	A 58% B 11%
With ytterbium(III) triflate In chloroform at 20℃; for 8h;	A 58% B 11%
With ytterbium(III) triflate In chloroform for 8h; Reflux;	A 46% B 22%

L-phenylalanine methylamide (35373-92-3) + pivalaldehyde (630-19-3) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
With iron(III) chloride In tetrahydrofuran for 24h; Molecular sieve; Inert atmosphere; Reflux;	25%
With iron(III) chloride

(2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride (691847-46-8) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
With iron(III) chloride In tetrahydrofuran at 20℃; for 14h;	22%

(S)-N-(2',2'-Dimethylpropyliden)phenylalanin-(N-methylamid) → (2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride (691847-46-8) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
With hydrogenchloride In methanol 1.) 0 deg C, 30 min; 2.) room temp., 2 h; Yield given. Title compound not separated from byproducts;

methyl (2S)-2-amino-3-phenylpropanoate (2577-90-4) + m-Me-C6H4-CH2-Hal → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 82 percent / ethanol / 20 °C 2: FeCl3; 4 Angstroem molecular sieves / tetrahydrofuran / 36 h / 20 °C 3: 22 percent / FeCl3 / tetrahydrofuran / 14 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 82 percent / ethanol / 20 °C 2: 23 percent / FeCl3; 4 Angstroem molecular sieves / tetrahydrofuran / 36 h / 20 °C View Scheme

L-phenylalanine methylamide (35373-92-3) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: FeCl3; 4 Angstroem molecular sieves / tetrahydrofuran / 36 h / 20 °C 2: 22 percent / FeCl3 / tetrahydrofuran / 14 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 78 percent / pentane / Heating 2: HCl / methanol / 1.) 0 deg C, 30 min; 2.) room temp., 2 h View Scheme

methyl (2S)-2-amino-3-phenylpropanoate hydrochloride (7524-50-7) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: ethanol / 35 h 2: 78 percent / pentane / Heating 3: HCl / methanol / 1.) 0 deg C, 30 min; 2.) room temp., 2 h View Scheme
Multi-step reaction with 2 steps 1: ethanol / 48 h / 20 °C / Inert atmosphere 2: iron(III) chloride / tetrahydrofuran / 24 h / Molecular sieve; Inert atmosphere; Reflux View Scheme
Multi-step reaction with 2 steps 1: ethanol / 48 h / 20 °C 2: ytterbium(III) triflate / chloroform / 8 h / 20 °C View Scheme

(L)-phenylalanine ethyl ester hydrochloride (3182-93-2) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: ethanol / 35 h 2: 78 percent / pentane / Heating 3: HCl / methanol / 1.) 0 deg C, 30 min; 2.) room temp., 2 h View Scheme
Multi-step reaction with 2 steps 1: methylamine / ethanol / 95 h 2: ytterbium(III) triflate / chloroform / 8 h / Reflux View Scheme

pivalaldehyde (630-19-3) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / pentane / Heating 2: HCl / methanol / 1.) 0 deg C, 30 min; 2.) room temp., 2 h View Scheme

L-phenylalanine (63-91-2) → (2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride (691847-46-8) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 22 h / 0 °C / Reflux 2: ethanol / 23 h / 20 °C 3: ytterbium(III) triflate / chloroform / 8 h / Inert atmosphere; Reflux View Scheme

methyl (2S)-2-amino-3-phenylpropanoate hydrochloride (7524-50-7) → (2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride (691847-46-8) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / 23 h / 20 °C 2: ytterbium(III) triflate / chloroform / 8 h / Inert atmosphere; Reflux View Scheme

L-phenylalanine (63-91-2) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride; methanol 2: iron(III) chloride View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / 24 h / 20 °C 2: ethanol / 48 h / 20 °C 3: ytterbium(III) triflate / chloroform / 8 h / 20 °C View Scheme

C9H5N3O2*C15H22N2O → 2-(4-nitrophenyl)malononitrile (7077-65-8) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8)

Conditions	Yield
In acetonitrile at 20℃; Equilibrium constant; Inert atmosphere;

2-methoxyfuran (25414-22-6) + trans-Crotonaldehyde (123-73-9) + dichloroacetic acid (DCA) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → furan (110-00-9)

Conditions	Yield
In diethyl ether; chloroform	95%

2-methoxythiophene (16839-97-7) + trans-Crotonaldehyde (123-73-9) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → thiophene (188290-36-0)

Conditions	Yield
With trifluoroacetic acid In chloroform	92%

dichloro-acetic acid (79-43-6) + trans-Crotonaldehyde (123-73-9) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) + 1-(4-bromo-benzyl)-5-methoxy-2-methyl-1H-indole → (R)-3-[1-(4-bromo-benzyl)-5-methoxy-2-methyl-1H-indol-3-yl]-butanal (484638-53-1)

Conditions	Yield
In dichloromethane; isopropyl alcohol	87%

phenylacetaldehyde (122-78-1) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methyl-1-((E)-styryl)imidazolidin-4-one (1289555-78-7)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 2h; Reflux; Inert atmosphere;	87%

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) + methyl iodide (74-88-4) → C16H24N2O

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h;	78%

tetrafluoroboric acid diethyl ether (67969-82-8) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidin-1-ium Tetrafluoroborate (1646630-39-8)

Conditions	Yield
In diethyl ether at 0 - 20℃; for 0.333333h; Inert atmosphere;	67%

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → (2S,5S)-5-benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidin-1-ium hexafluorophosphate

Conditions	Yield
With hexafluorophosphoric acid In diethyl ether; water at 0 - 20℃; for 0.833333h; Inert atmosphere;	58%

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → (2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride (691847-46-8)

Conditions	Yield
With ytterbium(III) triflate In chloroform for 24h; Reflux;	56%

Octanal (124-13-0) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → C23H36N2O (1250294-79-1)

Conditions	Yield
With ammonium cerium (IV) nitrate In acetonitrile	23%

trifluorormethanesulfonic acid (1493-13-6) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one triflate

Conditions	Yield
In dichloromethane

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → BF4(1-)*C52H51F6N4O(1+)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 2 h / Reflux; Inert atmosphere 2: acetonitrile / 20 °C / UV-Vis spectroscopy instrument View Scheme

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → BF4(1-)*C42H47F6N4O(1+)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 2 h / Reflux; Inert atmosphere 2: acetonitrile / 20 °C / UV-Vis spectroscopy instrument View Scheme

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → BF4(1-)*C44H53N4O3(1+)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 2 h / Reflux; Inert atmosphere 2: acetonitrile / 20 °C / UV-Vis spectroscopy instrument View Scheme

2-(4-nitrophenyl)malononitrile (7077-65-8) + (2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) → C9H5N3O2*C15H22N2O

Conditions	Yield
In acetonitrile at 20℃; Equilibrium constant; Inert atmosphere;

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) + bis(4-(dimethylamino)phenyl)methylium tetrafluoroborate → C32H42N4O

Conditions	Yield
With 2,4,6-trimethyl-pyridine In acetonitrile at 20℃; Kinetics; Inert atmosphere;

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) + 4,4'-bis(morpholino)benzhydrylium tetrafluoroborate → C36H46N4O3

Conditions	Yield
With 2,4,6-trimethyl-pyridine In acetonitrile at 20℃; Kinetics; Inert atmosphere;

(2S,5S)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (346440-54-8) + bis[p-(methyl(2,2,2-trifluoroethyl)amino)]benzhydrylium tetrafluoroborate → C34H40F6N4O

Conditions	Yield
With 2,4,6-trimethyl-pyridine In acetonitrile at 20℃; Kinetics; Inert atmosphere;

Upstream product

• 691847-46-8 (2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride 
• 63-91-2 L-phenylalanine 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 35373-92-3 L-phenylalanine methylamide 
• 630-19-3 pivalaldehyde 
• 3182-93-2 (L)-phenylalanine ethyl ester hydrochloride 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 

Downstream Products

• 1646630-39-8 (2S,5S)-5-benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidin-1-ium Tetrafluoroborate 
• 691847-46-8 (2R,5S)-5-benzyl-2-tert-butyl-3-methylimidazolin-4-one hydrochloride 
• 188290-36-0 thiophene 
• 110-00-9 furan 
• 484638-53-1 (R)-3-[1-(4-bromo-benzyl)-5-methoxy-2-methyl-1H-indol-3-yl]-butanal 

Relevant articles and documents

Asymmetric hydroalkylation of alkynes and allenes with imidazolidinone derivatives: α-alkenylation of α-amino acids

This work reports a new method for the synthesis of quaternary α-alkenyl substituted amino acids by the enantio- and diastereoselective addition of imidazolidinone derivatives to alkynes and allenes. Further hydrolysis of the imidazolidinone products under acidic conditions afforded biologically relevant amino acid derivatives. This method is geometry-selective (E-isomer), enantio- and diastereoselective, and products were obtained in good to excellent yields. The utility of this new methodology is proved by its operational simplicity and the successful accomplishment of gram-scale reactions. Experimental and computational studies suggest the key role of Li in terms of selectivity and support the proposed reaction mechanism.

UNNATURAL AMINO ACIDS

The present invention relates to a process for the preparation compounds of Formula (I): Formula (I) wherein X, Z, Q, Ar, R1, R2, R3 and R4 are each as defined herein. The present invention also relates to processes for the preparation of the compounds of quaternary amino acids and hydantions, to compound of Formula(I), to intermediate compounds of Formula (II), to quaternary amino acid compounds of Formula (III) and to hydantoin compounds of Formula (IV).

Enantioselective oxidation of thioanisole to metyl phenyl sulfoxide by chiral compounds bearing N-Cl bond

Chiral sulfoxides are used in asymmetric synthesis and are present in various biologically active compounds. Asymmetric synthesis of the sulfoxides has been performed by chiral metal complexes and non-metals containing peroxide and oxide moieties. In this study, a new metal free method has been developed to oxidize thioanisole into methyl phenyl sulfoxide with easily accessible chiral compounds carrying N-Cl bond. For this purpose, chiral amine and amide bearing reagents were synthesized and chlorinated by using N-chlorosuccinimide. In oxidation reactions, chiral information has been transferred from N-chloramines to sulfides. With chlorinated chiral reagents, we observed enantioenriched sulfoxide formation. Although the observed results are promising, the best chiral amines are yet to be found. This is the first report on such a reaction, to the best of our knowledge.