48108-77-6

Usage

InChI:InChI=1/C8H8N2/c9-6-8(10)7-4-2-1-3-5-7/h1-5,8H,10H2/t8-/m1/s1

Upstream product

• 16750-42-8 2-amino-2-phenylacetonitrile 
• 160460-40-2 [(S)-1-(4-Methoxy-phenyl)-ethyl]-[1-phenyl-meth-(E)-ylidene]-amine 
• 1310539-57-1 C₂₀H₃₁N₄OP 
• 1236163-01-1 C₃₂H₂₉N₄OP 
• 228090-73-1 [(S)-1-(4-Methoxy-phenyl)-ethyl]-[1-phenyl-meth-(E)-ylidene]-amine 
• 100-52-7 benzaldehyde 
• 827308-21-4 (S)-[(S)-1-(4-Methoxy-phenyl)-ethylamino]-phenyl-acetonitrile 
• 345643-03-0 (S)-N-(phenylacetyl)-α-phenylglycinonitrile 
• 133870-88-9 (R)-2-(methanesulfonyloxy)-2-phenylacetonitrile 

Downstream Products

• 177723-19-2 (S)-2-N-tert-butoxycarbonylamino-2-phenylethanenitrile 
• 15028-39-4 L-2-phenylglycine methyl ester hydrochloride 

Relevant academic research and scientific papers

Process Optimisation Studies and Aminonitrile Substrate Evaluation of Rhodococcus erythropolis SET1, A Nitrile Hydrolyzing Bacterium

A comprehensive series of optimization studies including pH, solvent and temperature were completed on the nitrile hydrolyzing Rhodococcus erythropolis bacterium SET1 with the substrate 3-hydroxybutyronitrile. These identified temperature of 25 °C and pH of 7 as the best conditions to retain enantioselectivity and activity. The effect of the addition of organic solvents to the biotransformation mixture was also determined. The results of the study suggested that SET1 is suitable for use in selected organo-aqueous media at specific ratios only. The functional group tolerance of the isolate with unprotected and protected β-aminonitriles, structural analogues of β-hydroxynitriles was also investigated with disappointingly poor isolated yields and selectivity obtained. The isolate was further evaluated with the α- aminonitrile phenylglycinonitrile generating acid in excellent yield and ee (>99 % (S) – isomer and 50 % yield). A series of pH studies with this substrate indicated pH 7 to be the optimum pH to avoid product and substrate degradation.

Asymmetric strecker synthesis of α-arylglycines

A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure α-arylglycines has been developed. Addition of a range of aryl-aldehydes to a solution of sodium cyanide and (S)-1-(4- methoxyphenyl)ethylamine affords highly crystalline (S,S)-α-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-α-aminonitriles in 6 M aqueous HCl at reflux resulted in cleavage of their chiral auxiliary fragments and concomitant hydrolysis of their nitrile groups to afford enantiopure (S)-α-arylglycines. The enantiopurities of these (S)-α-arylglycines were determined via derivatization of their corresponding methyl esters with 2-formylphenylboronic acid and (S)-BINOL, followed by 1H NMR spectroscopic analysis of the resultant mixtures of diastereomeric iminoboronate esters.

The GAP chemistry for chiral N-phosphonyl imine-based Strecker reaction

Chiral N-phosphonyl imines were found to be efficient electrophiles for reaction with diethylaluminium cyanide, a non-volatile and inexpensive cyanide source. The reaction produced chiral Strecker adducts, α-aminonitriles, in excellent chemical yields (94-98%) and diastereoselectivities (95:5 to >99%). This synthesis was confirmed to follow the GAP chemistry (group-assistant-purification chemistry) process, which can avoid traditional chromatography and recrystallization purifications, i.e., the pure chiral α-aminonitriles bearing a chiral N-phosphonyl group can be simply obtained by washing the solid crude products with hexane. The chiral N-phosphonyl auxiliary can be easily cleaved under mildly acidic conditions and quantitatively recycled by a one-time extraction with n-butanol.

Asymmetric catalytic n -phosphonyl imine chemistry: The use of primary free amino acids and Et2AlCN for asymmetric catalytic strecker reaction

(Figure presented) The new asymmetric catalytic Strecker reaction of achiral N-phosphonyl imines has been established. Excellent enantioselectivity (95.2-99.7% ee) and yields (89-97%) have been achieved by using primary free natural amino acids as catalysts and Et2AlCN as nucleophile. This work also presents the novel use of nonvolatile and inexpensive Et 2AlCN in asymmetric catalysis. The N-phosphonyl protecting group enabled simple product purification to be achieved simply by washing the crude products with hexane, which is defined as the GAP chemistry (GAP: Group-Assistant-Purification).(17)It can also be readily cleaved and recycled under mild condition to give a quantitative recovery of N,N′- bis(naphthalen-1-ylmethyl)ethane-1,2-diamine. A new mechanism was proposed for this reaction and was supported by experimental observations.

Trimethylsilyl cyanide addition to aldimines and its application in the synthesis of (S)-phenylglycine methyl ester

The addition of TMSCN to a variety of arylaldimines (Strecker reaction) in the presence of LiClO4 or BF3?Et2O in acetonitrile has been studied. The reaction provided the addition products in very high yields. The method has been successfully utilized for the synthesis of (S)-phenylglycine methyl ester.

Resolution of (RS)-phenylglycinonitrile by penicillin acylase-catalyzed acylation in aqueous medium

A new strategy for the biocatalytic resolution of (R,S)-phenylglycinonitrile, a crucial intermediate in the antibiotic industry, has been developed. While former techniques exploit nitrilases or combinations of nitrile hydratases and amidases, manipulating with nitrile functionality, the current approach is based on a highly efficient and enantioselective acylation of the α-amino group with phenylacetic acid catalyzed by a well known enzyme, penicillin acylase from E. coli, in slightly acidic aqueous medium. It is shown that since the condensation product is poorly soluble, removal of (S)-phenylglycinonitrile from the reaction sphere is almost complete and irreversible, favoring kinetics of the process and making high conversion possible. The proposed approach is characterized by high space-time yield and extends the scope of enzymatic synthesis in aqueous medium.

A convenient synthesis of (S)-2-azidonitriles, (S)-2-aminonitriles and (S)-1,2-diamines

(S)-2-Azidonitriles (S)-4 are easily accessible from (R)-2-(sulfonyloxy)nitriles (R)-2 by nucleophilic substitution with alkali azides 3 under complete inversion of configuration. The azidonitriles (S)-4 can be converted by catalytic hydrogenation into (S)-2-aminonitriles (S)-8 and by hydrogenation using LiAlH4 into (S)-1,2-diaminoalkanes (S)-9, respectively, both, (S)-8 and (S)-9, isolated as hydrochlorides. Hydrolysis of the aminonitrile hydrochlorides (S)-8·HCl in a saturated solution of HCl in alcohol gives (S)-2-amino carboxamide hydrochlorides (S)-10·HCl with enantiomeric excesses >99% after recrystallization.

A CONVENIENT METHOD FOR OPTICAL RESOLUTIONS VIA DIASTEREOISOMERIC SALT FORMATION

With the advantage of the method using two immiscible solvents and half-equivalent amount of the resolving agent, higher optical purity can be obtained than in cases of any other resolution via diastereoisomeric salt formation, besides it is a faster procedure for resolution of a new racemate as well.

Quantitative Approaches to Optical Resolution. Part 1. Resolution of DL-Phenylglycine Derivatives with (+)-Tartaric Acid

The results of 23 cases of resolution of DL-phenyldlycine derivatives (I) with (+)-tartaric acid in various solvents are investigated, using correlation analysis, as a function of the introduced racemic compounds and the solvent used.A procedure, combining three quantitative structure-activity relationship methods, i.e.Golender and Rozenblit's logico-structural approach with the Free-Wilson and Hansch analyses, resulted in statistically significant relationships.It is suggested that the solvent may exert two kinds of influence: (1) the higher the solvent polarity, the more likely the L-(I) salt to crystallise; (2) alcoholic mixtures, although being highly polar, favour the precipitation of the D-(I) salt rather than that of the L-(I) salt, probably due to a selective interaction with the diastereomers.As to the racemic compound, the relationships obtained are in accord with literature statements that resolution proceeds by a multiple interaction mechanism.