63-91-2

Basic information

• Product Name: L-Phenylalanine
• Synonyms: L(-)-PHENYLALANINE;L-PHENYLALANINE;L-PHE;BETA-PHENYLALANINE;DL-2-AMINO-3-PHENYLPROPANOIC ACID;L-ALPHA-AMINO-BETA-PHENYLPROPIONIC ACID;L-BETA-PHENYLALANINE;L-2-AMINO-3-PHENYLPROPANOIC ACID
• CAS NO: 63-91-2
• Molecular Formula: C₉H₁₁NO₂
• Molecular Weight: 165.19
• EINECS: 200-568-1
• Product Categories: Food and Feed Additive;Amino ACIDS SERIES;API intermediates;Phenylalanine [Phe, F];Amino Acids and Derivatives;Amino Acids 13C, 2H, 15N;alpha-Amino Acids;Amino Acids;Biochemistry;Nutritional Supplements;L-Amino Acids;Amino Acids;Amino Acids & Derivatives;amino
• Mol File: 63-91-2.mol
• Article Data: 445

Chemical Properties

• Melting Point: 270-275 °C (dec.)(lit.)
• Boiling Point: 293.03°C (rough estimate)
• Flash Point: 139.8 °C
• Appearance: White to off-white/powder
• Density: 1.29
• Vapor Pressure: 7.09E-05mmHg at 25°C
• Refractive Index: -34 ° (C=2, H2O)
• Storage Temp.: Store at RT.
• Solubility: H2O: 0.1 M at 20 °C, clear, colorless
• PKA: 2.2(at 25℃)
• Water Solubility: 1-5 g/100 mL at 25 ºC
• Stability: Stable. Incompatible with strong oxidizing agents.
• Merck: 14,7271
• BRN: 1910408
• CAS DataBase Reference: L-Phenylalanine(CAS DataBase Reference)
• NIST Chemistry Reference: L-Phenylalanine(63-91-2)
• EPA Substance Registry System: L-Phenylalanine(63-91-2)

Safety Data

• Hazard Codes: C
• Statements: 36/37/38-34
• Safety Statements: 22-24/25-37/39-45-36/37/39-27-26
• WGK Germany: 3
• RTECS: AY7535000
• F: 10
• TSCA: Yes
• Hazardous Substances Data: 63-91-2(Hazardous Substances Data)

Usage

Description

L-Phenylalanine, an essential amino acid, is an odorless white crystalline powder with a slightly bitter taste. It is crucial for the production of proteins in the human body and is the precursor to L-tyrosine, which is further converted into neurotransmitters such as L-DOPA, dopamine, norepinephrine, and epinephrine. L-Phenylalanine is found in various natural sources, including beef, poultry, pork, fish, milk, yogurt, eggs, cheeses, soy products, and certain nuts and seeds.

Uses

1. Hair Care Industry:
L-Phenylalanine is used as a conditioning agent, with greater application in hair care than in skin care preparations. It helps improve the overall health and appearance of hair.
2. Suntan Products:
L-Phenylalanine is also used in suntan products, where it may enhance the effect of UVA radiation for people with vitiligo, potentially leading to darkening or repigmentation of white patches, particularly on the face.
3. Medical, Feed, and Nutritional Applications:
L-Phenylalanine is produced for various applications, including the preparation of Aspartame, a low-calorie artificial sweetener. It is also used as a nutritional supplement for its reputed analgesic and antidepressant effects.
4. Pharmaceutical Industry:
L-Phenylalanine is suggested as an intermediate for anti-cancer drugs, and a few small studies have shown promise in using it to manage alcohol withdrawal and ease PMS symptoms.
5. Food and Drink Industry:
L-Phenylalanine is used in the manufacture of food and drink products, as it affects neurotransmitters that help reduce hunger, improve memory, lessen the symptoms of ADHD and Parkinson's disease, and ease chronic pain.
6. Cocoa Substitute Industry:
According to FEMA, L-Phenylalanine is used in the cocoa substitute industry, where its chemical properties contribute to the overall flavor and quality of the product.

References

[1] http://www.umm.edu/health/medical/altmed/supplement/phenylalanine [2] Xueqin Song , Philip L. Lorenzi , Christopher P. Landowski , Balvinder S. Vig , John M. Hilfinger , Gordon L. Amidon (2005) Amino Acid Ester Prodrugs of the Anticancer Agent Gemcitabine:? Synthesis, Bioconversion, Metabolic Bioevasion, and hPEPT1-Mediated Transport, 2, 157-167.

Preparation

From PTS-negative Escherichia coli bioengineered strains.

Synthesis Reference(s)

Canadian Journal of Chemistry, 29, p. 427, 1951 DOI: 10.1139/v51-051The Journal of Organic Chemistry, 30, p. 3414, 1965 DOI: 10.1021/jo01021a035Tetrahedron Letters, 26, p. 2449, 1985 DOI: 10.1016/S0040-4039(00)94850-0

Air & Water Reactions

Water soluble. Aqueous solutions are weak acids.

Reactivity Profile

L-Phenylalanine may be light sensitive. Act as weak acids in solution.

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition L-Phenylalanine emits toxic fumes of nitrogen oxides.

Fire Hazard

Flash point data for L-Phenylalanine are not available; however, L-Phenylalanine is probably combustible.

Biochem/physiol Actions

L-Phenylalanine is an essential amino acid. It is significantly involved in the synthesis of neurotransmitters such as dopamine, epinephrine, norepinephrine, l-DOPA (Dihydroxyphenylalanine), melanin and thyroxine. L-Phenylalanine metabolism also results in phenylethylamine, that brings about effect of a stimulant in the brain and enhances mood.

Purification Methods

Likely impurities are leucine, valine, methionine and tyrosine. Crystallise L-phenylalanine from water by adding 4volumes of EtOH. Dry it in vacuo over P2O5. Also crystallise it from saturated refluxing aqueous solutions at neutral pH, or 1:1 (v/v) EtOH/water solution, or conc HCl. It sublimes at 176-184o/0.3mm with 98.7% recovery and unracemised [Gross & Gradsky J Am Chem Soc 77 1678 1955]. [Greenstein & Winitz The Chemistry of the Amino Acids J. Wiley, Vol 3 pp 2156-2175 1961, Beilstein 14 IV 1552.]

InChI:InChI:1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)

Synthetic route

methyl (2S)-2-amino-3-phenylpropanoate (2577-90-4) → L-phenylalanine (63-91-2)

Conditions	Yield
With ammonium bicarbonate; water In dichloromethane for 48h; α-chymotrypsin;	100%
With sodium hydroxide In water; ethyl acetate pH=9 - 10;	93%
at 25℃; for 0.833333h; enzyme alcalase from Bacillus licheniforms; pH 8.2;

N-Cbz-L-Phe (1161-13-3) → L-phenylalanine (63-91-2)

Conditions	Yield
With cell extract of Sphingomonas paucimobilis SC 16113 In water at 42℃; for 20h; Enzymatic reaction;	100%
With hydrogen In ethanol for 0.5h;	100%
With palladium on activated charcoal In methanol; ethyl acetate	99%

H-Phe-OEt (3081-24-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With ammonium bicarbonate; water In dichloromethane for 36h; α-chymotrypsin;	100%
With Tris buffer; water at 50℃; Rate constant;
With human valacyclovirase; water at 37℃; pH=7.4; Kinetics; Time; HEPES buffer; Enzymatic reaction;

((prop-2-yn-1-yloxy)carbonyl)-L-phenylalanine (439912-45-5) → L-phenylalanine (63-91-2)

Conditions	Yield
With resin bound tetrathiomolybdate In methanol at 28℃; for 1.5h; ultrasonic bath;	100%

2-oxo-3-(phenyl)propionic acid (156-06-9) → L-phenylalanine (63-91-2)

Conditions	Yield
With formate dehydrogenase; NAD; ammonium formate at 30℃; for 24h; PheDH;	99%
With A-(modified B6)-B-<ω-amino(ethylamino)>-β-cyclodextrin In water at 30℃; for 5h; pH 8.0 (phosphate buffer); Yield given;
With formate dehydrogenase; NAD; ammonium formate at 30℃; for 24h; Mechanism; buffer (pH 8.5); other oxo-acids; PheDH;

phenylalanine amide hydrochloride (108321-83-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With pyridoxal 5'-phosphate monohydrate; cobalt(II) chloride In aq. buffer at 40℃; for 4h; pH=7.0; Enzymatic reaction;	99%

(S)-2-acetylamino-3-phenylpropanoic acid (2018-61-3) → L-phenylalanine (63-91-2)

Conditions	Yield
With pepsin immobilized on terephthalaldehyde functionalized chitosan magnetic nanoparticle In acetonitrile at 20℃; for 48h; pH=2;	98%
With hydrogenchloride
With hydrogen bromide

phenylpyruvate- (620-76-8) → L-phenylalanine (63-91-2)

Conditions	Yield
With ammonium formate; tris hydrochloride; nicotinamide adenine dinucleotide; formate dehydrogenase; phenylalanine dehydrogenase In water at 30℃; for 24h;	98%
With ammonium formate; tris hydrochloride; nicotinamide adenine dinucleotide; phenylalanine and formate dehydrogenase In water at 30℃; for 24h; Equilibrium constant; pH = 8.5;	98%
With L-glutamic acid; pyridoxal 5'-phosphate In water at 40℃; for 12h; E.coli Aspartate transaminase, pH 8;	84%
With L-glutamic acid; E.coli Aspartate transaminase; pyridoxal 5'-phosphate at 40℃; for 12h; enzyme kinetics; pH 8; Miachaelis constant (Km); maximum velocity constant (vmax); further α-keto acids;	84%
With L-glutamine; human glutamine transaminase K at 37℃; pH=7.4; aq. phosphate buffer; Enzymatic reaction;

((S)-1-Cyano-2-phenyl-ethyl)-carbamic acid methyl ester (631921-67-0) → L-phenylalanine (63-91-2)

Conditions	Yield
With hydrogenchloride In water for 7h; Heating;	98%

(S)-2-hydrazinyl-3-phenylpropanoic acid (1202-31-9) → L-phenylalanine (63-91-2)

Conditions	Yield
With hydrogen; nickel In water; acetic acid under 25857.4 Torr;	97%

(S)-2-{1-[4-Nitro-1,3-dioxo-indan-(2E)-ylidene]-ethylamino}-3-phenyl-propionic acid → L-phenylalanine (63-91-2) + 2-[1-Hydrazino-eth-(E)-ylidene]-4-nitro-indan-1,3-dione

Conditions	Yield
With hydrazine hydrate In ethanol for 3h; Ambient temperature;	A n/a B 97%

Phenylalanine (150-30-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With D-amino acid oxidase; E. coli branched-chain amino acid aminotransferase In water at 37℃; for 72h; Tris buffer, pH 8.5, 1mM EDTA, monosodium glutamate, bovine serum albumin, catalase, pyridoxal 5'-phosphate;	96%
With porcine kidney D-amino acid oxidase (EC 1.4.3.3.); sodium cyanoborohydride; flavin adenine dinucleotide In phosphate buffer at 37℃;	82%
With sodium hydroxide; oxygen at 30℃; for 24h; pH=7.3; aq. buffer; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;	44%

N-allyloxycarbonyl-(S)-phenylalanate (90508-20-6) → L-phenylalanine (63-91-2)

Conditions	Yield
With tri-n-butyl-tin hydride; bis-triphenylphosphine-palladium(II) chloride In dichloromethane Ambient temperature;	95%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → L-phenylalanine (63-91-2)

Conditions	Yield
With tetradecyl(trihexyl)phosphonium bistriflamide; trifluoroacetic acid at 130℃; for 0.166667h; Ionic liquid;	95%
With methanol; tetrachloromethane at 20℃; for 12h; UV-irradiation;	91%
With trifluoroacetic acid
With ethylenediaminetetraacetic acid; phenylmethylsulphonyl fluoride; water In aq. phosphate buffer at 30℃; Kinetics; Reagent/catalyst; Microbiological reaction; Enzymatic reaction;
With trifluoroacetic acid at 20℃; for 0.25h;

benzyl bromide (100-39-0) → L-phenylalanine (63-91-2)

Conditions	Yield
	95%
Multi-step reaction with 2 steps 1: 1.) LDA / 1.) THF, hexane, from -78 deg C to -20 deg C; 2.) THF, from -78 deg C to -20 deg C, 24 h 2: 92 percent / 1 N aq. HCl / 4 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 1.) sodium bis(trimethylsilyl)amide / 1.) THF, -82 deg C, 40 min, 2.) THF, -82 deg C, 1.5 h 2: 80 percent / trifluoroacetic acid / CH2Cl2 / 4 h 3: 76 percent / H2 / PdCl2 / tetrahydrofuran; ethanol / 29 h / 2172.02 Torr View Scheme
Multi-step reaction with 2 steps 1: 1.) LDA / 1.) THF, -78 deg C, 2.) THF, -78 deg C 2: 85 percent / 6N HCl / 6 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 77 percent / NaN(Si(CH3)3)2 / tetrahydrofuran / 0.67 h / -100 °C 2: 1) TFA; 2) H2 / 2) Pd / 1) CH2Cl2 View Scheme

N-Fmoc L-Phe (35661-40-6) → L-phenylalanine (63-91-2)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 50℃; for 1h; Temperature; Time; Solvent;	95%
Stage #1: N-Fmoc L-Phe With N-ethyl-N,N-diisopropylamine In dichloromethane for 1h; 2-chlorotrityl chloride resin; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.166667h; 2-chlorotrityl chloride resin; Stage #3: With trifluoroacetic acid In dichloromethane for 0.166667h;
With piperidine In N,N-dimethyl-formamide for 0.0333333h; Solvent;

C34H29Cl2N3NiO3 → L-phenylalanine (63-91-2) + (S)-1-benzyl-N-[4-chloro-2-(2-chlorobenzoyl)phenyl]pyrrolidine-2-carboxamide (1616841-99-6)

Conditions	Yield
Stage #1: C34H29Cl2N3NiO3 With hydrogenchloride In 1,4-dioxane; methanol; water at 60℃; Stage #2: In 1,4-dioxane; methanol; water enantioselective reaction;	A 72% B 95%

D-Phenylalaninamide (5241-58-7, 5241-59-8, 17193-31-6, 60058-39-1) + butan-1-ol (71-36-3) → L-phenylalanine (63-91-2)

Conditions	Yield
	94%

(3S,6S,8S,8aS)-3-benzyl-7,7,8a-trimethyl-3,5,6,7,8,8a-hexahydro-2H-6,8-methanobenzo[b][1,4]oxazin-2-one (141895-40-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran at 70℃; for 3h;	93%

(S)-4'-benzyl-9λ4-boraspiro[bicyclo[3.3.1]nonane-9,2'-[1,3,2]oxazaborolidin]-5'-one → L-phenylalanine (63-91-2)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran; water at 20℃; for 1h; Reagent/catalyst; Temperature; Solvent;	93%
With peracetic acid; disodium hydrogenphosphate In dichloromethane at 20℃; Reagent/catalyst;

Upstream product

• 75719-90-3 2,3,4,6-tetra-O-benzyl-1-O-(N-benzyloxycarbonylglycylglycyl-L,D-phenylalanyl)-α-D-glucopyranose 
• 484-42-4 angiotensin I 
• 5619-07-8 methyl 2-amino-3-phenylpropanoate hydrochloride 
• 117470-84-5 2-{[1-(4-Chloro-phenyl)-meth-(Z)-ylidene]-amino}-3-phenyl-propionic acid ethyl ester 
• 15028-44-1 DL-phenylalanine methyl ester 
• 37466-27-6 4-([(1S)-1-carboxy-2-phenylethyl]carbamoyl)butanoic acid 
• 7647-01-0 hydrogenchloride 
• 16364-51-5 N-(N-acetyl-phenylalanyl)-glutamic acid 
• 223755-94-0 1-methyl-(3S)-benzyl-4-<(S)-α-phenylethyl>-1,4,benzodiazepine-2,5-dione 
• 21195-40-4 2-(2-chloro-acetylamino)-3-phenyl-acrylic acid 
• 147780-58-3 (3S,5S)-3-benzyl-5-phenyl-3,4,5,6-tetrahydro-1,4-oxazin-2-one 
• 61090-95-7 (S)-2-[(S)-2-(2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-propionylamino}-acetylamino)-3-phenyl-propionylamino]-4-methylsulfanyl-butyramide 
• 190059-40-6 [(S)-1-Benzyl-2-((3aS,8aR)-2,2-dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-3-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 
• 188591-76-6 tert-butyl (2,2,2-trifluoroacetyl)-L-phenylalaninate 

Downstream Products

• 100610-68-2 (S)-2-(1,1-dioxo-1λ⁶-thiomorpholino)-3-phenyl-propionic acid 
• 96789-63-8 N-(o-carboxybenzoyl)-L-phenylalanine 
• 5123-55-7 Nα-phthaloyl-L-phenylalanine 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 859-45-0 N-trifluoroacetyl-leucylphenylalanine methylester 
• 23635-30-5 (S)-(-)-methyl N-(trifluoroacetyl)phenylalaninate 
• 350-09-4 N-trifluoroacetyl-L-phenylalanine 
• 37628-66-3 (S)-2-(2-oxo-4,5-diphenyl-oxazol-3-yl)-3-phenyl-propionic acid 
• 66851-63-6 (S)-2-[4,5-bis-(4-methoxy-phenyl)-2-oxo-oxazol-3-yl]-3-phenyl-propionic acid 
• 1170-76-9 Z-Gly-(L)-Phe 
• 99104-29-7 (S)-4-benzyl-2,2-bis-(chloro-difluoro-methyl)-oxazolidin-5-one 
• 83793-92-4 (S)-2-[2-(2-Chloro-phenoxymethyl)-4-oxo-4H-quinazolin-3-yl]-3-phenyl-propionic acid 
• 3081-24-1 H-Phe-OEt 
• 86334-92-1 N-(1-deoxy-D-fructos-1-yl)-L-phenylalanine 

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