132-98-9

Basic information

• Product Name: Penicillin V potassium salt
• Synonyms: PHENOXYMETHYLPENICILLINIC ACID POTASSIUM SALT;PHENOXYMETHYLPENICILLIN K+ SALT;PHENOXYMETHYLPENICILLIN POTASSIUM;PHENOXYMETHYL PENICILLIN POTASSIUM SALT;PENICILLIN VK;PENICILLIN V POTASSIUM;PENICILLIN V POTASSIUM SALT;PENICILLIN V
• CAS NO: 132-98-9
• Molecular Formula: C₁₆H₁₇N₂O₅S*K
• Molecular Weight: 388.48
• EINECS: 205-086-5
• Product Categories: Peptide Synthesis/Antibiotics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;NULL;BEEPEN-VK;antibiotic;Inhibitors
• Mol File: 132-98-9.mol
• Article Data: 2

Chemical Properties

• Melting Point: 197-202°C
• Boiling Point: 681.4 °C at 760 mmHg
• Flash Point: 365.9 °C
• Appearance: Odorless white crystalline powder
• Density: 1.40
• Vapor Pressure: 1.69E-19mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: Freely soluble in water, practically insoluble in ethanol (96 per cent).
• Water Solubility: Soluble in water, dimethyl sulfoxide, and methanol.
• Stability: Hygroscopic
• BRN: 3899451
• CAS DataBase Reference: Penicillin V potassium salt(CAS DataBase Reference)
• NIST Chemistry Reference: Penicillin V potassium salt(132-98-9)
• EPA Substance Registry System: Penicillin V potassium salt(132-98-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22-42/43
• Safety Statements: 22-26-36/37-45
• WGK Germany: 3
• RTECS: XH9275000
• TSCA: Yes
• Hazardous Substances Data: 132-98-9(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline Solid

Originator

Oracilline ,Theraplix ,France ,1954

Uses

Different sources of media describe the Uses of 132-98-9 differently. You can refer to the following data:
1. Penicillin V Potassium bactericidal against penicillin-susceptible microorganisms during the stage of active multiplication. It inhibits biosynthesis of cell-wall mucopeptide. It is used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
2. Penicillin antibacterial.

Manufacturing Process

The following description is taken from US Patent 2,941,995. A solution of phenoxyacetyl chloride (360 mg) in dry acetone (5 ml) was added dropwise during 10 minutes to a stirred solution of 6-aminopenicillanic acid (450 mg, approximately 75% pure) in 3% aqueous bicarbonate (18 ml), and acetone (12 ml). When addition was complete the mixture was stirred at room temperature for 30 minutes and then extracted with ether (30 ml in 3 portions), only the aqueous phase being retained. This aqueous solution was covered with butanol (5 ml) and adjusted to pH 2 by the addition of N hydrochloric acid. After separating the layers, the aqueous phase was extracted with two 2.5 ml portions of butanol, adjusting to pH 2 each time. The combined butanol solutions (which at this stage contained the free penicillanic acid) were washed with water (3 x 2 ml) and then shaken with water (10 ml) to which sufficient 3% sodium bicarbonate solution was added to bring the aqueous phase to pH 7. The butanol solution was further extracted with two 5 ml portions of water to each of which was added enough bicarbonate solution to produce an aqueous phase of pH 7. The combined aqueous solutions were washed with ether (20 ml) and then evaporated at low temperature and pressure to leave the crude sodium salt of phenoxymethyl penicillin which, after drying in a vacuum desiccator, was obtained as a slightly hygroscopic powder (591 mg).

Brand name

V-Cillin(Lilly).

Therapeutic Function

Antibacterial

General Description

Odorless white crystalline powder. Slightly bitter taste. pH (0.5% aqueous solution) 5 to 7.5.

Air & Water Reactions

Water soluble.

Reactivity Profile

Penicillin V potassium salt is the potassium salt of penicillin v. Penicillin V potassium salt is incompatible with acids, oxidizing agents (especially in the presence of trace metals), heavy metal ions such as copper, lead, zinc and mercury; glycerol, sympathomimetic amines, thiomersal, wood alcohols, cetostearyl alcohol, hard paraffins, macrogols, cocoa butter and many ionic an nonionic surface-active agents. Penicillin V potassium salt is also incompatible with alkalis, compounds leached from vulcanized rubber, hydrochlorides of tetracyclines and organic peroxides. Other incompatibilities include reducing agents, alcohols, other hydroxy compounds, self-emulsifying stearyl alcohol, emulsifying wax, lanolin, crude cholinesterated bases, glycol, sugars, amines, aminacrine hydrochloride, ephedrine, procaine, rubber tubing, thiamine hydrochloride, zinc oxide, oxidized cellulose, iodine, iodides, thiols, chlorocresol and resorcinol. Penicillin V potassium salt may also be incompatible with naphthalene oils and vitamin B.

Fire Hazard

Flash point data for Penicillin V potassium salt are not available; however, Penicillin V potassium salt is probably combustible.

Safety Profile

Moderately toxic by ingestion, intramuscular, intraperitoneal, and intravenous routes. Human mutation data reported. Questionable carcinogen with no experimental evidence. When heated to decomposition it emits very toxic fumes of NOx, K2O, and SOx. Used

InChI:InChI=1/C16H18N2O5S/c1-16(2)12(15(21)22)18-13(20)11(14(18)24-16)17-10(19)8-23-9-6-4-3-5-7-9/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22)/p-1/t11-,12+,14-/m1/s1

Synthetic route

potassium 2-ethylhexanoate + penicilin V (87-08-1) → penicillin V potassium (132-98-9)

Conditions	Yield
In butan-1-ol	80%

6-Aminopenicillanic Acid (551-16-6) + Phenoxyacetyl chloride (701-99-5) → penicillin V potassium (132-98-9)

Conditions	Yield
Stage #1: 6-Aminopenicillanic Acid; Phenoxyacetyl chloride With sodium hydrogencarbonate In water; acetone at 10 - 15℃; for 0.333333h; Stage #2: With potassium 2-ethylhexanoate In butan-1-ol	80%

6-Aminopenicillanic Acid (551-16-6) → penicillin V potassium (132-98-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water; acetone / 0.35 h / 10 - 15 °C 1.2: pH 2 2.1: butan-1-ol View Scheme

Phenoxyacetyl chloride (701-99-5) → penicillin V potassium (132-98-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water; acetone / 0.35 h / 10 - 15 °C 1.2: pH 2 2.1: butan-1-ol View Scheme

penicillin V potassium (132-98-9) + 1-bromomethyl-4-nitro-benzene (100-11-8) → 4-nitrobenzyl(2S,5R,6R)-3,3-dimethyl-7-oxo-6-phenoxyacetamido-1-aza-4-thiabicyclo<3.2.0>heptane-2-carboxylate (58244-55-6)

Conditions	Yield
With sodium iodide In N,N-dimethyl-formamide for 15h; Ambient temperature;	97%

benzyl bromide (100-39-0) + penicillin V potassium (132-98-9) → (2S,5R,6R)-benzyl-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate (1256-06-0)

Conditions	Yield
In N,N-dimethyl-formamide for 24h; Ambient temperature;	95%
In N,N-dimethyl-formamide Ambient temperature;

C56H135ClN4Si7(4+)*4I(1-) + penicillin V potassium (132-98-9) → C72H152N6O5SSi7(4+)*4I(1-)

Conditions	Yield
With 18-crown-6 ether; sodium iodide In N,N-dimethyl-formamide at 100℃; for 40h; Inert atmosphere; Sealed tube;	95%

penicillin V potassium (132-98-9) + methyl iodide (74-88-4) → methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate (2315-05-1)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 17h;	94%
In N,N-dimethyl-formamide at 20℃; for 1h;	65%
In N,N-dimethyl-formamide at 20℃; for 12h;	63%

Chloromethyl acetate (625-56-9) + penicillin V potassium (132-98-9) → acetoxymethyl 6-(phenoxyacetamido)-penicillinate (72842-44-5)

Conditions	Yield
In dimethyl sulfoxide for 20h; Ambient temperature;	92%

C26H63ClN2Si3(2+)*2I(1-) + penicillin V potassium (132-98-9) → C42H80N4O5SSi3(2+)*2I(1-)

Conditions	Yield
With 18-crown-6 ether; sodium iodide In N,N-dimethyl-formamide at 80℃; for 40h; Inert atmosphere; Sealed tube;	89%

penicillin V potassium (132-98-9) + 5,11,17,23-tetra(tert-butyl)-25,27-bis-(3-hydroxypropoxy)-26,28-bis-hydroxycalix[4]arene → C82H100N4O14S2

Conditions	Yield
In N,N-dimethyl-formamide at 40℃; for 42h; Inert atmosphere;	32%

diazomethane (186581-53-3, 908094-01-9) + penicillin V potassium (132-98-9) → (3S,5R,6R)-3-diazoacetyl-2,2-dimethyl-6-phenoxyacetamidopenam (15583-33-2)

Conditions	Yield
(i) SOCl2, CHCl3, (ii) /BRN= 102415/; Multistep reaction;
With chloroformic acid ethyl ester; triethylamine hydrochloride 1.) CH2Cl2, (CCl4-solid CO2), 1.25 h, 2.) Et2O, 0 deg C, 1.5 h; Yield given. Multistep reaction;

2-acetyl-benzoic acid (577-56-0) + penicillin V potassium (132-98-9) → 6β-(2-phenoxy-acetylamino)-penicillanic acid (Ξ)-1-methyl-3-oxo-1,3-dihydro-isobenzofuran-1-yl ester (55361-58-5)

Conditions	Yield
(i) Py, PhSO2Cl, (ii) /BRN= 3899450/; Multistep reaction;

3-Bromophthalide (6940-49-4) + penicillin V potassium (132-98-9) → 6β-(2-phenoxy-acetylamino)-penicillanic acid (Ξ)-3-oxo-1,3-dihydro-isobenzofuran-1-yl ester (60158-36-3)

Conditions	Yield
In N,N-dimethyl-formamide

1-butanethiol (109-79-5) + penicillin V potassium (132-98-9) → (5R)-3,3-dimethyl-7-oxo-6t-(2-phenoxy-acetylamino)-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carbothioic acid S-butyl ester (69577-99-7)

Conditions	Yield
With potassium carbonate In 1,2-dimethoxyethane Ambient temperature;

sulfure de methyle et de 2-chloroethyle (542-81-4) + penicillin V potassium (132-98-9) → 6β-(2-phenoxy-acetylamino)-penicillanic acid 2-methylsulfanyl-ethyl ester (66260-34-2)

Conditions	Yield
In N,N-dimethyl-formamide

penicillin V potassium (132-98-9) → (5R)-3,3-dimethyl-7-oxo-6t-(2-phenoxy-acetylamino)-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carbothioic acid

Conditions	Yield
(i) Et3N*HCl, CH2Cl2, (ii) ClCO2Et, DMF, (iii) NaSH; Multistep reaction;

penicillin V potassium (132-98-9) + thiophenol (108-98-5) → (5R)-3,3-dimethyl-7-oxo-6t-(2-phenoxy-acetylamino)-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carbothioic acid S-phenyl ester (69577-98-6)

Conditions	Yield
With potassium carbonate In 1,2-dimethoxyethane Ambient temperature;

penicillin V potassium (132-98-9) + ethanethiol (75-08-1) → (5R)-3,3-dimethyl-7-oxo-6t-(2-phenoxy-acetylamino)-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carbothioic acid S-ethyl ester (69577-97-5)

Conditions	Yield
With potassium carbonate In 1,2-dimethoxyethane Ambient temperature;

1-chloroethyl phenyl ether (10477-40-4) + penicillin V potassium (132-98-9) → penicillin V, 1-(phenoxy)ethyl ester

Conditions	Yield
at 0℃; Yield given;

ciprofloxacin (85721-33-1) + penicillin V potassium (132-98-9) → 1-Cyclopropyl-7-{4-[(2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-piperazin-1-yl}-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid

Conditions	Yield
With chloroformic acid ethyl ester; 4-methyl-morpholine 1.) CH2Cl2, -7 to -10 deg C, 45 min, 2.) CH2Cl2, MeOH, -5 to 0 deg C, 2 h; Yield given. Multistep reaction;

penicillin V potassium (132-98-9) + N,N-dibenzylamine hydrochloride (20455-68-9) → penicillin V dibenzylamine salt (121527-61-5)

Conditions	Yield
With potassium phenoxyacetate In water at 5℃;	692 mg

penicillin V potassium (132-98-9) → (R)-3-Methyl-2-[(S)-2-oxo-3-(2-phenoxy-acetylamino)-azetidin-1-yl]-but-3-enoic acid (87796-73-4) + (R)-α-[(S)-2-oxo-3-(2-phenoxy-acetylamino)-azetidin-1-yl]-isovaleric acid (87796-74-5)

Conditions	Yield
With nickel In water at 165℃; for 0.25h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With nickel In water at 165℃; for 0.25h; Yield given. Yields of byproduct given;

penicillin V potassium (132-98-9) + 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (70458-96-7) → 7-{4-[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-piperazin-1-yl}-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid

Conditions	Yield
With chloroformic acid ethyl ester; 4-methyl-morpholine 1.) CH2Cl2, -7 to -10 deg C, 45 min, 2.) CH2Cl2, MeOH, -5 to 0 deg C, 2 h; Yield given. Multistep reaction;

penicillin V potassium (132-98-9) + chloroacetone (78-95-5) → (2S,4S,5R,6R)-3,3-Dimethyl-4,7-dioxo-6-(2-phenoxy-acetylamino)-4λ4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 2-oxo-propyl ester (72881-16-4)

Conditions	Yield
With sodium periodate Yield given. Multistep reaction;

Upstream product

• 551-16-6 6-Aminopenicillanic Acid 
• 87-08-1 penicilin V 
• 701-99-5 Phenoxyacetyl chloride 

Downstream Products

• 100410-47-7 6-phenoxyacetacetamidopenicillanicacid 2-(diethylamino)ethyl ester hydrochloride 
• 66260-35-3 dimethyl-{2-[6β-(2-phenoxy-acetylamino)-penicillanoyloxy]-ethyl}-sulfonium; iodide 
• 89971-88-0 benzyl (3S,5R,6R)-6-phenoxyacetamido-penicillanate 1,1-dioxide 
• 39650-26-5 phenoxymethylpenicillinic acid 1,1-dioxide 
• 4052-69-1 penicillin-V β-sulfoxide benzyl ester 
• 4888-90-8 phenoxymethylpenicillin sulfoxide 
• 51887-18-4 1ξ-oxo-6β-(2-phenoxy-acetylamino)-1λ⁴-penicillanic acid 2,2-dimethyl-propionyloxymethyl ester 
• 51415-85-1 (pivaloyloxy)methyl 3-methyl-7-(2-phenoxyacetamido)ceph-3-em-4-carboxylate 
• 119618-13-2 (7R,8S)-2-isopropylidene-8-phenoxyacetamido-5-oxa-6-thia-1-azabicyclo<5.2.0>nonane-3,9-dione 6-oxide 
• 118673-32-8 (7R,8R)-2-isopropylidene-8-phenoxyacetamido-5-oxa-6-thia-1-azabicyclo<5.2.0>nonane-3,9-dione 6-oxide 

Relevant articles and documents

Synthesis of new penicillin derivatives as drug-like molecules for biological screening

Chemical modification of penicillin β-lactam ring was made. Six thiazolidine amides were produced through N4-C7 β-lactam ring opening of penicillin V methyl ester with various aliphatic, aromatic, and heterocyclic primary amines. Five 8-hydroxypenillic ac