69-57-8

Basic information

• Product Name: Penicillin G sodium salt
• Synonyms: benzylpenicillinicacidsodiumsalt;crystapen;mycofarm;novocillin;pen-a-brasive;penicillin-g,monosodiumsalt;penilaryn;Sodium6-(phenylacetamido)-penicillanicacid
• CAS NO: 69-57-8
• Molecular Formula: C₁₆H₁₇N₂O₄S*Na
• Molecular Weight: 356.37
• EINECS: 200-710-2
• Product Categories: Antibiotics for Research and Experimental Use;beta-Lactams (Antibiotics for Research and Experimental Use);Biochemistry;API;PENTIDS;antibiotic;Pharmaceutical raw chemicals
• Mol File: 69-57-8.mol
• Article Data: 0

Chemical Properties

• Melting Point: 209-212°C
• Boiling Point: 663.3 °C at 760 mmHg
• Flash Point: 355 °C
• Appearance: colorless or white/powder
• Density: 1.41
• Vapor Pressure: 1.69E-18mmHg at 25°C
• Refractive Index: 300 ° (C=2, H2O)
• Storage Temp.: 2-8°C
• Solubility: H2O: 100 mg/mL Solutions should be filter sterilized and st
• Water Solubility: 5-10 g/100 mL at 25 ºC
• Stability: Stability Stable, but incompatible with a wide variety of materials, including acids, oxidizing agents, heavy metals, alcohols,
• Merck: 14,7094
• BRN: 3834217
• CAS DataBase Reference: Penicillin G sodium salt(CAS DataBase Reference)
• NIST Chemistry Reference: Penicillin G sodium salt(69-57-8)
• EPA Substance Registry System: Penicillin G sodium salt(69-57-8)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 42/43
• Safety Statements: 22-36/37-45
• WGK Germany: 2
• RTECS: XH9800000
• F: 10-23
• Hazardous Substances Data: 69-57-8(Hazardous Substances Data)

Usage

Chemical Properties

White powder

History

Penicillin was discovered by chance in 1928 by Alexander Fleming. He observed that the growth of a bacteria culture was inhibited by a fungus Penicillum notatum. He published his results but did not pursue its industrial development actively. Ten years later, H. Florey and coworkers had produced enough purified penicillin to treat just one patient. This test, however, was sufficient to prove that it was a viable drug. From then on many people and companies participated in the development of new fermentation technologies, new microorganisms, new downstream processing, and so on to make a large-scale production possible. Penicillin did not only change the medical world, but also the fermentation technology. The naturally growing (wild type) Penicillum notatum produced penicillin with a yield of 10 mg/L. Therefore, the first task was the search for a more productive species. Eventually, Penicillium chrysogenum was identified as the most productive species. To enhance penicillin production further, the old method of growing Penicillum mold on the surface of the medium in liter-sized flasks was replaced by fermentation in large aerated tanks. This allowed the mold to grow throughout the entire tank and not just on the surface of the medium. Today, penicillin and other antibiotics are produced in large-scale fermenters holding several hundred cubic meters of medium and the yield has increased 5000 fold to 50 g/L.

Uses

Different sources of media describe the Uses of 69-57-8 differently. You can refer to the following data:
1. Penicillin G sodium salt is used as a β-lactam antibiotic. Penicillin G can be used as a selective agent in several types of isolation media. It has been used to study the diagnostic and therapeutic implications of gentamicin-resistant Enterococcus faecalis sequence type 6 with reduced penicillin susceptibility and in cell culture both alone and combined with streptomycin and other antibiotics.
2. Penicillin G is a narrow spectrum natural antibiotic. It is effective against Streptococcus pneumoniae, groups A, B, C and G streptococci, nonenterococcal group D streptococci, viridans group streptococci, and non-penicillinase producing staphylococcus. It has been used to study the diagnostic and therapeutic implications of gentamicin-resistant Enterococcus faecalis sequence type 6 with reduced penicillin susceptibility and in cell culture both alone and combined with streptomycin and other antibiotics.
3. Sodium salt of Penicillin G, an antibacterial, antimicrobial medication. Used in the treatment of pneumococcus and streptococcus bacterial infections.

Definition

penicillin: An antibiotic derivedfrom the mould Penicillium notatum;specifically it is known as penicillin Gand belongs to a class of similar substancescalled penicillins. They producetheir effects by disruptingsynthesis of the bacterial cell wall,and are used to treat a variety of infectionscaused by bacteria.

Brand name

Bicillin all purpose;Ceilipen;Cidan-cilina;Cilipen;Coliriocilina;Crisocilin-g;Crystamycin;Crystapen g;Demosa casi penicilina;Dermosa cusipenicilina;Falaper;Gonoper;Hormocillin forte;Ilcocillin;Juvanesta;Lasacilina;Liademycin;M-cillin b;Monocillin;Natricilin;P.g.a.;Paclia g;Patosica;Penibiot;Penicilina klari;Penilevel;Penimiluy;Peniroger;Penitasa "450" simple;Sancilin;Saniciline;Servipan;Sk-penicillin g;Sodiopen;Sodipen;Tabillin;Therapen-na;Triplopen;Unicilina sodia.

World Health Organization (WHO)

Different sources of media describe the World Health Organization (WHO) of 69-57-8 differently. You can refer to the following data:
1. Penicillin is listed separately in the WHO Model List of Essential Drugs.
2. WHO Comment(Benzylpenicillin sodium topical preparations): Benzylpenicillin sodium, one of the first penicillin derivatives to be used in medicine, was introduced in the early 1940s. Topical preparations intended for use on the skin have been associated with allergic rashes and are in general no longer acceptable. However, topical preparations for specialized use, in particular in the eye and on open wounds, are available in many countries. Injectable preparations of benzylpenicillin are included in the WHO Model List of Essential Drugs.

General Description

White to slightly yellow crystalline powder with a faint odor. pH (10% solution) 5.5-7.5.

Air & Water Reactions

Water soluble.

Reactivity Profile

Penicillin G sodium salt is hygroscopic. Penicillin G sodium 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 G sodium 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 G sodium salt may also be incompatible with naphthalene oils and vitamin B.

Fire Hazard

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

Safety Profile

Poison by intracerebral,parenteral, and intramuscular routes. Moderately toxic viaintravenous route. Mildly toxic by ingestion. Experimentalteratogenic and reproductive effects. Questionablecarcinogen with experimental tumorigenic data. Whenheated to

Synthesis

Penicillin can be made by many types of Penicillium fungi, and also by a few types of Asperigillus fungi. In industrial conditions, culture fluids are made that contain more than 30 mg/mL of penicillin. About two-thirds of the produced penicillin is used for making 6-APA. Despite the possibility of pure chemical deacylation, the most prospective way of making 6-APA is an enzymatic method of hydrolyzing benzylpenicillin molecules using immobilized penicyllinamidase, an enzyme isolated from practically all penicillin-producing fungi.

Purification Methods

Purify the salt by dissolving it in a small volume of MeOH (in which it is more soluble than EtOH) and treating gradually with ~5 volumes of EtOAc. This gives an almost colourless crystalline solid (rosettes of clear-cut needles) and recrystallising twice more if slightly yellow in colour. The salt has also been conveniently recrystallised from the minimum volume of 90% Me2CO and adding an excess of absolute Me2CO. A similar procedure can be used with wet n-BuOH. If yellow in colour, then dissolve (~3.8g) in the minimum volume of H2O (3mL), add n-BuOH and filter through a bed of charcoal. The salt forms long white needles on standing in a refrigerator overnight. More crystals can be obtained on concentrating the mother liquors in vacuo at 40o. A further recrystallisation (without charcoal) yields practically pure salt. A good preparation has ~600 Units/mg. The presence of H2O in the solvents increases the solubility considerably. The solubility in mg/100mL at 0o is 6.0 (Me2CO), 15.0 (Me2CO/0.5% H2O), 31.0 (Me2CO/1.0% H2O), 2.4 (methyl ethyl ketone), 81.0 (n-butanol) and 15.0 (dioxane at 14o). Alternatively it is dissolved in H2O (solubility is ~10%), filtered if necessary and precipitated by addition of EtOH and dried in a vacuum over P2O5. A sample can be kept for 24hours at 100o without loss of physiological activity. It also crystallises from MeOH/EtOAc. [IR: Barnes et al. Anal Chem 19 620 1947, The Chemistry of Penicillin (Clarke, Johnson and Robinson eds.) Princeton University Press, Princeton NJ, Chapter V 85 1949, Beilstein 27 III/IV 5861.]

InChI:InChI=1/C16H18N2O4S.Na/c1-16(2)12(15(21)22)18-13(20)11(14(18)23-16)17-10(19)8-9-6-4-3-5-7-9;/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22);/q;+1/p-1

Synthetic route

Penicillin G sodium (69-57-8) + Trimethylenediamine (109-76-2) → C19H28N4O4S

Conditions	Yield
With sodium carbonate In water at 0 - 20℃; for 3h; pH=4; Inert atmosphere;	97%

Penicillin G sodium (69-57-8) + methyl iodide (74-88-4) → penicillin G methyl ester (653-89-4)

Conditions	Yield
In N,N-dimethyl-formamide at 26℃;	92%
In dimethyl sulfoxide for 4h; Ambient temperature;

N-chloromethyl-N-methylbenzamide (51164-42-2) + Penicillin G sodium (69-57-8) → (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid (benzoyl-methyl-amino)-methyl ester (158877-60-2)

Conditions	Yield
In tetrahydrofuran Ambient temperature;	89%

α-bromo-4,5-dimethoxy-2-nitrophenylacetic acid allyl ester (1233875-87-0) + Penicillin G sodium (69-57-8) → penicillin G α-allyloxycarbonyl-4,5-dimethoxy-2-nitrobenzyl ester (1233876-01-1)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	84%

6-nitroveratrylbromide (53413-67-5) + Penicillin G sodium (69-57-8) → 2-nitro-4,5-dimethoxy-benzyl-6-β-(2-phenylacetamido)penicillinate (1415712-97-8)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 17h;	81%

Chloromethyl pivalate (18997-19-8) + Penicillin G sodium (69-57-8) → (pivaloyloxy)methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate (25031-07-6)

Conditions	Yield
In N,N-dimethyl-formamide for 24h; Ambient temperature;	80%

Penicillin G sodium (69-57-8) + p-Methoxybenzyl bromide (2746-25-0) → benzylpenicillin 4-methoxybenzyl ester (30200-14-7)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;	80%

1-(chloromethyl)pyrrolidin-2-one (31282-95-8) + Penicillin G sodium (69-57-8) → (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 2-oxo-pyrrolidin-1-ylmethyl ester (62351-29-5)

Conditions	Yield
In tetrahydrofuran Ambient temperature;	79%

heptane-1,7-diamine (646-19-5) + Penicillin G sodium (69-57-8) → C23H36N4O4S

Conditions	Yield
With sodium carbonate In water at 0 - 20℃; for 3h; pH=4; Inert atmosphere;	77%

methanol (67-56-1) + Penicillin G sodium (69-57-8) + silver nitrate → C34H42Ag2N4O10S2

Conditions	Yield
In water for 0.0833333h;	67%

1,5-diaminopentane (462-94-2) + Penicillin G sodium (69-57-8) → C21H32N4O4S

Conditions	Yield
With sodium carbonate In water at 0 - 20℃; for 3h; pH=4; Inert atmosphere;	61%

N-methyl-N-chloromethylacetamide (4270-65-9) + Penicillin G sodium (69-57-8) → (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid (acetyl-methyl-amino)-methyl ester (51164-31-9)

Conditions	Yield
In tetrahydrofuran Ambient temperature;	56%

diazomethane (186581-53-3, 908094-01-9) + Penicillin G sodium (69-57-8) → penicillin G methyl ester (653-89-4)

Conditions	Yield
With perchloric acid In diethyl ether	50%

Penicillin G sodium (69-57-8) + 4-Chloro-N-chloromethyl-N-methyl-benzamide (144175-29-1) → (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid [(4-chloro-benzoyl)-methyl-amino]-methyl ester (158877-61-3)

Conditions	Yield
In tetrahydrofuran Ambient temperature;	50%

Penicillin G sodium (69-57-8) + Propargylamine (2450-71-7) → (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-N-(prop-2-yn-1-yl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxamide

Conditions	Yield
Stage #1: Penicillin G sodium With hydrogenchloride In water Stage #2: With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.0333333h; Stage #3: Propargylamine Further stages;	38%

mercury(II) diacetate (1600-27-7) + Penicillin G sodium (69-57-8) + acetic acid (64-19-7) → (2S,3S)-1-(2-methylprop-1-en-1-yl)-4-oxo-3-(2-phenylacetamido)azetidin-2-yl acetate (39650-23-2)

Conditions	Yield
at 70℃;	23%

syn-benzaldehyde oxime (932-90-1, 622-31-1, 140461-24-1, 140461-25-2, 622-32-2) + Penicillin G sodium (69-57-8) → N-benzylidene-O-[6β-(2-phenyl-acetylamino)-penicillanoyl]-hydroxylamine (17947-12-5)

Conditions	Yield
(i) ClCO2Et, Py, acetone, (ii) /BRN= 1209596/; Multistep reaction;

4-amino-3,5-diiodo-benzoic acid 2-diethylamino-ethyl ester (717813-39-3) + Penicillin G sodium (69-57-8) → 6β-(2-phenyl-acetylamino)-penicillanic acid; 4-amino-3,5-diiodo-benzoic acid 2-diethylamino-ethyl ester salt (1:1)

Conditions	Yield
In water

4-benzoylamino-benzoic acid 2-diethylamino-ethyl ester (70204-58-9) + Penicillin G sodium (69-57-8) → 6β-(2-phenyl-acetylamino)-penicillanic acid; 4-benzoylamino-benzoic acid 2-diethylamino-ethyl ester salt

Conditions	Yield
In water

4-amino-3,5-dibromo-benzoic acid 2-diethylamino-ethyl ester (129083-47-2) + Penicillin G sodium (69-57-8) → 6β-(2-phenyl-acetylamino)-penicillanic acid; 4-amino-3,5-dibromo-benzoic acid 2-diethylamino-ethyl ester salt (1:1)

Conditions	Yield
In water

4-(4-nitro-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (861531-56-8) + Penicillin G sodium (69-57-8) → 6β-(2-phenyl-acetylamino)-penicillanic acid; 4-(4-nitro-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester salt

Conditions	Yield
In water

Penicillin G sodium (69-57-8) + N-p-tosyl-procaine → 6β-(2-phenyl-acetylamino)-penicillanic acid; 4-(toluene-4-sulfonylamino)-benzoic acid 2-diethylamino-ethyl ester salt

Conditions	Yield
In water

Penicillin G sodium (69-57-8) → penicillin G 1-oxide (34104-15-9)

Conditions	Yield
With sodium periodate In water

Penicillin G sodium (69-57-8) + tert-butylamine (75-64-9) → 6β-(2-phenyl-acetylamino)-penicillanic acid tert-butylamide (34104-21-7)

Conditions	Yield
(i) Et3N, ClCO2Et, CHCl3, (ii) /BRN= 605267/; Multistep reaction;

Penicillin G sodium (69-57-8) + furan-2-carbaldehyde oxime (620-03-1) → N-furfurylidene-O-[6β-(2-phenyl-acetylamino)-penicillanoyl]-hydroxylamine (17947-15-8)

Conditions	Yield
(i) ClCO2Et, Py, acetone, (ii) /BRN= 80664/; Multistep reaction;

propylamine (107-10-8) + Penicillin G sodium (69-57-8) → benzylpenicilloic acid (13057-98-2, 87492-68-0, 89014-19-7, 96572-86-0, 96572-87-1) + (2R,4S)-5,5-Dimethyl-2-(phenylacetylamino-propylcarbamoyl-methyl)-thiazolidine-4-carboxylic acid (27826-46-6, 47550-94-7)

Conditions	Yield
In water at 30℃; Mechanism; Rate constant; ionic strength: 0.25 M (KCl), k1, k22, k3;

2-cyanoethylamine (151-18-8) + Penicillin G sodium (69-57-8) → benzylpenicilloic acid (13057-98-2, 87492-68-0, 89014-19-7, 96572-86-0, 96572-87-1) + (2R,4S)-2-[(2-Cyano-ethylcarbamoyl)-phenylacetylamino-methyl]-5,5-dimethyl-thiazolidine-4-carboxylic acid

Conditions	Yield
In water at 30℃; Mechanism; Rate constant; ionic strength: 0.25 M (KCl), k1, k22, k3;

trifluoroethylamine (753-90-2) + Penicillin G sodium (69-57-8) → benzylpenicilloic acid (13057-98-2, 87492-68-0, 89014-19-7, 96572-86-0, 96572-87-1) + (2R,4S)-5,5-Dimethyl-2-[phenylacetylamino-(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-thiazolidine-4-carboxylic acid

Conditions	Yield
In water at 30℃; Mechanism; Rate constant; ionic strength: 0.25 M (KCl), k1, k22, k3;

Tau (107-35-7) + Penicillin G sodium (69-57-8) → benzylpenicilloic acid (13057-98-2, 87492-68-0, 89014-19-7, 96572-86-0, 96572-87-1) + (2R,4S)-5,5-Dimethyl-2-[phenylacetylamino-(2-sulfo-ethylcarbamoyl)-methyl]-thiazolidine-4-carboxylic acid

Conditions	Yield
In water at 30℃; Mechanism; Rate constant; ionic strength: 0.25 M (KCl), k1, k22, k3;

Penicillin G sodium (69-57-8) + 2-ammonioethylamine (26265-69-0) → benzylpenicilloic acid (13057-98-2, 87492-68-0, 89014-19-7, 96572-86-0, 96572-87-1) + (2R,4S)-2-[(2-Amino-ethylcarbamoyl)-phenylacetylamino-methyl]-5,5-dimethyl-thiazolidine-4-carboxylic acid

Conditions	Yield
In water at 30℃; Mechanism; Rate constant; ionic strength: 0.25 M (KCl), k1, k22, k3;

Downstream Products

• 17947-12-5 N-benzylidene-O-[6β-(2-phenyl-acetylamino)-penicillanoyl]-hydroxylamine 
• 34104-21-7 6β-(2-phenyl-acetylamino)-penicillanic acid tert-butylamide 
• 17947-15-8 N-furfurylidene-O-[6β-(2-phenyl-acetylamino)-penicillanoyl]-hydroxylamine 
• 13057-98-2 benzylpenicilloic acid 
• 27826-46-6 (2R,4S)-5,5-Dimethyl-2-(phenylacetylamino-propylcarbamoyl-methyl)-thiazolidine-4-carboxylic acid 
• 25031-07-6 (pivaloyloxy)methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 
• 54275-92-2 6-β-phenylacetamidopenicillanic acid-(1S)-oxide 
• 62351-29-5 (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 2-oxo-pyrrolidin-1-ylmethyl ester 
• 51164-31-9 (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid (acetyl-methyl-amino)-methyl ester 
• 158877-61-3 (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid [(4-chloro-benzoyl)-methyl-amino]-methyl ester 
• 643-43-6 (2,4-dinitro-phenyl)-acetic acid 
• 67099-38-1 o-Nitrophenaceturaldehyd 
• 34104-31-9 3-methyl-2-[3-oxo-4-(2-phenyl-acetylamino)-3H-isothiazol-2-yl]-but-3-enoic acid tert-butylamide 
• 34104-26-2 3-methyl-2-[3-oxo-4-(2-phenyl-acetylamino)-3H-isothiazol-2-yl]-but-3-enoic acid 4-nitro-benzyl ester