69388-84-7

Basic information

• Product Name: Sulbactam sodium
• Synonyms: SULBACTAM SODIUM;SULBACTAM SODIUM SALT;sodium (2s-cis)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 4,4-dioxide;SODIUM SULBACTAM;4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylicacid,3,3-dimethyl-7-oxo-,4,4-d;cp45899sodiumsalt;penicillanicacid1,1-dioxidesodiumsalt;penicillanicaciddioxidesodiumsalt
• CAS NO: 69388-84-7
• Molecular Formula: C₈H₁₀NO₅S*Na
• Molecular Weight: 255.22
• EINECS: 273-984-4
• Product Categories: Pharma;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Antibiotic;Pharmaceutical raw materials;Inhibitors;pharmaceutical raw material
• Mol File: 69388-84-7.mol
• Article Data: 7

Chemical Properties

• Melting Point: >230°C (dec.)
• Boiling Point: 567.7oC at 760 mmHg
• Flash Point: 297.1oC
• Appearance: COA
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Freely soluble in water, sparingly soluble in ethyl acetate, very slightly soluble in ethanol (96 per cent). It is freely soluble in dilute acids.
• CAS DataBase Reference: Sulbactam sodium(CAS DataBase Reference)
• NIST Chemistry Reference: Sulbactam sodium(69388-84-7)
• EPA Substance Registry System: Sulbactam sodium(69388-84-7)

Safety Data

• Hazard Codes: Xn
• Statements: 42/43
• Safety Statements: 22-24-36/37-45-24/25
• Hazardous Substances Data: 69388-84-7(Hazardous Substances Data)

Usage

Description

Sulbactam sodium, also known as SULPERAZONE, is a parenterally-active, semi-synthetic β-lactamase inhibitor. It is a white solid that has been introduced as a 1:1 combination product with cefoperazone. Sulbactam sodium enhances the effectiveness of β-lactam antibiotics against resistant strains, similar to clavulanic acid, the first agent of this type to be introduced.

Uses

Used in Pharmaceutical Industry:
Sulbactam sodium is used as a β-lactamase inhibitor for enhancing the effectiveness of β-lactam antibiotics against resistant strains. It is particularly useful in combination with cefoperazone, providing a more potent antibacterial effect against various bacterial infections.
Used in Antimicrobial Applications:
Sulbactam sodium is employed as an antimicrobial agent, working synergistically with β-lactam antibiotics to combat resistant bacterial strains. This combination therapy helps to overcome the challenges posed by antibiotic resistance and improves the overall efficacy of treatment.

Safety Profile

Poison by intravenous route. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx and SOx

InChI:InChI=1/C8H11NO5S.Na/c1-8(2)6(7(11)12)9-4(10)3-5(9)15(8,13)14;/h5-6H,3H2,1-2H3,(H,11,12);/q;+1/t5-,6+;/m1./s1

Synthetic route

sulbactum (68373-14-8) → sodium sulbactam (69388-84-7)

Conditions	Yield
With sodium isooctanoate In ethyl acetate	99.3%
With sodium 2-ethylhexanoic acid In water; isopropyl alcohol at 20 - 35℃; for 2.33333h;	95%
With sodium acetate; sodium hydrogencarbonate at 20 - 25℃; pH=5.5 - 6;
With sodium isooctanoate In methanol; water at 25℃; pH=4.5; Reagent/catalyst; Solvent; Temperature; pH-value;	542g

penicillanic acid (87-53-6) → sodium sulbactam (69388-84-7)

Conditions	Yield
Stage #1: penicillanic acid With potassium permanganate; sulfuric acid; acetic acid In water at 5 - 8℃; for 2.5h; Heating; Stage #2: With sodium acetate; pyrographite In ethanol at 40℃; for 1h; Solvent;	95.3%

tetrabis(triphenylphosphine)palladium + Diethyl phosphonate (762-04-9, 123-22-8) + allyl 6,6-dibromopenicillanate 1,1-dioxide (114333-65-2) + sodium 2-ethylhexanoic acid → sodium sulbactam (69388-84-7)

Conditions	Yield
With sodium hydrogencarbonate; triethylamine; triphenylphosphine In water; ethyl acetate	2.22 g (87%)

Diethyl phosphonate (762-04-9, 123-22-8) + 6,6-dibromopenicillanic acid-1,1-dioxide (76646-91-8) → sodium sulbactam (69388-84-7)

Conditions	Yield
With sodium hydrogencarbonate In water; ethyl acetate	9.78 g (76.5%)

6-Aminopenicillanic Acid (551-16-6) → sodium sulbactam (69388-84-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: bromine; sulfuric acid; sodium nitrite / ethyl acetate / 1 h / 5 °C 2.1: potassium permanganate; sodium hydroxide; phosphoric acid / water / 0.5 h / 0 °C / pH 5.7 3.1: zinc / water / 0 °C / pH 1.5 - 5.8 3.2: 1 h View Scheme
Multi-step reaction with 4 steps 1.1: hydrogen bromide; sodium nitrite; sulfuric acid / water / 1.5 h / 0 - 5 °C / pH Ca. 2.5 1.2: 1 h / 0 - 5 °C 2.1: sodium hydroxide; water; potassium permanganate; phosphoric acid / 0 - 5 °C 3.1: zinc / water / 1.5 h / 0 °C / pH Ca. 3.5 4.1: sodium isooctanoate / ethyl acetate View Scheme

6,6-dibromopenicillanic acid-1,1-dioxide (76646-91-8) → sodium sulbactam (69388-84-7)

Conditions	Yield
Stage #1: 6,6-dibromopenicillanic acid-1,1-dioxide With zinc In water at 0℃; pH=1.5 - 5.8; Stage #2: With sodium 2-ethylhexanoic acid In water; acetone for 1h; Temperature;	288.1 g

6,6-dibromopenicillanic acid (24158-88-1) → sodium sulbactam (69388-84-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide; water; potassium permanganate; phosphoric acid / 0 - 5 °C 2: zinc / water / 1.5 h / 0 °C / pH Ca. 3.5 3: sodium isooctanoate / ethyl acetate View Scheme

sodium sulbactam (69388-84-7) → sulbactum (68373-14-8)

Conditions	Yield
With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide In dichloromethane; water at 20℃; for 0.166667h; pH=6.9 - 7;	94.8%
With hydrogenchloride In water; ethyl acetate	87.2%
Multi-step reaction with 2 steps 1: 86 percent / hexamethylphosphoric acid triamide / 18 h / 55 °C 2: 99 percent / sodium p-toluenesulfinate tetrahydrate, Pd(PPh3)4 / methanol; tetrahydrofuran / 1 h / Ambient temperature View Scheme

3-bromo-2-chloroprop-1-ene (4860-96-2) + sodium sulbactam (69388-84-7) → (2S,5R)-3,3-Dimethyl-4,4,7-trioxo-4λ6-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 2-chloro-allyl ester

Conditions	Yield
In N,N,N,N,N,N-hexamethylphosphoric triamide at 55℃; for 18h;	86%

Chloromethyl pivalate (18997-19-8) + sodium sulbactam (69388-84-7) → (pivaloyloxy)methyl 6,6-dihydropenicillanate S,S-dioxide (69388-79-0)

Conditions	Yield
In dimethyl sulfoxide at 20 - 25℃; for 18h; Substitution;	85%
With tetrabutylammomium bromide In acetone for 18h; Heating;

sodium sulbactam (69388-84-7) + benzyl bromide (100-39-0) → (2S,5R)-Benzyl 3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 4,4-Dioxide (69388-78-9)

Conditions	Yield
With N,N-dimethyl-formamide	80%
In N,N-dimethyl-formamide for 12h;	80%

sodium sulbactam (69388-84-7) → Chloromethyl penicillanic acid 1,1-dioxide

Conditions	Yield
With tetra(n-butyl)ammonium hydrogen sulfate In water	80%

phenylthiomethyl chloride (7205-91-6) + sodium sulbactam (69388-84-7) → phenylthiomethyl penicillanate sulfone

Conditions	Yield
With sodium chloride; tetra-(n-butyl)ammonium iodide; sodium hydrogencarbonate In dichloromethane; acetone	74%

chloro-methylsulfanyl-methane (2373-51-5) + sodium sulbactam (69388-84-7) → methylthiomethyl penicillanate sulfone

Conditions	Yield
With sodium chloride; tetra-(n-butyl)ammonium iodide; sodium hydrogencarbonate In dichloromethane; acetone	66%

chloromethyl tert-butyl sulfide (83516-16-9) + sodium sulbactam (69388-84-7) → t-butylthiomethyl penicillanate sulfone

Conditions	Yield
With sodium chloride; tetra-(n-butyl)ammonium iodide; sodium hydrogencarbonate In diethyl ether; dichloromethane; water; acetone	49%

chloromethyl 6-(2-[4-nitrobenzyloxycarbonylamino]-2-[4-hydroxyphenyl]acetamido)penicillanate + ethyl acetate n-hexane + sodium sulbactam (69388-84-7) → 6'-(2-[4-nitrobenzyloxycarbonylamino]-2-[4-hydroxyphenyl]acetamido)penicillanoyloxymethyl penicillanate 1,1-dioxide (103063-56-5)

Conditions	Yield
With sodium iodide In water; dimethyl sulfoxide	18%

3,5-bis[bis-((1-methyl-1H-imidazol-2-yl)-methyl)amine]-1H-pyrazole (938173-57-0) + sodium sulbactam (69388-84-7) + zinc trifluoromethanesulfonate (54010-75-2) + acetonitrile (75-05-8) → [[3,5-bis[bis-((1-methyl-1H-imidazol-2-yl)-methyl)amine]-1H-pyrazole]Zn2(sulbactam)](CF3SO3)2*2CH3CN

Conditions	Yield
With KOtBu In acetonitrile under Ar, Schlenk techniques; pyrazole compd., KOtBu, Zn(CF3SO3)2, and sulbactam salt dried in vac., dry MeCN added, stirred (3 d); slow diffusion of Et2O into MeCN; XRD;	15%

NH-pyrazole (288-13-1) + sodium sulbactam (69388-84-7) → (Z)-1-(5-carboxy-6-methyl-6-sulfono-4-aza-2-heptenoyl)pyrazole + (E)-1-(5-carboxy-6-methyl-6-sulfono-4-aza-2-heptenoyl)pyrazole

Conditions	Yield
at 60℃; for 3h; pH 7.0;

1H-imidazole (288-32-4) + sodium sulbactam (69388-84-7) → 2-((Z)-3-Imidazol-1-yl-3-oxo-propenylamino)-3-methyl-3-sulfino-butyric acid + 2-((E)-3-Imidazol-1-yl-3-oxo-propenylamino)-3-methyl-3-sulfino-butyric acid

Conditions	Yield
at 60℃; for 3h; pH 9.0;

1,2,4-Triazole (288-88-0) + sodium sulbactam (69388-84-7) → 3-Methyl-2-((Z)-3-oxo-3-[1,2,4]triazol-1-yl-propenylamino)-3-sulfino-butyric acid + 3-Methyl-2-((E)-3-oxo-3-[1,2,4]triazol-1-yl-propenylamino)-3-sulfino-butyric acid

Conditions	Yield
at 60℃; for 3h; pH 9.0;

methanol (67-56-1) + sodium sulbactam (69388-84-7) → (Z)-methyl 5-carboxy-6-methyl-6-sulfono-4-aza-2-heptenoate (98380-72-4, 98380-74-6) + (E)-methyl-5-carboxy-6-methyl-6-sulfono-4-aza-2-heptenoate (98380-72-4, 98380-74-6)

Conditions	Yield
at 60℃; for 3h; pH 9.0;

sodium sulbactam (69388-84-7) → 3-oxopropanoic acid (926-61-4) + 2-amino-3-methyl-3-sulfinobutanoic acid (98462-04-5)

Conditions	Yield
With borate buffer at 65℃; for 1.5h;

sodium sulbactam (69388-84-7) → 2-diazoacetyl-3,3-dimethyl-4,4-dioxo-4-thia-1-azabicyclo[3.2.0]heptan-7-one (118733-55-4)

Conditions	Yield
With chloroformic acid ethyl ester; triethylamine hydrochloride 1.) CH2Cl2, (CCl4-solid CO2), 0.5 h, r.t., 0.5 h, 2.) Et2O, 0 deg C, 2 h; Yield given. Multistep reaction;

sodium sulbactam (69388-84-7) → (Z)-methyl 5-carboxy-6-methyl-6-sulfono-4-aza-2-heptenoate (98380-72-4, 98380-74-6) + (E)-methyl-5-carboxy-6-methyl-6-sulfono-4-aza-2-heptenoate (98380-72-4, 98380-74-6)

Conditions	Yield
With sodium hydroxide In methanol for 0.5h; Ambient temperature;

sodium sulbactam (69388-84-7) → (2R,4S)-4-benzyloxycarbonyl-2-methoxycarbonylmethyl-5,5-dimethyl-3-trifluoroacetylthiazolidine 1,1-dioxide (90473-66-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / N,N-dimethylformamide View Scheme

sodium sulbactam (69388-84-7) → (7R)-2-isopropylidene-5-oxa-6-thia-1-azabicyclo<5.2.0>nonane-3,9-dione 6-oxide (118733-56-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) triethylamine hydrochloride, ethyl chloroformate / 1.) CH2Cl2, (CCl4-solid CO2), 0.5 h, r.t., 0.5 h, 2.) Et2O, 0 deg C, 2 h 2: 74 percent / 95percent DBN / CDCl3 View Scheme

chlorobromomethane (74-97-5) + sodium sulbactam (69388-84-7) → Chloromethyl penicillanic acid 1,1-dioxide

Conditions	Yield
With tetra(n-butyl)ammonium hydrogen sulfate; silica gel In water

dichloromethane (75-09-2) + sodium sulbactam (69388-84-7) → tetra-n-butylammonium salt of penicillanic acid 1,1-dioxide

Conditions	Yield
With sodium hydroxide; tetra(n-butyl)ammonium hydrogen sulfate In water

chloromethyl 6-(2-benzyloxycarbonylamino-2-phenylacetamido)penicillanate + sodium sulbactam (69388-84-7) → 6'-(2-Benzyloxycarbonylamino-2-phenylacetamido)-penicillanoyloxymethyl Penicillanate 1,1-Dioxide (84519-07-3)

Conditions	Yield
With sodium iodide; dimethyl sulfoxide In water
With potassium iodide In water; pyrographite; dimethyl sulfoxide

chloromethyl 6-(2-[4-nitrobenzyloxycarbonylamino]-2-phenylacetamido)penicillanate + sodium sulbactam (69388-84-7) → 6'-(2-[4-Nitrobenzyloxycarbonylamino]-2phenylacetamido)penicillanoyloxymethyl penicillanate 1,1-dioxide (103063-55-4)

Conditions	Yield
With sodium iodide; dimethyl sulfoxide

phosgene (75-44-5) + sodium sulbactam (69388-84-7) + recorcinol (108-46-3) → m-Hydroxyphenyl Penicillanate 1,1-Dioxide (84397-03-5)

Conditions	Yield
With pyridine In N-methyl-acetamide; tetrachloromethane; dichloromethane

ethyl acetate n-hexane + sodium sulbactam (69388-84-7) + 4-bromomethyl-1,3-dioxa-5-methylcyclopentene-2-one (80715-22-6) → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl penicillanate 1,1-dioxide (85871-31-4)

Conditions	Yield
With tetrabutylammomium bromide In ethyl acetate; acetone

benzyl 2-(iodomethoxycarbonyl)phenyl acetate + sodium sulbactam (69388-84-7) → 2-(1,1-Dioxopenicillanoyloxymethoxycarbonyl)phenylacetic acid

Conditions	Yield
With dimethyl sulfoxide

chloromethyl cyclohexyl sulphide (68483-71-6) + sodium sulbactam (69388-84-7) → cyclohexylthiomethyl penicillanate sulfone

Conditions	Yield
With sodium chloride; tetra-(n-butyl)ammonium iodide; sodium hydrogencarbonate In dichloromethane; water; acetone

4-nitrobenzyl 6-(2-chloromethoxycarbonylamino-2-phenylacetamido)penicillanate + sodium sulbactam (69388-84-7) → 4-nitrobenzyl 6-(2-[1,1-dioxopenicillanoyloxymethoxycarbonylamino]-2-phenylacetamido)penicillanate

Conditions	Yield
With sodium iodide In ethyl acetate; N,N-dimethyl-formamide

Upstream product

• 24158-88-1 6,6-dibromopenicillanic acid 
• 76646-91-8 6,6-dibromopenicillanic acid-1,1-dioxide 
• 551-16-6 6-Aminopenicillanic Acid 
• 87-53-6 penicillanic acid 
• 68373-14-8 sulbactum 
• 762-04-9 Diethyl phosphonate 
• 114333-65-2 allyl 6,6-dibromopenicillanate 1,1-dioxide 

Downstream Products

• 76247-39-7 iodomethyl penicillanate 1,1-dioxide 
• 76247-40-0 chloromethyl penicillanate 1,1-dioxide 
• 83031-45-2 dibenzylamine salt of penicillanic acid 1,1-dioxide 
• 84397-03-5 m-Hydroxyphenyl Penicillanate 1,1-Dioxide 
• 103063-55-4 6'-(2-[4-Nitrobenzyloxycarbonylamino]-2phenylacetamido)penicillanoyloxymethyl penicillanate 1,1-dioxide 
• 84519-07-3 6'-(2-Benzyloxycarbonylamino-2-phenylacetamido)-penicillanoyloxymethyl Penicillanate 1,1-Dioxide 
• 103063-56-5 6'-(2-[4-nitrobenzyloxycarbonylamino]-2-[4-hydroxyphenyl]acetamido)penicillanoyloxymethyl penicillanate 1,1-dioxide 
• 90473-66-8 (2R,4S)-4-benzyloxycarbonyl-2-methoxycarbonylmethyl-5,5-dimethyl-3-trifluoroacetylthiazolidine 1,1-dioxide 
• 68373-14-8 sulbactum 
• 69388-78-9 (2S,5R)-Benzyl 3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 4,4-Dioxide 
• 926-61-4 3-oxopropanoic acid 
• 98462-04-5 2-amino-3-methyl-3-sulfinobutanoic acid 
• 69388-79-0 (pivaloyloxy)methyl 6,6-dihydropenicillanate S,S-dioxide 

Relevant articles and documents

New indications of troxofine ceftriaxone sodium pharmaceutical preparation for treatment of infection of patients with immunodeficiency

The invention belongs to the technical field of drug preparation, and discloses new indications of a troxofine ceftriaxone sodium pharmaceutical preparation for treatment of infection of patients withimmunodeficiency. By improving a raw material synthesis process, ceftriaxone sodium with the high effective constituent content and the low impurity content is provided so as to solve the problems ofpoor stability and reducing of the antibacterial effect of a ceftriaxone sodium preparation due to impurities. The ceftriaxone sodium provided by the specific production process is very low in impurity content and significant in efficacy, the quality of a preparation product is improved advantageously, safety and effectiveness of the preparation product are ensured, and the preparation product has uses in the aspects of preparing drugs for treating infection of the patients with immunodeficiency.

Sulbactam sodium preparation method

The invention relates to a sulbactam sodium preparation method belongs to the technical field of synthesis of beta-lactamase inhibitors. The sulbactam sodium preparation method comprises the steps that 6-amino penicillanic acid (6-APA) is used as a raw material, reacts in strong acid and a sodium nitrite water solution, then reacts under the effects of copper powder and hypophosphorous acid, and then a target product sulbactam sodium is prepared through oxidation and substitution reaction. The reaction process is simple in operation, the method includes few reaction steps, a by-product is reduced, the final reaction yield is high, the treatment difficulty and cost after wastewater production are reduced, the pressure of environmental protection is reduced for enterprises, the product production cost is reduced, and the sulbactam sodium preparation method is suitable for industrial production.

Ampicillin sodium and sulbactam sodium pharmaceutical composition

The present invention discloses an ampicillin sodium and sulbactam sodium pharmaceutical composition comprising sulbactam sodium and ampicillin sodium with the specific optical rotation of + 264 degrees to + 269 degrees, and the mass ratio of ampicillin sodium to sulbactam sodium is 2: 1. The ampicillin sodium and sulbactam sodium pharmaceutical composition is prepared from the sulbactam sodium and the ampicillin sodium with the particular specific optical rotation, the drug stability is improved, and drug safety is improved.