7704-67-8

Basic information

• Product Name: Erythromycin thiocyanate
• Synonyms: ERYTHROMYCIN THIOCYANATE;ERYTHROMYCIN THIOCYNATE;ERYTHROMYCIN THIOCYANATE NOT LESS THAN 750 U OF ERYFHROMYCIN PER MG;ERYTHROMYCIN THIOCYANATE CP2000;Erythromycin, thiocyanate (salt);ErythroMycin Thiocyanate CGMP;ErythroMicyn thiocyanate;ERTHROMYCIN THIOCYANATE
• CAS NO: 7704-67-8
• Molecular Formula: CHNS*C₃₇H₆₇NO₁₃
• Molecular Weight: 793.02
• EINECS: 231-723-1
• Product Categories: Veterinaries;API;Antibiotic medicines
• Mol File: 7704-67-8.mol
• Article Data: 3

Chemical Properties

• Melting Point: 166-167 °C
• Boiling Point: 818.4 °C at 760 mmHg
• Flash Point: 448.8 °C
• Appearance: /
• Vapor Pressure: 4.94E-31mmHg at 25°C
• CAS DataBase Reference: Erythromycin thiocyanate(CAS DataBase Reference)
• NIST Chemistry Reference: Erythromycin thiocyanate(7704-67-8)
• EPA Substance Registry System: Erythromycin thiocyanate(7704-67-8)

Safety Data

• Hazardous Substances Data: 7704-67-8(Hazardous Substances Data)

Usage

Macrolide antibiotics

Thiocyanate thiocyanate is the thiocyanate of commonly used macrolide antibiotic erythromycin. It is a veterinary product for the treatment of gram-positive bacteria and mycoplasma infections, and has been widely used as an "animal growth promoters" in a foreign country. In China together with tylosin, tetracycline and oxytetracycline, they are the largest exported veterinary antibiotics products. In addition the product is used as an important intermediate in the synthesis of mainstream macrolide antibiotics product, for example erythromycin, roxithromycin, azithromycin and clarithromycin. China began the production of erythromycin thiocyanate in 1980s-1990s, but the yield was less than 100 tons. By 2007 it became the largest exported macrolide antibiotic with production capacity more than 10,000 tons. The antibacterial spectrum of erythromycin thiocyanate is similar to that of benzylpenicillin. It has strong effect to staphylococcus aureus, streptococcus and pneumoniae bacteria in gram-positive bacteria, and also has some effect to pasteurella and brucella in gram-negative bacteria. In addition to that, the product is effective to mycoplasma, rickettsia, leptospira, actinomycetes and ardia, but non-effective to echerichia coli, salmonella spp and other intestinal negative bacteria. It is mainly used for serious infections caused by drug-resistant Staphylococcus aureus and hemolytic streptococcus, such as pneumonia, septicemia, endometritis and mastitis etc. Besides it also has good effect on mycoplasma-caused chronic respiratory disease in poultry and swine mycoplasma pneumonia. Moreover it is also used for nocardiosis treatment of dogs and cats, for prevention of white head and mouth disease of black, grass, bighead carp and other fish species, bacterial gill disease of grass and black carp, white fish disease of silver, bighead carp and other fish, and streptococcus disease of tilapia.

Uses

Different sources of media describe the Uses of 7704-67-8 differently. You can refer to the following data:
1. Antibiotic medicines, For the treatment Infections caused by penicillin-resistant staphylococcus and streptococcus etc.
2. Food additive; drug (veterinary).

Chemical Properties

White or almost white powder.

InChI:InChI=1/C37H67NO13.CHNS/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26;2-1-3/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3;3H/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-;/m1./s1

Synthetic route

sodium thiocyanide (540-72-7) + erythromycin (114-07-8) → erythromycin A thiocyanate (7704-67-8)

Conditions	Yield
Stage #1: erythromycin In acetone at 35℃; pH=8.5; Stage #2: sodium thiocyanide In acetone Concentration; pH-value; Temperature; Solvent;	85.1%
Stage #1: erythromycin With LACTIC ACID; water at 5 - 40℃; Stage #2: sodium thiocyanide In water at -15 - 10℃; Product distribution / selectivity;
Stage #1: erythromycin In acetone at 35℃; pH=8.5; Stage #2: sodium thiocyanide In acetone	85.1 %Chromat.

ammonium thiocyanate + erythromycin lactate → erythromycin A thiocyanate (7704-67-8)

Conditions	Yield
Stage #1: erythromycin lactate In acetone at 40℃; pH=9; Stage #2: ammonium thiocyanate In acetone pH-value;	84.9%

ammonium thiocyanate + erythromycin lactate → erythromycin A thiocyanate (7704-67-8)

Conditions	Yield
Stage #1: erythromycin lactate In acetone at 40℃; pH=9.0; Stage #2: ammonium thiocyanate In acetone at 45℃; pH-value; Reagent/catalyst;	84.9 %Chromat.

erythromycin A thiocyanate (7704-67-8) → erythromycin (114-07-8)

Conditions	Yield
With sodium hydroxide In methanol at 40℃; pH=9-9.8;	99.33%
With ammonia In dichloromethane; water at 25 - 35℃;
In dichloromethane; water at 37℃; pH=12; Product distribution / selectivity;
With ammonia In water at 35 - 70℃; for 1.5h; Reagent/catalyst;	106 g

erythromycin A thiocyanate (7704-67-8) → erythromycin A oxime thiocyanate (1357466-70-6)

Conditions	Yield
Stage #1: erythromycin thiocyanate A With hydroxylamine hydrochloride In ethanol at 20℃; for 0.5h; Large scale; Stage #2: With pyridine In ethanol at 20℃; for 3h; Reflux; Large scale;	95%
With hydroxylamine hydrochloride; triethylamine In methanol at 30 - 55℃; for 52h; pH=6.3 - 6.7;

erythromycin A thiocyanate (7704-67-8) → erythromycin-hydrazone (36416-30-5)

Conditions	Yield
With hydrazine hydrate In methanol at 60 - 70℃; for 12h; Temperature; Solvent;	94.3%

erythromycin A thiocyanate (7704-67-8) → C37H66N2O12

Conditions	Yield
Stage #1: erythromycin thiocyanate A With ammonia In dichloromethane; water at 25℃; Stage #2: With hydroxylamine hydrochloride; triethylamine In methanol at 20 - 55℃; for 25.1667h; Heating / reflux; Stage #3: With sodium hydroxide; ammonia; sodium hydrogencarbonate; acetic acid; p-toluenesulfonyl chloride more than 3 stages;	90%

erythromycin A thiocyanate (7704-67-8) + caprylohydroxamic acid (7377-03-9) → 9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza-homoerythromycin A (342371-84-0)

Conditions	Yield
Stage #1: erythromycin thiocyanate A; caprylohydroxamic acid In acetonitrile at 20℃; for 0.166667h; Stage #2: With sulfuric acid In dimethyl sulfoxide; acetone at 80℃; for 16h; Concentration; Temperature; Reagent/catalyst; Solvent;	90%

erythromycin A thiocyanate (7704-67-8) → erythromycin A oxime thiocyanate

Conditions	Yield
With hydroxylamine hydrochloride; ammonium bicarbonate In methanol at -10 - 80℃; pH=6 - 7;

erythromycin A thiocyanate (7704-67-8) → (9-E)-deoxo-9-hydroximinoerythromycin A (13127-18-9)

Conditions	Yield
With hydroxylamine hydrochloride In dichloromethane at 20℃; for 1.5h; pH=7; Beckmann Rearrangement;
With hydroxylamine hydrochloride; ammonium bicarbonate; sodium iodide In methanol at 56 - 60℃; Reagent/catalyst;	89 g

erythromycin A thiocyanate (7704-67-8) → 9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza-homoerythromycin A (342371-84-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride / dichloromethane / 1.5 h / 20 °C / pH 7 2: sodium hydrogencarbonate; p-toluenesulfonyl chloride / dichloromethane / 1.5 h / 20 °C View Scheme

erythromycin A thiocyanate (7704-67-8) → C37H70N2O12

Conditions	Yield
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride / dichloromethane / 1.5 h / 20 °C / pH 7 2: sodium hydrogencarbonate; p-toluenesulfonyl chloride / dichloromethane / 1.5 h / 20 °C 3: potassium borohydride / dichloromethane; chloroform / 4.5 h / 20 °C View Scheme

erythromycin A thiocyanate (7704-67-8) → Zithromax(R) (83905-01-5, 92470-27-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydroxylamine hydrochloride / dichloromethane / 1.5 h / 20 °C / pH 7 2: sodium hydrogencarbonate; p-toluenesulfonyl chloride / dichloromethane / 1.5 h / 20 °C 3: potassium borohydride / dichloromethane; chloroform / 4.5 h / 20 °C 4: formic acid / chloroform / 9 h / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: hydroxylamine hydrochloride; triethylamine / methanol / 52 h / 30 - 55 °C / pH 6.3 - 6.7 2.1: sodium hydrogencarbonate; p-toluenesulfonyl chloride / acetone / 4 h / 0 - 10 °C 3.1: phosphoric acid; potassium borohydride / water / 8 h / 0 - 5 °C / pH 7 - 9 3.2: 3 h / 0 - 5 °C / pH 2.5 - 3 4.1: formic acid / acetone / 4 h / 30 - 55 °C View Scheme

erythromycin A thiocyanate (7704-67-8) → C37H68N2O13*CHNS

Conditions	Yield
With hydroxylamine hydrochloride; acetic acid; triethylamine In methanol; water at 55℃; for 24h; pH=6.5 - 6.9; pH-value;	133.6 g

erythromycin A thiocyanate (7704-67-8) → erythromycin A 6,9-imino ether

Conditions	Yield
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; triethylamine / methanol / 52 h / 30 - 55 °C / pH 6.3 - 6.7 2: sodium hydrogencarbonate; p-toluenesulfonyl chloride / acetone / 4 h / 0 - 10 °C View Scheme

erythromycin A thiocyanate (7704-67-8) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydroxylamine hydrochloride; triethylamine / methanol / 52 h / 30 - 55 °C / pH 6.3 - 6.7 2.1: sodium hydrogencarbonate; p-toluenesulfonyl chloride / acetone / 4 h / 0 - 10 °C 3.1: phosphoric acid; potassium borohydride / water / 8 h / 0 - 5 °C / pH 7 - 9 3.2: 3 h / 0 - 5 °C / pH 2.5 - 3 View Scheme

Upstream product

• 540-72-7 sodium thiocyanide 
• 114-07-8 erythromycin 

Downstream Products

• 114-07-8 erythromycin 
• 76801-85-9 9-Deoxo-9a-aza-9a-homoerythromycin A 
• 342371-84-0 9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza-homoerythromycin A 
• 83905-01-5 Zithromax(R) 
• 13127-18-9 (9-E)-deoxo-9-hydroximinoerythromycin A 

Relevant articles and documents

PREPARATION PROCESS OF ERYTHROMYCIN THIOCYANATE

Disclosed is a preparation process of erythromycin thiocyanate, which belongs to the pharmaceutical field. The preparation process provided by the invention uses erythromycin or its salt(s) as raw material(s), dissolves it/them in acetone or the mixed solvent containing acetone and obtains erythromycin thiocyanate rich in erythromycin thiocyanate A as the main component and low in the content of impurities. Said erythromycin thiocyanate could be used as the raw material for preparing Azithromycin and Clarithromycin, which meets to the standards made by European Union and US.

HYDRATES OF ERYTHROMYCIN SALTS, THE PREPARATION AND THE USE THEREOF

The present invention relates to a macrolide derivative as well as preparation and use thereof. The macrolide derivative of the present invention, i.e., a hydrate of erythromycin salts, has a molecular formula of C37H67NO13·A·nH2O, n=1.0-11.0, in which A is an organic acid or an organic acids, selected from lactobionic acid, thiocyanic acid, maleic acid, fumaric acid, thiocyanic acid, acetic acid, methanesulfonic acid, benzenesulfonic acid, nicotinic acid, lactic acid, citric acid, tartaric acid, aspartic acid, glutamic acid and phosphoric acid, the hydrate has good water solubility and better storage stability, which is suitable for the manufacture of a medicament for the treatment and prophylaxis of infectious diseases in human or animal caused by Gram-positive or negative bacteria.