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Clarithromycin

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Name

Clarithromycin

EINECS 1806241-263-5
CAS No. 81103-11-9 Density 1.184 g/cm3
PSA 182.91000 LogP 2.43970
Solubility 99.48mg/L(20 oC) Melting Point 217-220 °C
Formula C38H69NO13 Boiling Point 805.478 °C at 760 mmHg
Molecular Weight 747.965 Flash Point 440.937 °C
Transport Information N/A Appearance Colourless crystalline needles
Safety 26-36 Risk Codes 22-36/37/38
Molecular Structure Molecular Structure of 81103-11-9 (Clarithromycin) Hazard Symbols HarmfulXn, IrritantXi
Synonyms

Adel;Mabicrol;TE 031;Klaricid;Biaxin (TN);(3R,4S,5S,6R,7R,9R,11R,12R,13R,14R)-6-(4-dimethylamino-3-hydroxy-6-methyl-oxan-2-yl)oxy-14-ethyl-12,13-dihydroxy-4-(5-hydroxy-4-methoxy-4,6-dimethyl-oxan-2-yl)oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione;Clarithromycine [INN-French];Clacine;Trovafloxacin & Clarithromycin;6-o-Methoxyerythromycin;(3R,4S,6R,7R,9R,11R,12R,13R,14R)-6-[(2S,3R,4S,6R)-4-dimethylamino-3-hydroxy-6-methyl-oxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-4-[(2S,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyl-oxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione;Abbott-56268;Clarith;Klacid;Claritromicina [INN-Spanish];Klaciped;6-O-Methylerythromycin A;Kofron;Heliclar;Klarin;TE-031;TE031;Maclar;Klaricid Pediatric;Biaxin;(3R,4S,5S,6R,7R,9R,11R,12R,13R,14R)-6-[(2S,3R,4S,6R)-4-dimethylamino-3-hydroxy-6-methyl-oxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-4-[(2S,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyl-oxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione;Helas;Veclam;Klarid;Clathromycin;Zeclar;Clarithromycinum [INN-Latin];Claribid;Klax;Mavid;

Article Data 13

Clarithromycin Synthetic route

118074-07-0

6-O-methylerythromycin A N-oxide

81103-11-9

clarithromycin

Conditions
ConditionsYield
Stage #1: 6-O-methylerythromycin A N-oxide With tin(ll) chloride In isopropyl alcohol at 30 - 40℃; for 2h;
Stage #2: With sodium hydrogencarbonate In water; isopropyl alcohol
96%
With bis(tri-n-butyltin) In tetrahydrofuran for 24h; Heating / reflux;95%
With hydrogen; W4 Raney-nickel In ethanol at 40 - 50℃; for 3h;92%
With potassium hydroxide; nickel-aluminum alloy In methanol; water at 35 - 40℃; for 3.5h;92%
Stage #1: 6-O-methylerythromycin A N-oxide With tin(ll) chloride In dichloromethane at 20℃; for 1.5h;
Stage #2: With sodium carbonate In dichloromethane; water
32%
930287-49-3

clarythromycin 9-O-(2-pyrimidyl)oxime

81103-11-9

clarithromycin

Conditions
ConditionsYield
With sodium hydrogensulfite In ethanol; water at 80℃; for 6h;95%
50-00-0

formaldehyd

118074-07-0

6-O-methylerythromycin A N-oxide

81103-11-9

clarithromycin

Conditions
ConditionsYield
Stage #1: 6-O-methylerythromycin A N-oxide With sodium hydrogensulfite In ethanol; water at 20℃; for 1h;
Stage #2: With sodium carbonate In ethanol; water
Stage #3: formaldehyd With formic acid; sodium carbonate more than 3 stages;
92%
Stage #1: 6-O-methylerythromycin A N-oxide With sodium hydrogensulfite In ethanol; water at 20℃; for 1h;
Stage #2: With sodium carbonate In ethanol; water
Stage #3: formaldehyd With formic acid; ammonia more than 3 stages;
30%
81103-11-9

clarithromycin

Conditions
ConditionsYield
With sodium disulfide In ethanol Heating;68%
130034-54-7

9-deoxo-9-imino-6-O-methylerythromycin A

81103-11-9

clarithromycin

Conditions
ConditionsYield
With water In methanol at 23℃; pH 12.4 or pH 7;
With hydrogenchloride; water In ethanol pH=5 - 6;

2',4''-[O-bis(trimethylsilyl)]clarithromycin 9-[O-(dimethylthexylsilyl)oxime]

81103-11-9

clarithromycin

Conditions
ConditionsYield
With sodium metabisulfite; formic acid In ethanol for 0.5h; Hydrolysis; Heating;4.32 g
930287-46-0

6-(4-dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-14-ethyl-7,12,13-trihydroxy-4-(5-hydroxy-4-methoxy-4,6-dimethyl-tetrahydro-pyran-2-yloxy)-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione 10-(O-pyrimidin-2-yl-oxime)

81103-11-9

clarithromycin

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: 90 percent / trimethylsilyl-imidazole / CH2Cl2 / 2 h / 0 °C
2: 83 percent / KOH / dimethylsulfoxide
3: 97 percent / HCO2H / ethanol; H2O
4: 95 percent / sodium hydrogen sulfite / ethanol; H2O / 6 h / 80 °C
View Scheme
930287-48-2

C48H88N4O13Si2

81103-11-9

clarithromycin

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 97 percent / HCO2H / ethanol; H2O
2: 95 percent / sodium hydrogen sulfite / ethanol; H2O / 6 h / 80 °C
View Scheme
930287-47-1

2',4''-O-bistrimethylsilyl erythromycin A 9-O-(2-pyrimydyl)oxime

81103-11-9

clarithromycin

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 83 percent / KOH / dimethylsulfoxide
2: 97 percent / HCO2H / ethanol; H2O
3: 95 percent / sodium hydrogen sulfite / ethanol; H2O / 6 h / 80 °C
View Scheme

erythromycin A (9E)-oxime hydrochloride

81103-11-9

clarithromycin

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: 93 percent / t-BuOK / 2 h / 80 °C
2: 90 percent / trimethylsilyl-imidazole / CH2Cl2 / 2 h / 0 °C
3: 83 percent / KOH / dimethylsulfoxide
4: 97 percent / HCO2H / ethanol; H2O
5: 95 percent / sodium hydrogen sulfite / ethanol; H2O / 6 h / 80 °C
View Scheme

Clarithromycin Specification

1. Introduction of Clarithromycin
Clarithromycin is one kind of white or almost white crystalline powder or colourless crystalline needles. The Systematic (IUPAC) name of this chemical is (3R,4S,5S,6R,7R,9R,11S,12R,13S,14S)-6-{[(2S,3R,4S,6R) -4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy} -14-ethyl-12,13-dihydroxy-4-{[(2R,4S,5S,6S)-5-hydroxy -4-methoxy-4,6-dimethyloxan-2-yl]oxy}-7 -methoxy-3,5,7,9,11,13-hexamethyl -1-oxacyclotetradecane-2,10-dione. The Classification Code of it is Anti-Bacterial Agents; Anti-Infective Agents; Antibacterial; Drug / Therapeutic Agent; Enzyme Inhibitors; Human Data; Protein synthesis inhibitors.

Clarithromycin belongs to Antibiotics;APIs;Antibiotics for Research and Experimental Use;Biochemistry;Macrolides (Antibiotics for Research and Experimental Use);Intermediates & Fine Chemicals;Pharmaceuticals;API's;1694 Pharmaceuticals&Personal Care Products;A - KAntibiotics;Antibacterial;Antibiotics A to;Antibiotics A-FAntibiotics;Chemical Structure Class;MacrolidesEPA;Neats;Spectrum of Activity. Besides, it should stored in -20°C Freezer.

2. Properties of Clarithromycin
Physical properties about Clarithromycin are:

(1)Index of Refraction: 1.526; (2)Molar Refractivity: 194 cm3; (3)Molar Volume: 631.9 cm3; (4)Density: 1.18 g/cm3; (5)Solubility: Insoluble; (6)Flash Point: 440.9 °C; (7)Melting Point: 217-220 °C; (8)Surface Tension: 48.7 dyne/cm; (9)Enthalpy of Vaporization: 133.36 kJ/mol; (10)Vapour Pressure: 5.06E-30 mmHg at 25 °C; (11)Boiling Point of 6-o-Methoxyerythromycin: 805.5 °C at 760 mmHg.

3. Structure Descriptors of Clarithromycin
(1)Canonical SMILES: CCC1C(C(C(C(=O)C(CC(C(C(C(C(C(=O)O1)C)OC2CC(C(C(O2)C)O)(C)OC)C)OC3C(C(CC
(O3)C)N(C)C)O)(C)OC)C)C)O)(C)O
(2)Isomeric SMILES: CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)O)(C)O
(3)InChI: InChI=1S/C38H69NO13/c1-15-26-38(10,45)31(42)21(4)28(40)19(2)17-37(9,47-14)33(52-35-29(41)25(39(11)12)16-20(3)48-35)22(5)30(23(6)34(44)50-26)51-27-18-36(8,46-13)32(43)24(7)49-27/h19-27,29-33,35,41-43,45H,15-18H2,1-14H3/t19-,20-,21+,22+,23-,24+,25+,26-,27+,29-,30+,31-,32+,33-,35+,36-,37-,38-/m1/s1
(4)InChIKey: AGOYDEPGAOXOCK-KCBOHYOISA-N

4. Toxicity of Clarithromycin

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LD oral > 5gm/kg (5000mg/kg) GASTROINTESTINAL: NAUSEA OR VOMITING

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BLOOD: HEMORRHAGE
Kiso to Rinsho. Clinical Report. Vol. 22, Pg. 1453, 1988.
mouse LD50 intraperitoneal 850mg/kg (850mg/kg) LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE
Chemotherapy Vol. 36(Suppl,
mouse LD50 intravenous 173mg/kg (173mg/kg)   Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 22, Pg. 769, 1991.
mouse LD50 oral 1230mg/kg (1230mg/kg) BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY) Kiso to Rinsho. Clinical Report. Vol. 22, Pg. 1433, 1988.
mouse LD50 subcutaneous > 5gm/kg (5000mg/kg) SKIN AND APPENDAGES (SKIN): CORROSIVE: AFTER TOPICAL EXPOSURE Chemotherapy Vol. 36(Suppl,
rat LD50 intraperitoneal 669mg/kg (669mg/kg) LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE
Chemotherapy Vol. 36(Suppl,
rat LD50 oral 1270mg/kg (1270mg/kg) BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY) Kiso to Rinsho. Clinical Report. Vol. 22, Pg. 1433, 1988.
rat LD50 subcutaneous > 5gm/kg (5000mg/kg) SKIN AND APPENDAGES (SKIN): CORROSIVE: AFTER TOPICAL EXPOSURE Chemotherapy Vol. 36(Suppl,
women TDLo oral 30mg/kg/3D-I (30mg/kg) CARDIAC: CHANGE IN RATE

CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP
Annals of Emergency Medicine. Vol. 30, Pg. 542, 1997.

5. Physical Properties of Clarithromycin

Physical Property Value Units Temp (deg C) Source
Melting Point 220 dec deg C   EXP
pKa Dissociation Constant 8.99 (none) 25 EXP
log P (octanol-water) 3.16 (none)   EXP
Water Solubility 0.342 mg/L 25 EST
Vapor Pressure 8.60E-27 mm Hg 25 EST
Henry's Law Constant 1.73E-29 atm-m3/mole 25 EST
Atmospheric OH Rate Constant 4.78E-10 cm3/molecule-sec 25 EST

6. Safety information of Clarithromycin
A poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion. Human systemic effects. When heated to decomposition it emits toxic vapors of NOx.
Hazard Codes: Xn,Xi
Risk Statements: 22-36/37/38
R22:Harmful if swallowed.
R36/37/38:Irritating to eyes, respiratory system and skin.
Safety Statements: 26-36
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
S36:Wear suitable protective clothing.
RTECS: KF4997000

The first aid is as following. Such as: When on the skin: first, should flush skin with plenty of water immediately for at least 15 minutes while removing contaminated clothing. Secondly, get medical aid. Or in the eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Then get medical aid soon. While, it's inhaled: Remove from exposure and move to fresh air immediately. Give artificial respiration while not breathing. When breathing is difficult, give oxygen. And as soon as to get medical aid. Then you have the ingesting of the product : Wash mouth out with water, and get medical aid immediately. In addition, it should be stored only in original container, or keep its container tightly closed.

7. Uses of Clarithromycin
The usage of Clarithromycin (CAS NO.81103-11-9) is a semi-synthetic macrolide antibiotic, a derivative of erythromycin. And it is a macrolide antibiotic used to treat upper and lower respiratory tract infections, skin and soft tissue infections. Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia, skin and skin structure infections. In addition, it is sometimes used to treat legionellosis, Helicobacter pylori, and lyme disease.

8. Production of Clarithromycin
(1)Use Erythromycin as the raw material and get the methyl off amino by using hydrolysis.
(2)Then get it reaction with Benzyl chloroformate and protect 5-tetrahydropyran ring side-chain hydroxyl and amino.
(3)In the methyl iodide reaction of dimethyl sulfoxide and tetrahydrofuran, carry out six on the methylation of hydroxyl and deprotected by catalytic hydrogenolysis,then reaction with the amino-formaldehyde.
(4)Finally,it is reduced to methyl, named clarithromycin.

The detailed steps are as follows:

Production of Clarithromycin

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