51-05-8

Basic information

• Product Name: Procaine hydrochloride
• Synonyms: aminocaine;anadolor;anesthesol;anestil;atoxicocaine;Benzoicacid,4-amino-,2-(diethylamino)ethylester,monohydrochloride;benzoicacid,p-amino-,2-(diethylamino)ethylester,monohydrochloride;bernocaine
• CAS NO: 51-05-8
• Molecular Formula: C₁₃H₂₁N₂O₂*Cl
• Molecular Weight: 272.77
• EINECS: 200-077-2
• Product Categories: Pharmaceutical;Sodium channel;APIS;Anesthetics;Pharmaceutical intermediate
• Mol File: 51-05-8.mol
• Article Data: 2

Chemical Properties

• Melting Point: 155-156 °C(lit.)
• Boiling Point: 195-196°C 17mm
• Flash Point: 195-196°C/17mm
• Appearance: Colorless to white/Crystals or Crystalline Powder
• Density: 1.1761 (rough estimate)
• Refractive Index: 1.5270 (estimate)
• Storage Temp.: room temp
• Solubility: Solution S is clear (2.2.1) and colourless (2.2.2, Method II).
• Water Solubility: soluble
• Sensitive: Air Sensitive
• Stability: Stable. Incompatible with strong oxidizing agents.
• Merck: 14,7757
• BRN: 3917802
• CAS DataBase Reference: Procaine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Procaine hydrochloride(51-05-8)
• EPA Substance Registry System: Procaine hydrochloride(51-05-8)

Safety Data

• Hazard Codes: T
• Statements: 25-43-36/37/38-23/24/25
• Safety Statements: 36/37/39-45-37/39-26
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: DG2275000
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 51-05-8(Hazardous Substances Data)

Usage

Description

Procaine hydrochloride, also called Novocain, or Novocaine, a topical anesthetic, which can block the nerve fiber conduction temporarilyand has a narcotic effect,strong effect, low toxicity, and non-addictive, but on the skin, mucosal penetration is weak, unsuitable for surface anesthesia, patients are used for infiltration, conduction and spinal anesthesia.The structure of procaine hydrochloride with aromatic primary amino, easy oxidation discoloration pH, temperature, UV, oxygen and metal ions can accelerate the oxidation discoloration. The aqueous solution was stable in pH3.0~5. So preparation of procaine hydrochloride injection, it generally takes add acid to regulate pH 3.3 to 5.5, and strictly control the sterilization temperature and time. to 100 ℃ steam sterilization 30min circulation is appropriate, and should pay attention to shading, sealed save.The above information is edited by the lookchem of Kui Xiongfeng.

Chemical Properties

Procaine hydrochloride is a white crystalline, odorless powder that is freely soluble in water, but less soluble in alcohol and almost insoluble in ether; solutions acid to litmus. Because the ester bond in the structure can be hydrolyzed to produce p-aminobenzoic acid and diethylaminoethanol, under certain conditions, p-aminobenzoic acid can be further decarboxylated to produce toxic aniline. Procaine hydrochloride has aromatic primary amino groups in its structure, which can be easily oxidized and discolored. pH, temperature, ultraviolet light, oxygen and metal ions can accelerate the oxidation and discoloration.

Uses

Procaine is a local anesthetic of the amino ester group that is primarily used as a topical anesthetic. Procaine is also used to control the pain of intramuscular injection of penicillin as well as in dentistry.

Application

Procaine hydrochloride has been used as a component of Krebs Henseleit buffer for incubating the left ventricular cardiac tissue in its resting length. It has also been used as an inducer in M9 media for induction assay. It is a sodium channel blocker and DNA methylation inhibitor.

Brand name

Novocain (Hospira).

General Description

Procaine hydrochloride is a synthetic compound that belongs to the class of local anesthetic drugs. It has a structure similar to the natural compounds that participate in nerve impulse transmission. It shows interaction with the cellular membranes causing membrane lipids to expand, membrane-bound calcium to displace and change the structure of the proteins that are responsible for regulating the cell permeability and shape.

Hazard

Toxic by ingestion.

Biochem/physiol Actions

Procaine is a Na+ channel blocker, commonly used as an anesthetic agent and is considered safer than cocaine. It is also useful as a painkiller to treat pain, associated with joints and tendons.

Contact allergens

Procaine is a local anesthetic with para-amino function. Sensitization mainly concerns the medical, dental, and veterinary professions.

Safety Profile

Poison by ingestion, subcutaneous, intravenous, and intraperitoneal routes. Human systemic effects: acute renal fdure. May have human reproductive effects. See also ESTERS. When heated to decomposition it emits very toxic fumes of HCl and NO,. Used as a local anesthetic.

Purification Methods

Novocain is recrystallised from aqueous EtOH. It is soluble at 25o in H2O (86.3%), EtOH (2.6%) and Me2CO (1%), it is slightly soluble in CHCl3, but is almost insoluble in Et2O. The anhydrous free base is recrystallised from ligroin or Et2O and has m 61o. [Einhorn Justus Liebigs Ann Chem 371 125 1909, IR: Szymanski & Panzica J Amer Pharm Assoc 47 443 1958, Beilstein 14 IV 1138.]

Mode of action

Procaine Hydrochloride is the hydrochloride salt form of procaine, a benzoic acid derivative with local anesthetic and antiarrhythmic properties. Procaine binds to and inhibits voltage-gated sodium channels, thereby inhibiting the ionic flux required for the initiation and conduction of impulses. In addition, this agent increases electrical excitation threshold, reduces rate of rise of action potential and slows nerve impulse propagation thereby causing loss of sensation.

Precautions

Procaine hydrochloride is used for infiltration, nerve block, peridural and spinal anest sthesia. It is considered a fairly safe drug if suitable precautions are observed. However, as with any anesthetic， idiosyncrasy may be encountered. Slow administration and avoidance of accidental intravenous injection are advisable. In local administration, if increased sensitivity to procaine is suspected, as in patients with cardiac disease or endocrine disorders (such as hyperthyroidism), an initial small dose to test tolerance is recommended. (Physicians' Desk Reference, 35th ed, p. 695)

InChI:InChI=1/C13H20N2O2.ClH/c1-4-15(5-2)13(3,17)12(16)10-6-8-11(14)9-7-10;/h6-9,17H,4-5,14H2,1-3H3;1H

Synthetic route

water (7732-18-5) + 4-β-D-glucopyranosylamino-benzoic acid-(2-diethylamino-ethyl ester); hydrochloride → D-glucose (50-99-7) + procaine hydrochloride (51-05-8)

Conditions	Yield
at 20 - 100℃; Equilibrium constant;

sodium salicylate (54-21-7) + procaine hydrochloride (51-05-8) → procainium salicylate (4344-99-4)

Conditions	Yield
In water; acetone at 20℃;	98%

carbon dioxide (124-38-9) + procaine hydrochloride (51-05-8) → procainium hydrocarbonate

Conditions	Yield
With sodium hydrogencarbonate In water at -4 - 0℃; under 760.051 Torr; Product distribution / selectivity;	97.7%

myricetin (529-44-2) + procaine hydrochloride (51-05-8) → 6,8-bis{p-[2-(diethylamino)ethoxycarbonyl]benzeneazo}-3,3',4',5,5',7-hexahydroxyflavone

Conditions	Yield
Stage #1: procaine hydrochloride With hydrogenchloride; sodium acetate; sodium nitrite In water Diazotization; Stage #2: myricetin In ethanol; water at 25℃; Substitution;	95%

procaine hydrochloride (51-05-8) → 2-diethylaminoethyl 4-amino-3-chlorobenzoate

Conditions	Yield
With N-chloro-succinimide; 2,2,6,6-tetramethylpiperidin-1-oxoammonium trifluoromethanesulfonate In chloroform at 25℃; for 12h; Reagent/catalyst; Schlenk technique;	95%

procaine hydrochloride (51-05-8) + N,N-diethyl-1,1,1-trimethylsilanamine (996-50-9) → N,N'-Diethylaminoethyl-p-aminobenzoxytrimethylsilane (76064-19-2)

Conditions	Yield
With triethylamine for 2h; Heating;	82%

procaine hydrochloride (51-05-8) + sodium 2-(4-isobutylphenyl)propionate (31121-93-4) → C13H20N2O2*C13H18O2

Conditions	Yield
In water at 20℃; for 2h;	79.1%

3-Acetyl-4,5,5-trimethyl-Δ3-butenolide (13156-10-0) + procaine hydrochloride (51-05-8) → 4-[1-(4,5,5-Trimethyl-2-oxo-2,5-dihydro-furan-3-yl)-eth-(E)-ylideneamino]-benzoic acid 2-diethylamino-ethyl ester (82814-30-0)

Conditions	Yield
With sodium In ethanol for 4h; Heating;	54.4%

3-acetyl-2-oxo-4,5-dihydrofuran (517-23-7) + procaine hydrochloride (51-05-8) → 4-[1-(2-oxo-tetrahydro-[3]furyl)-ethylLiDenamino]-benzoic acid-(2-diethylamino-ethyl ester)

Conditions	Yield
at 150℃;

D-glucose (50-99-7) + procaine hydrochloride (51-05-8) → 4-β-D-glucopyranosylamino-benzoic acid-(2-diethylamino-ethyl ester) (47593-05-5)

Conditions	Yield
With ethanol
With water

2-Bromo-1-(3,4-dimethoxyphenyl)ethanone (1835-02-5) + procaine hydrochloride (51-05-8) → 4-(3,4-dimethoxy-phenacylamino)-benzoic acid-(2-diethylamino-ethyl ester)

Conditions	Yield
With water

p-hydroxyphenacyl chloride (6305-04-0) + procaine hydrochloride (51-05-8) → 4-(4-hydroxy-phenacylamino)-benzoic acid-(2-diethylamino-ethyl ester)

Conditions	Yield
With water

procaine hydrochloride (51-05-8) → 4-amino-3-bromo-benzoic acid-(2-diethylamino-ethyl ester)

Conditions	Yield
With water; bromine

procaine hydrochloride (51-05-8) + methyl chloroformate (79-22-1) → 4-methoxycarbonylamino-benzoic acid-(2-diethylamino-ethyl ester); hydrochloride (97441-57-1)

procaine hydrochloride (51-05-8) + α-bromoacetophenone (70-11-1) → 4-phenacylamino-benzoic acid-(2-diethylamino-ethyl ester)

Conditions	Yield
With water

2,5,8,11,14-pentaoxa-pentadecanedioyl chloride (42021-85-2) + procaine hydrochloride (51-05-8) → C36H54N4O11 (41562-67-8)

Conditions	Yield
With triethylamine In chloroform

benzaldehyde (4-phenyl-selenazol-2-yl)-hydrazone (87385-94-2) + procaine hydrochloride (51-05-8) → 4-(4-Phenyl-2-{N'-[1-phenyl-meth-(Z)-ylidene]-hydrazino}-selenazol-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester (109054-36-6)

Conditions	Yield
With hydrogenchloride; sodium nitrite 1.) 0 deg C, 2.) EtOH, 0-5 deg C; Yield given. Multistep reaction;

thiazolo[3,2-a]benzimidazol-3(2H)-one (3042-01-1) + procaine hydrochloride (51-05-8) → 4-(3-Oxo-2,3-dihydro-benzo[4,5]imidazo[2,1-b]thiazol-2-ylazo)-benzoic acid 2-diethylamino-ethyl ester; hydrochloride (107106-86-5)

Conditions	Yield
With sodium nitrite 1) glacial acetic acid, H2O, 0 deg C, 2) dioxane, 2 h, 5 deg C; Yield given. Multistep reaction;

procaine hydrochloride (51-05-8) + s-trans-((2trans-4trans)-5-(4-dimethylaminophenyl)phenyl)penta-2,4-dienal (20432-36-4) → C26H33N3O2*H(1+)

Conditions	Yield
With hydrogenchloride In methanol for 0.166667h;

procaine hydrochloride (51-05-8) + 2-hydroxy-benzaldehyde (4-phenyl-selenazol-2-yl)-hydrazone (109054-52-6) → 4-(2-{N'-[1-(2-Hydroxy-phenyl)-meth-(Z)-ylidene]-hydrazino}-4-phenyl-selenazol-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester (109081-52-9)

Conditions	Yield
With hydrogenchloride; sodium nitrite 1.) 0 deg C, 2.) EtOH, 0-5 deg C; Yield given. Multistep reaction;

procaine hydrochloride (51-05-8) + 4-phenyl-[2-(4-metoxy-benzyliden)-hydrazinyl]-1,3-selenazole (109054-53-7) → 4-(2-{N'-[1-(4-Methoxy-phenyl)-meth-(Z)-ylidene]-hydrazino}-4-phenyl-selenazol-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester (109054-37-7)

Conditions	Yield
With hydrogenchloride; sodium nitrite 1.) 0 deg C, 2.) EtOH, 0-5 deg C; Yield given. Multistep reaction;

procaine hydrochloride (51-05-8) + 4-hydroxy-3-methoxy-benzaldehyde (4-phenyl-selenazol-2-yl)-hydrazone (109054-54-8) → 4-(2-{N'-[1-(3-Hydroxy-4-methoxy-phenyl)-meth-(Z)-ylidene]-hydrazino}-4-phenyl-selenazol-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester

Conditions	Yield
With hydrogenchloride; sodium nitrite 1.) 0 deg C, 2.) EtOH, 0-5 deg C; Yield given. Multistep reaction;

procaine hydrochloride (51-05-8) + 3-Benzylthiazolidin-2-one-4-thione (95213-81-3) → 4-(3-Benzyl-2-oxo-4-thioxo-thiazolidin-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester; hydrochloride (117014-20-7)

Conditions	Yield
With sodium nitrite 1.) acetic acid, water, 0-5 deg C, 10 min, 2.) dioxane, 0 deg C, 2 h; Yield given. Multistep reaction;

procaine hydrochloride (51-05-8) + 5-Carbamoyl-2-methoxy-benzoyl chloride (60795-47-3) → 4-(5-Carbamoyl-2-methoxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (89366-52-9)

Conditions	Yield
With triethylamine In tetrahydrofuran for 3h; Heating; Yield given;

procaine hydrochloride (51-05-8) + 5-Carbamoyl-2-octyloxy-benzoyl chloride → 4-(5-Carbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (89366-50-7)

Conditions	Yield
With triethylamine In tetrahydrofuran for 3h; Heating; Yield given;

procaine hydrochloride (51-05-8) + 2-Methoxy-5-octylcarbamoyl-benzoyl chloride → 4-(2-Methoxy-5-octylcarbamoyl-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (89366-60-9)

Conditions	Yield
With triethylamine In tetrahydrofuran for 3h; Heating; Yield given;

procaine hydrochloride (51-05-8) + 5-Isopropylcarbamoyl-2-octyloxy-benzoyl chloride → 4-(5-Isopropylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (89366-57-4)

Conditions	Yield
With triethylamine In tetrahydrofuran for 3h; Heating; Yield given;

procaine hydrochloride (51-05-8) + 5-Isobutylcarbamoyl-2-octyloxy-benzoyl chloride → 4-(5-Isobutylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (89366-51-8)

Conditions	Yield
With triethylamine In tetrahydrofuran for 3h; Heating; Yield given;

procaine hydrochloride (51-05-8) + 5-Cyclohexylcarbamoyl-2-octyloxy-benzoyl chloride → 4-(5-Cyclohexylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (89366-53-0)

Conditions	Yield
With triethylamine In tetrahydrofuran for 3h; Heating; Yield given;

procaine hydrochloride (51-05-8) + 5-Octylcarbamoyl-2-octyloxy-benzoyl chloride → 4-(5-Octylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester (89366-59-6)

Conditions	Yield
With triethylamine In tetrahydrofuran for 3h; Heating; Yield given;

procaine hydrochloride (51-05-8) → Procainperiodid

Conditions	Yield
With iodine; potassium iodide In ethanol

Upstream product

• 7732-18-5 water 

Downstream Products

• 97441-57-1 4-methoxycarbonylamino-benzoic acid-(2-diethylamino-ethyl ester); hydrochloride 
• 109081-52-9 4-(2-{N'-[1-(2-Hydroxy-phenyl)-meth-(Z)-ylidene]-hydrazino}-4-phenyl-selenazol-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester 
• 109054-37-7 4-(2-{N'-[1-(4-Methoxy-phenyl)-meth-(Z)-ylidene]-hydrazino}-4-phenyl-selenazol-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester 
• 117014-20-7 4-(3-Benzyl-2-oxo-4-thioxo-thiazolidin-5-ylazo)-benzoic acid 2-diethylamino-ethyl ester; hydrochloride 
• 89366-52-9 4-(5-Carbamoyl-2-methoxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester 
• 89366-50-7 4-(5-Carbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester 
• 89366-60-9 4-(2-Methoxy-5-octylcarbamoyl-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester 
• 89366-57-4 4-(5-Isopropylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester 
• 89366-51-8 4-(5-Isobutylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester 
• 89366-53-0 4-(5-Cyclohexylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester 
• 89366-59-6 4-(5-Octylcarbamoyl-2-octyloxy-benzoylamino)-benzoic acid 2-diethylamino-ethyl ester 
• 4344-99-4 procainium salicylate 
• 1620999-46-3 C₁₃H₂₀N₂O₂*ClH*C₆H₂Cl₂O₄ 
• 150398-17-7 β-cyclodextrin 

Relevant articles and documents

CARDIOPLEGIC SOLUTION

The present invention relates to a new cardioplegic solution to arrest and protect the heart muscle during surgery. The cardioplegic solution according to the invention offers several significant advantages as compared to standard available solutions, and contains magnesium sulfate heptahydrate, potassium chloride, procaine hydrochloride and xylitol.