7133-90-6

Basic information

• Product Name: 2-HYDROXY-THIOBENZAMIDE
• Synonyms: 2-HYDROXY-THIOBENZAMIDE;2-hydroxybenzothiamide;thio-salicylamid;2-HYDROXYTHIOBENZAMIDE 98%;Salicylamide, thio-
• CAS NO: 7133-90-6
• Molecular Formula: C₇H₇NOS
• Molecular Weight: 153.2
• Mol File: 7133-90-6.mol
• Article Data: 18

Chemical Properties

• Melting Point: 119 °C
• Boiling Point: 300.009 °C at 760 mmHg
• Flash Point: 135.241 °C
• Appearance: /
• Density: 1.339 g/cm³
• Vapor Pressure: 0.011mmHg at 25°C
• Refractive Index: 1.655
• CAS DataBase Reference: 2-HYDROXY-THIOBENZAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-HYDROXY-THIOBENZAMIDE(7133-90-6)
• EPA Substance Registry System: 2-HYDROXY-THIOBENZAMIDE(7133-90-6)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 7133-90-6(Hazardous Substances Data)

Usage

Uses

2-?Hydroxythiobenzamide is a reagent used in the preparation of thiazole-based chemosensors.

InChI:InChI=1/C7H7NOS/c8-7(10)5-3-1-2-4-6(5)9/h1-4,10H,8H2/b7-5+

Synthetic route

salicylonitrile (611-20-1) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
With O,S-diethyl-dithiophosphoric acid In water at 80℃; for 6h;	80%
With O,O-Diethyl hydrogen phosphorodithioate In methanol at 80℃; for 12h;	55%
With hydrogen sulfide; triethylamine In pyridine

salicylonitrile (611-20-1) + O,O-Diethyl hydrogen phosphorodithioate (298-06-6) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
In water at 80℃; for 6h;	80%

(EtO)2 P(S)SH + m-cyanophenol (873-62-1) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
In water	57%

salicylonitrile (611-20-1) + aq. NaCl + (EtO)2 P(S)SH + dichloromethane (75-09-2) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
With sodium hydrogencarbonate In water	55%

salicylamide (65-45-2) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
With Lawessons reagent In tetrahydrofuran at 55℃; for 4h; Inert atmosphere;	50%
With Lawessons reagent In tetrahydrofuran	29%
With tetraphosphorus decasulfide

ethylenediamine (107-15-3) + 6,6'-(1,2,4-Dithiazolidin-3,5-yliden)-bis-2,4-cyclohexadien-1-on (63963-47-3) → 2-(2-imidazolinyl)phenol (1565-39-5) + 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
Yields of byproduct given;	A n/a B 15%
Yield given. Yields of byproduct given;
Mechanism;

2-(2-Hydroxyphenyl)-1,3-benzoxazin-4-thion (79576-70-8) + ethylenediamine (107-15-3) → 2-(2-imidazolinyl)phenol (1565-39-5) + 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
Yield given;

6,6'-(1,2,4-Dithiazolidin-3,5-yliden)-bis-2,4-cyclohexadien-1-on (63963-47-3) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: various solvent(s) / 180 °C View Scheme

2-hydroxy-benzoic acid ethyl ester (118-61-6) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: alcohol; ammonia / 100 °C 2: P2S5 View Scheme

methyl salicylate (119-36-8) → 2-hydroxythiobenzamide (7133-90-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: alcohol; ammonia / 100 °C 2: P2S5 View Scheme

ethyl (2-chloroaceto)acetate (638-07-3) + 2-hydroxythiobenzamide (7133-90-6) → <2-(2-hydroxyphenyl)-4-thiazolyl>acetic acid ethyl ester (171017-45-1)

Conditions	Yield
In tetrahydrofuran for 60h; Heating;	93%

dichloromethane (75-09-2) + ethyl (2-chloroaceto)acetate (638-07-3) + 2-hydroxythiobenzamide (7133-90-6) → <2-(2-hydroxyphenyl)-4-thiazolyl>acetic acid ethyl ester (171017-45-1)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran	93%

3-bromoacetylcoumarin (29310-88-1) + 2-hydroxythiobenzamide (7133-90-6) → 2-(2-hydroxyphenyl)-4-(3-coumarinyl)thiazole (175654-92-9)

Conditions	Yield
In ethanol for 2h; Reflux;	90%

2-hydroxythiobenzamide (7133-90-6) → 6,6'-(1,2,4-Dithiazolidin-3,5-yliden)-bis-2,4-cyclohexadien-1-on (63963-47-3)

Conditions	Yield
With bromine In chloroform	88%

bromomethyl 2-methoxyphenyl ketone (31949-21-0) + 2-hydroxythiobenzamide (7133-90-6) → C16H13NO2S

Conditions	Yield
In ethanol for 4h; Hantzsch Thiazole Synthesis; Reflux;	88%

4-bromocrotonic ethyl ester (6065-32-3) + 2-hydroxythiobenzamide (7133-90-6) → C13H15NO3S

Conditions	Yield
With 1,1,1,3',3',3'-hexafluoro-propanol; sodium acetate for 8h; Reflux;	88%

2-bromo-1-(5-nitro-[2]furyl)-ethanone (15057-21-3) + 2-hydroxythiobenzamide (7133-90-6) → 2-[4-(5-Nitro-furan-2-yl)-thiazol-2-yl]-phenol

Conditions	Yield
In ethanol Heating;	85%

2-hydroxythiobenzamide (7133-90-6) + α-bromoacetophenone (70-11-1) → 2-(2'-hydroxyphenyl)-4-phenylthiazole

Conditions	Yield
In ethanol for 2h; Reflux;	84%
In ethanol at 20℃; for 5h;	84%
In ethanol Reflux;

methanol-dichloromethane + 2-hydroxythiobenzamide (7133-90-6) + ethyl bromoacetate (105-36-2) → 2-ethoxycarbonylmethylthiobenzamide

Conditions	Yield
With potassium carbonate In N-methyl-acetamide	83.4%

hydrotris(3,5-methylphenylpyrazolyl)boratozinc(II) hydroxide + 2-hydroxythiobenzamide (7133-90-6) + benzene (71-43-2) → Zn(hydrotris(3,5-phenylmethylpyrazolyl)borate)(salicylthioamide)*benzene

Conditions	Yield
In methanol; dichloromethane Zn-complex was dissolved in CH2Cl2, ligand in MeOH was added, stirred atroom temp. overnight under N2; evapd. to dryness on rotary evaporator, dissolved in benzene, filtered, recrystd. by diffusion with pentane; elem. anal.;	81.2%

2-hydroxythiobenzamide (7133-90-6) + 1,4-Dibromo-butane-2,3-dione (6305-43-7) → C18H12N2O2S2 (1242469-32-4)

Conditions	Yield
In ethanol for 12h; Hantzsch condensation; Reflux;	80%

ethyl (2-chloroaceto)acetate (638-07-3) + 2-hydroxythiobenzamide (7133-90-6) + 3-hydroxybenzenecarbothioamide (104317-54-6) → <2-(3-hydroxyphenyl)-4-thiazolyl>acetic acid ethyl ester (171017-48-4)

Conditions	Yield
In tetrahydrofuran	78%

ethyl Bromopyruvate (70-23-5) + 2-hydroxythiobenzamide (7133-90-6) → ethyl 2-(2-hydroxyphenyl)thiazole-4-carboxylate (27383-13-7)

Conditions	Yield
In ethanol for 2h; Hantzsch Thiazole Synthesis; Reflux;	71%
In ethanol	52%

2-Bromoacetylpyridine (40086-66-6) + 2-hydroxythiobenzamide (7133-90-6) → C14H10N2OS (1191385-37-1)

Conditions	Yield
In ethanol for 2h; Reflux;	70%

2-hydroxythiobenzamide (7133-90-6) + 3-(2-bromoacetyl)-7-(diethylamino)-2H-chromen-2-one (88735-44-8) → 2-(2-hydroxyphenyl)-4-[7-(diethylamino)coumarinyl]thiazole (1299474-80-8)

Conditions	Yield
In ethanol for 2h; Reflux;	68%

ethyl 2-cyano-3,3-di(methylsulfanyl)acrylate (17823-58-4) + 2-hydroxythiobenzamide (7133-90-6) → 5-ethoxycarbonyl-2-(2-hydroxyphenyl)-6-imino-4-methylsulfanyl-6H-1,3-thiazine hydroperchlorate

Conditions	Yield
With perchloric acid In acetic acid at 60℃; for 0.5h;	67%

2-hydroxythiobenzamide (7133-90-6) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2–(5-(4-methoxyphenyl)thiazol-2-yl)phenol

Conditions	Yield
In ethanol for 4h; Inert atmosphere; Reflux;	63%
In ethanol for 4h; Inert atmosphere; Reflux;

2-hydroxythiobenzamide (7133-90-6) + 2-Bromo-2'-acetonaphthone (613-54-7) → 2-(2-hydroxyphenyl)-4-(2-naphthyl)thiazole

Conditions	Yield
In ethanol for 7h; Reflux;	60%

2-hydroxythiobenzamide (7133-90-6) + 1-(bromoacetyl)pyrene (80480-15-5) → 2-(2-hydroxyphenyl)-4-(pyren-1-yl)thiazole

Conditions	Yield
In ethanol for 7h; Reflux;	58%

2-bromo-1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-1-ethanone (7520-95-8) + 2-hydroxythiobenzamide (7133-90-6) → 2-(4′-methyl-2′-phenyl-4,5′-bisthiazol-2-yl)phenol

Conditions	Yield
In acetone at 20℃; for 24h; Hantzsch Thiazole Synthesis;	16%

2-hydroxythiobenzamide (7133-90-6) → salicylonitrile (611-20-1)

Conditions	Yield
bei der Destillation unter vermindertem Druck;

2-hydroxythiobenzamide (7133-90-6) → 1,3-benzoxazine-2,4-dione (2037-95-8)

Conditions	Yield
With potassium hydroxide; dihydrogen peroxide

2-hydroxythiobenzamide (7133-90-6) → N',2-dihydroxybenzimidamide (6005-58-9)

Conditions	Yield
With ethanol; hydroxylamine hydrochloride; sodium carbonate
Multi-step reaction with 2 steps 1: bei der Destillation unter vermindertem Druck 2: alcohol; sodium carbonate; hydroxylamine hydrochloride / 90 °C / unter Druck View Scheme

Upstream product

• 611-20-1 salicylonitrile 
• 298-06-6 O,O-Diethyl hydrogen phosphorodithioate 
• 79576-70-8 2-(2-Hydroxyphenyl)-1,3-benzoxazin-4-thion 
• 107-15-3 ethylenediamine 
• 63963-47-3 6,6'-(1,2,4-Dithiazolidin-3,5-yliden)-bis-2,4-cyclohexadien-1-on 
• 873-62-1 m-cyanophenol 
• 75-09-2 dichloromethane 
• 119-36-8 methyl salicylate 
• 118-61-6 2-hydroxy-benzoic acid ethyl ester 
• 65-45-2 salicylamide 

Downstream Products

• 83053-38-7 2-(o-hydroxyphenyl)benzothiazol 
• 63963-47-3 3,5-bis-(2-hydroxy-phenyl)-[1,2,4]dithiazolylium betaine 
• 83053-37-6 4-Dimethoxymethyl-2-(o-hydroxyphenyl)-thiazol 
• 63963-47-3 C₁₄H₉NO₂S₂ 
• 63963-47-3 6,6'-(1,2,4-Dithiazolidin-3,5-yliden)-bis-2,4-cyclohexadien-1-on 
• 171017-45-1 <2-(2-hydroxyphenyl)-4-thiazolyl>acetic acid ethyl ester 
• 27501-91-3 2-(2-hydroxyphenyl)thiazole-4-carboxylic acid 
• 1191385-37-1 C₁₄H₁₀N₂OS 
• 171017-53-1 [2-(2-Methoxy-phenyl)-thiazol-4-yl]-acetic acid ethyl ester 
• 178765-31-6 <2-(2-methoxyphenyl)-4-thiazolyl>acetic acid 
• 171017-49-5 <2-(2-hydroxyphenyl)-4-thiazolyl>acetic acid 
• 611-20-1 salicylonitrile 
• 7783-06-4 hydrogen sulfide 
• 61636-48-4 2-Hydroxy-thiobenzimidic acid methyl ester 

Relevant articles and documents

Internal rotation and intramolecular hydrogen bonding in thiosalicylamide: gas phase electron diffraction study supported by quantum chemical calculations

The molecular structure of thiosalicylamide (2-hydroxythiobenzamide) was investigated in the gas phase at 401?K by means of gas electron diffraction (GED) combined with quantum chemical (QC) calculations. Special attention was paid to the internal rotation of the thioamide group. Structural refinement was performed taking into account rovibrational corrections to the thermal-average internuclear distances calculated with harmonic and anharmonic (cubic) MP2/cc-pVTZ force constants in terms of static and dynamic models. It was shown that both models fitted the GED data equally well. The results of the GED refinement revealed that in the equilibrium structure, the thioamide group is twisted by about 30° with respect to the phenol ring plane. This is the result of an interatomic repulsion of hydrogen atom in the amide group from the closest hydrogen atom of the benzene ring, which overcomes the energy gain from the π?π conjugation of the thioamide group and the aromatic system of thiosalicylamide. Natural bond orbital (NBO) analysis and comparison of the thiosalicylamide molecular structure with those of related compounds revealed hydrogen-bonded fragment between the hydroxyl and thiocarbonyl groups. The structure of thiosalicylamide in the gas phase was found to be markedly different from that in the solid phase due to the effect of intermolecular hydrogen bonding in the crystal.

METHOD OF MODULATING RIBONUCLEOTIDE REDUCTASE

A method of modulating ribonucleotide reductase activity in a neoplastic cell includes administering to the cell an amount of a hydrazone or hydrazine ribonucleotide reductase modulator (RRmod), the amount being effective to inhibit neoplastic cell growth.

Structure-guided design of anti-cancer ribonucleotide reductase inhibitors

Ribonucleotide reductase (RR) catalyses the rate-limiting step of dNTP synthesis, establishing it as an important cancer target. While RR is traditionally inhibited by nucleoside-based antimetabolites, we recently discovered a naphthyl salicyl acyl hydrazone-based inhibitor (NSAH) that binds reversibly to the catalytic site (C-site). Here we report the synthesis and in vitro evaluation of 13 distinct compounds (TP1-13) with improved binding to hRR over NSAH (TP8), with lower KD’s and more predicted residue interactions. Moreover, TP6 displayed the greatest growth inhibiting effect in the Panc1 pancreatic cancer cell line with an IC50 of 0.393 μM. This represents more than a 2-fold improvement over NSAH, making TP6 the most potent compound against pancreatic cancer emerging from the hydrazone inhibitors. NSAH was optimised by the addition of cyclic and polar groups replacing the naphthyl moiety, which occupies the phosphate-binding pocket in the C-site, establishing a new direction in inhibitor design.