299-35-4

Basic information

• Product Name: THIOTHIAMINE
• Synonyms: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methyl-2(3H)-Thiazolethione;Thiothlamine;sulbone;3-(4-Amino-2-methyl-5-pyrimidinylmethyl)-5-(2-hydroxyethyl)-4-methyl-4-thiazoline-2-thione;3-[(2-Methyl-4-amino-5-pyrimidinyl)methyl]-5-(β-hydroxyethyl)-4-methyl-4-thiazoline-2-thione;Solbone;Thiamin-2-thione;ThiaMin Thiothiazolone
• CAS NO: 299-35-4
• Molecular Formula: C₁₂H₁₆N₄OS₂
• Molecular Weight: 296.41
• EINECS: 206-077-9
• Product Categories: Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Impurities
• Mol File: 299-35-4.mol
• Article Data: 3

Chemical Properties

• Melting Point: 238-239 °C
• Boiling Point: 509.6 °C at 760 mmHg
• Flash Point: 262 °C
• Appearance: /
• Density: 1.42g/cm³
• Vapor Pressure: 3.28E-11mmHg at 25°C
• Refractive Index: 1.709
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Very Slightly, Heated)
• PKA: 14.72±0.10(Predicted)
• CAS DataBase Reference: THIOTHIAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: THIOTHIAMINE(299-35-4)
• EPA Substance Registry System: THIOTHIAMINE(299-35-4)

Safety Data

• Hazardous Substances Data: 299-35-4(Hazardous Substances Data)

Usage

Uses

Thiothiamine is an impurity of Thiamine (T344185). Thiothiamine inhibits the activity of glutamate decarboxylase and decreases the concentration of GABA in brain tissue. Thiamine Impurity A;

InChI:InChI=1/C12H16N4OS2/c1-7-10(3-4-17)19-12(18)16(7)6-9-5-14-8(2)15-11(9)13/h5,17H,3-4,6H2,1-2H3,(H2,13,14,15)

Synthetic route

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-3a-methyl-tetrahydro-furo[2,3-d]thiazole-2-thione (108669-31-4) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With hydrogenchloride

Aneurin (70-16-6) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With water; oxygen

1-thiopropane (107-03-9) + thiamine disulfide (100502-51-0) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With hydrogenchloride

diethyltetrasulfane (13730-34-2) + thiamine disulfide (100502-51-0) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
at 120℃;

thiamine disulfide (100502-51-0) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With 2-methyl-propan-1-ol; sulfur at 130℃;

carbon disulfide (75-15-0) + N-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-acetamide (23676-63-3) + 5-Acetoxy-3-chloropentan-2-one (13051-49-5) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
(i) aq. NaOH, (ii) /BRN= 971207/, /BRN= 1098293/, aq. NH3, EtOH, (iii) aq. HCl, (iV) aq. NaOH; Multistep reaction;

N-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-N-(4-hydroxy-1-methyl-2-thioxo-butyl)-formamide; sodium salt (4710-54-7) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With carbon dioxide; aniline In ethanol

Thiamine hydrochloride (67-03-8) → thiamine thiazolone (490-82-4) + 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With KO2 In dimethyl sulfoxide for 0.5h; Ambient temperature;

4-Nitro-benzenethiolate3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-2-(4-nitro-phenylsulfanyl)-thiazol-3-ium; (96643-11-7) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + thiochrome (92-35-3)

Conditions	Yield
In acetonitrile for 3h; Heating;

N-<(4-amino-2-methyl-5-pyrimidinyl)methyl>dithiocarbamate ammonium salt + 5-Acetoxy-3-chloropentan-2-one (13051-49-5) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With sodium iodide In water; N,N-dimethyl-formamide at 20℃; for 6h;

hydrogenchloride (7647-01-0) + 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-3a-methyl-tetrahydro-furo[2,3-d]thiazole-2-thione (108669-31-4) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

5-(aminomethyl)-2-methylpyrimidin-4-amine (95-02-3) + CS2 + (+-)-3-acetyl-3-chloro-dihydro-furan-2-one → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With sodium hydroxide; ammonia Erwaermen des Reaktionsprodukt mit wss. HCl;

5-(aminomethyl)-2-methylpyrimidin-4-amine (95-02-3) + 5-Acetoxy-3-chloropentan-2-one (13051-49-5) + CS2 → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
With methanol; ammonia Erwaermen des Reaktionsprodukts mit wss. HCl;

2-methyl-propan-1-ol (78-83-1) + N-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-N-(4-hydroxy-1-methyl-2-methyldisulfanyl-but-1-en-t-yl)-formamide (2281-20-1) → thiamine thiazolone (490-82-4) + 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + thiochrome

Conditions	Yield
at 120℃;

2-methyl-propan-1-ol (78-83-1) + thiamine disulfide (100502-51-0) → thiamine thiazolone (490-82-4) + 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + thiochrome

Conditions	Yield
at 120℃;

5-(aminomethyl)-2-methylpyrimidin-4-amine (95-02-3) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: concd. ammonia, NH3(gas) / ethanol / 3 h 2: NaI / dimethylformamide; H2O / 6 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: NH3; aqueous methanol. NaOH 2: methanol. sodium methylate 3: aqueous HCl View Scheme

thiamine hydrochloride (96643-07-1) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile / 3 h / Ambient temperature 2: acetonitrile / 3 h / Heating View Scheme

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-chloro-ethyl)-4-hydroxy-4-methyl-thiazolidine-2-thione (171090-99-6) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol. sodium methylate 2: aqueous HCl View Scheme

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-hydroxy-5-(2-hydroxy-ethyl)-4-methyl-thiazolidine-2-thione (1153-39-5) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous HCl 2: aqueous HCl View Scheme

butanoic acid anhydride (106-31-0) + 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) → 3-(4-butyrylamino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-butyryloxy-ethyl)-4-methyl-3H-thiazole-2-thione (103990-78-9)

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + pivaloyl chloride (3282-30-2) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-5-(2-pivaloyloxy-ethyl)-3H-thiazole-2-thione (103152-07-4)

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + acetic anhydride (108-24-7) → 5-(2-acetoxy-ethyl)-3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-3H-thiazole-2-thione (92325-11-6)

Conditions	Yield
With pyridine

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + acetic anhydride (108-24-7) → 5-(2-acetoxy-ethyl)-3-(4-acetylamino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-3H-thiazole-2-thione (101428-46-0)

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + acetic acid (64-19-7) → 5-(2-acetoxy-ethyl)-3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-3H-thiazole-2-thione (92325-11-6)

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + propionic acid (802294-64-0) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-5-(2-propionyloxy-ethyl)-3H-thiazole-2-thione

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + methanesulfonyl chloride (124-63-0) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-methanesulfonyloxy-ethyl)-4-methyl-3H-thiazole-2-thione (102882-02-0)

Conditions	Yield
With pyridine

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + propionic acid anhydride (123-62-6) → 4-methyl-3-(2-methyl-4-propionylamino-pyrimidin-5-ylmethyl)-5-(2-propionyloxy-ethyl)-3H-thiazole-2-thione (107559-36-4)

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + m-nitrobenzoic acid chloride (121-90-4) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-5-[2-(3-nitro-benzoyloxy)-ethyl]-3H-thiazole-2-thione (108395-74-0)

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + butyric acid (107-92-6) → 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-butyryloxy-ethyl)-4-methyl-3H-thiazole-2-thione (3286-65-5)

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) → thiamine thiazolone (490-82-4)

Conditions	Yield
With sodium hydroxide; dihydrogen peroxide

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) → Aneurin (70-16-6)

Conditions	Yield
With dihydrogen peroxide
With amalgamated magnesium
With aluminium
With nickel

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) → vitamin B1 (59-43-8)

Conditions	Yield
(i) aq. H2O2, (ii) aq. HCl; Multistep reaction;

3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) → vitamin B1 mononitrate (532-43-4)

Conditions	Yield
With dihydrogen peroxide; nitric acid

hydrogenchloride (7647-01-0) + 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-3H-thiazole-2-thione (299-35-4) + air oxygen + SO2 → Aneurin (70-16-6)

Conditions	Yield
Kinetics;

Upstream product

• 70-16-6 Aneurin 
• 67-03-8 Thiamine hydrochloride 
• 7647-01-0 hydrogenchloride 
• 108669-31-4 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-3a-methyl-tetrahydro-furo[2,3-d]thiazole-2-thione 
• 95-02-3 5-(aminomethyl)-2-methylpyrimidin-4-amine 
• 13051-49-5 5-Acetoxy-3-chloropentan-2-one 
• 78-83-1 2-methyl-propan-1-ol 
• 2281-20-1 N-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-N-(4-hydroxy-1-methyl-2-methyldisulfanyl-but-1-en-t-yl)-formamide 
• 100502-51-0 thiamine disulfide 
• 1153-39-5 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-hydroxy-5-(2-hydroxy-ethyl)-4-methyl-thiazolidine-2-thione 
• 171090-99-6 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-chloro-ethyl)-4-hydroxy-4-methyl-thiazolidine-2-thione 
• 96643-07-1 thiamine hydrochloride 
• 96643-11-7 4-Nitro-benzenethiolate3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-2-(4-nitro-phenylsulfanyl)-thiazol-3-ium; 
• 4710-54-7 N-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-N-(4-hydroxy-1-methyl-2-thioxo-butyl)-formamide; sodium salt 

Downstream Products

• 108395-74-0 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-5-[2-(3-nitro-benzoyloxy)-ethyl]-3H-thiazole-2-thione 
• 490-82-4 thiamine thiazolone 
• 59-43-8 vitamin B₁ 
• 532-43-4 vitamin B₁ mononitrate 

Relevant articles and documents

Secondary Deuterium Kinetic Isotope Effects in the Cleavage of Thiamin and N-Methylthiaminium Ion: First Evidence To Identify the Rate-Limiting Step

Thiamin and 1'-methylthiaminum ion deuterated at the 6'- and N-methylene positions were cleaved by sulfite ion in aqueous phosphate at 25 deg C.Observed secondary kinetic isotope effects (standard deviation of the ratio) were inverse for the 6'-position, 0.95 (0.09) and 0.95 (0.03), respectively, and normal for the N-methylene group., 1.08 (0.09) and 1.10 (0.03), respectively.These results confirm the multistep mechanism first proposed by us (J.Am.Chem.Soc. 1977, 99, 3134).They prove for the first time that sulfite ion adds to the 6'-position and that fragmentation of the CH2-thiazole bond in the resultant adduct contributes to the rate in the multistep mechanism.

REACTION OF N-ALKYLTHIAZOLIUM HALIDES, INCLUDING THIAMINE, WITH SUPEROXIDE ION. CHEMISTRY AND BIOLOGICAL IMPLICATIONS.

N-alkylthiazolium halides are transformed by KO2 into the corresponding thiazolin-2-ones and thiazolin-2-thiones; the same reactions occur with thiamine, whose thiazolin-2-one pyrophosphate has been reported to be a strong inhibitor of pyruvic dehydrogenase.