Trimethylsilyl isothiocyanate

Structural formula
General
Surname	Trimethylsilyl isothiocyanate
other names	Isocyanatotrimethylsilane Trimethylisocyanatosilane TMSNCS
Molecular formula	C 4 H 9 NSSi
Brief description	clear, light yellow liquid
External identifiers / databases
CAS number 2290-65-5 EC number 218-929-7 ECHA InfoCard 100.017.209 PubChem 75297 Wikidata Q56745091
properties
Molar mass	131.27 g mol −1
Physical state	liquid
density	0.9257 g cm −3 at 20 ° C 0.931 g cm −3 at 25 ° C
Melting point	<-32.8 ° C
boiling point	143 ° C
solubility	soluble in non-polar solvents, e.g. B. n-hexane or benzene
Refractive index	1.4809 (20 ° C) 1.482 (20 ° C)
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 226-301-311-315-319-331-334-335 P: 261-280-301 + 310-305 + 351 + 338-311
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Trimethylsilyl isothiocyanate can be understood as unstable isothiocyanic acid HNCS protected by the trimethylsilyl group - which is in tautomeric equilibrium with the likewise unstable thiocyanic acid HSCN. The compound is the starting material for thiocyanates and isothiocyanates , thioureas and nitrogen- and sulfur-containing (with the exception of 1,3,4-oxadiazole) heterocycles .

Manufacturing

Trimethylchlorosilane reacts with excess silver isothio-cyanate in inert solvents at 80 ° C. in approx. 85% crude yield to trimethylsilyl isothiocyanate. The reaction of anhydrous sodium thiocyanate NaSCN in a Soxhlet article with boiling chlorotrimethylsilane appears to be more advantageous in terms of preparation , in which trimethylisocyanatosilane is obtained in 78% yield after fractional distillation of the extraction mixture .

properties

Trimethylsilyl isothiocyanate is a clear, colorless to light yellow and unpleasantly pungent smelling liquid that reacts with water to decompose. Inconsistent isothiocyanic acid is formed with ethanol , which continues to react rapidly.

Applications

Thiocyanates and isothiocyanates

Trimethylsilyl isothiocyanate is suitable as a reagent for introducing thiocyanate and isothiocyanate groups as well as functional nitrogen-containing heterocycles.

Alkyl and aryl thiocyanates can be obtained under mild reaction conditions in sometimes very good yields (> 90%) by reacting TMSNCS with alkyl / aryl halides in the presence of the phase transfer catalyst tetrabutylammonium fluoride n-Bu ₄ NF.

The implementation of TMSNCS with aldehydes , such as. B. isobutanal in the presence of catalytic amounts provides the Lewis acid , zinc chloride ZnCl ₂ on the cyclic trioxane - trimer in high yield (89%) of an α, α'-di-isothiocyanatoether.

Nitrogen-containing five-membered heterocycles

In a variant of the Hantzsch thiazole synthesis , thioureas substituted with trimethylsilyl isothiocyanate and aromatic or primary and secondary aliphatic amines are formed, which can be cyclized with α-bromocarbonyl compounds to give 2-aminothiazoles. As a multicomponent reaction , this reaction can also be carried out by adding TMSNCS, the base triethylamine and an amine to an α-bromoketone in ethanol .

2-aminothiazoles are versatile synthetic building blocks for active pharmaceutical ingredients, such as. As the H ₂ -receptor antagonist famotidine , the cephalosporin - antibiotic Cefdinir , the nonsteroidal anti-inflammatory drug meloxicam or the protein kinase inhibitor dasatinib .

3-Mercapto-1,2,4-triazoles are formed in the reaction of TMSNCS with carboxylic acid hydrazides via the intermediate stage of thiosemicarbazides through their cyclization using sodium hydroxide solution .

3-Mercapto-1,2,4-triazoles are building blocks for active ingredients with different pharmacological activities.

2-Amino-1,3,4-thiadiazoles can be obtained in high yields in a one-pot reaction of TMSNCS with acid hydrazides in ethanol in the presence of concentrated sulfuric acid .

2-Amino-1,3,4-thiadiazole is the basic structure for the carbonic anhydrase inhibitor acetazolamide , the nitroimidazole megazole against Chagas disease and African trypanosomiasis , as well as for antimicrobial substances with a different spectrum of activity.

Analogous to this are 2-amino-1,3,4-oxadiazoles by the one-pot reaction of TMSNCS with acid hydrazides in ethanol and the addition of an alkaline iodine / potassium iodide solution, the intermediate thiosemicarbazide being converted into the corresponding product with cyclization and sulfur elimination (cyclodesulfurization) in high yield Aminooxadiazole passes over.

Derivatives of 2-amino-1,3,4-oxadiazole also show diverse pharmacological properties.

Further reactions by TMSNCS to introduce the isocyanate group, e.g. B. in the conversion of alkenes into diisocyanates are reported.

Individual evidence

1. ↑ ^{a b c d e f g h} data sheet trimethylsilyl isothiocyanate from Sigma-Aldrich , accessed on August 25, 2018 ( PDF ).
2. ↑ ^{a b} Patent GB643941 : Improvements in and relating to organo-silicon compounds. Filed on September 27, 1950 , published on June 9, 1948 , Applicant: The British Thomson-Houston Co. Ltd ..
3. ↑ ^{a b c} H.H. Anderson: Methyl silicon isothiocyanates. Molar refractions . In: J. Am. Chem. Soc. tape 69 , no. 12 , 1947, pp. 3049–3051 , doi : 10.1021 / ja01204a036 .
4. ↑ RHCN Freitas: trimethylsilyl isothiocyanate (TMSNCS) . In: Austr. J. Chem. Band 69 , no. 8 , 2016, p. 928-929 , doi : 10.1071 / CH16057 .
5. ↑ Patent GB643941 : Improvements in and relating to organo-silicon compounds. Filed on June 9, 1948 , published on September 27, 1950 , Applicant: The British Thomson-Houston Co. Ltd ..
6. ↑ ^{a b} V. Golubev, F. Zubkov, M. Krasavin: A simple, three-component synthesis of 2-aminothiazoles using trimethylsilyl isothiocyanate . In: Tetrahedron Lett. tape 54 , 2013, p. 4844-4847 , doi : 10.1016 / j.tetlet.2013.06.102 .
7. ↑ P.-Y. Renard, H. Schwebel, P. Vayron, E. Leclerc, S. Dias, C. Mioskowski: Optimized access to alkyl thiocyanates . In: Tetrahedron Lett. tape 42 , no. 48 , 2001, p. 8479-8481 , doi : 10.1016 / S0040-4039 (01) 01846-9 .
8. ↑ K. Nishiyama, M. Oba: Reactions of trimethylsilyl isothiocyanate with aldehydes and acetals. Synthesis of symmetrically and unsymmetrically isothiocyanato-substituted ethers . In: Bull. Chem. Soc. Jpn. tape 60 , no. 6 , 1987, pp. 2289-2291 , doi : 10.1246 / bcsj.60.2289 .
9. ↑ D. Das, P. Sikdar, M. Bairaqi: Recent developments of 2-amino-thiazoles in medicinal chemistry . In: Eur. J. Med. Chem. Volume 109 , 2016, p. 89-98 , doi : 10.1016 / j.ejmech.2015.12.022 .
10. ↑ ^{a b} D.R. Guda, T. Wang, HM Cho, ME Lee: Trimethylsilyl isothiocyanate (TMSNCS): an efficient reagent for the one-pot synthesis of mercapto-1,2,4-triazoles . In: Tetrahedron Lett. tape 53 , no. 39 , 2012, p. 5238-5242 , doi : 10.1016 / j.tetlet.2012.07.054 .
11. ↑ RM Shaker: The chemistry of mercapto- and thione-substituted 1,2,4-triazoles and their utility in heterocyclic synthesis . In: ARKIVOC . tape 9 , 2006, p. 59-112 , doi : 10.3998 / ark.55550190.0007.904 .
12. ↑ DR Guda, HM Cho, ME Lee: Mild and convenient one-pot synthesis of 2-amino-1,3,4-thiadiazoles using trimethylsilyl isothiocyanate (TMSNCS) . In: RSC Adv. Band 3 , 2013, p. 6813-6816 , doi : 10.1039 / c3ra00159h .
13. ↑ G. Serban, O. Stanasel, E. Serban, S. Bota: 2-Amino-1,3,4-thiadiazoles as a potential scaffold for promising antimicrobial agents . In: Drug Des. Dev. Ther. tape 12 , 2018, p. 1545-1566 , doi : 10.2147 / DDDT.S155958h .
14. ↑ ^{a b} D.R. Guda, HM Cho, ME Lee: Mild and convenient one-pot synthesis of 2-amino-1,3,4-oxadiazoles promoted by trimethylsilyl isothiocyanate (TMSNCS) . In: RSC Adv. Band 3 , 2013, p. 7684-7687 , doi : 10.1039 / c3ra41044g .
15. ↑ M. Bruno, R. Margarita, L. Parlanti, G. Piancatelli, M. Trifoni: Hypervalent iodine chemistry: Novel and direct thiocyanation of alkenes using [bis (acetoxy) iodo] benzene / trimethylsilyl isothiocyanate reagent combination. Synthesis of 1,2-dithiocyanates . In: Tetrahedron Lett. tape 39 , no. 22 , 1998, pp. 3847-3848 , doi : 10.1016 / S0040-4039 (98) 00629-7 .