18107-18-1

Basic information

• Product Name: (TRIMETHYLSILYL)DIAZOMETHANE
• Synonyms: (trimethylsilyl)diazomethanesolution;(DIAZOMETHYL)TRIMETHYLSILANE;TMS-DIAZOMETHANE;(TRIMETHYLSILYL)DIAZOMETHANE;(TRIMETHYLSILYL)DIAZOMETHANE, 2.0 M IN D;(TRIMETHYLSILYL)DIAZOMETHANE, 2.0M SOLUT ION IN HEXANES;(TRIMETHYLSILYL)DIAZOMETHANE SOLUTION, ~2 M IN HEXANE;Trimethylsilyldiazomethane2.0MINdiethylester
• CAS NO: 18107-18-1
• Molecular Formula: C₄H₁₀N₂Si
• Molecular Weight: 114.22
• Product Categories: Analytical Chemistry;Diazomethane Precursors & Equivalents (GC Derivatizing Reagents);Esterification & Alkylation (GC Derivatizing Reagents);GC Derivatizing Reagents;Si (Classes of Silicon Compounds);Si-(C)4 Compounds;Silicon Compounds (for Synthesis);Synthetic Organic Chemistry
• Mol File: 18107-18-1.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 96 °C
• Flash Point: −31 °F
• Appearance: White/Solution
• Density: 0.773 g/mL at 25 °C
• Refractive Index: 1.4362
• Storage Temp.: Refrigerator
• Solubility: Sol most organic solvents; insol H2O.
• Water Solubility: Immiscible with water. Miscible with organic solvents.
• Sensitive: Moisture & Light Sensitive
• Stability: Shock Sensitive
• BRN: 1902903
• CAS DataBase Reference: (TRIMETHYLSILYL)DIAZOMETHANE(CAS DataBase Reference)
• NIST Chemistry Reference: (TRIMETHYLSILYL)DIAZOMETHANE(18107-18-1)
• EPA Substance Registry System: (TRIMETHYLSILYL)DIAZOMETHANE(18107-18-1)

Safety Data

• Hazard Codes: F+,Xn,N,F,T,T+
• Statements: 12-19-22-66-67-65-62-51/53-48/20-38-11-23-39/26-26-45
• Safety Statements: 9-16-29-33-36/37-61-62-45-28-53
• RIDADR: UN 1208 3/PG 2
• WGK Germany: 3
• F: 10
• TSCA: Yes
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 18107-18-1(Hazardous Substances Data)

Usage

Description

(TRIMETHYLSILYL)DIAZOMETHANE is a clear yellow solution that serves as a non-explosive substitute for diazomethane. It is primarily used for the homologation of carbonyl derivatives, such as ketones, through reactions like Tiffeneau-Demjanov rearrangement. It is also known for its stable and safe properties, making it a preferred choice in various chemical reactions.

Uses

(TRIMETHYLSYL)DIAZOMETHANE is used as a one-carbon homologation reagent for various applications in the chemical and pharmaceutical industries. It participates in synthesis reactions, including insertion reactions, ketenylations, preparation of homoallylic sulfides, pericyclic reactions, and as a [C-N-N] 1,3-dipole for the preparation of azoles.
Used in Pharmaceutical Industry:
(TRIMETHYLSYL)DIAZOMETHANE is used as a reactant for the preparation of various compounds with potential therapeutic applications. These include:
1. Macrolactam analogs of the natural product macrolide (-)-A26771B, which exhibit improved metabolic stability and antibacterial activity.
2. Aigialomycin D analogues, which act as protein kinase inhibitors for cancer treatment.
3. Unnatural α-amino acid derivatives containing gem-bisphosphonates, synthesized via Michael addition reaction.
4. Capped 4-methylumbelliferyl hyaluronan disaccharides and tetrasaccharides, which serve as potential hyaluronidase substrates.
5. Stictamides A-C, which are matrix metallopeptidase 12 (MMP12) inhibitors with antitumor invasion activity.
6. Endothelin converting enzyme (ECE) Inhibitors WS 75624A and WS 75624B, prepared via a cross-metathesis approach.
7. Ent-kaurene derivatives, which function as anti-inflammatory agents.
8. Desmosdumotin C analogs, potent antitumor agents that act via the activation of the spindle assembly checkpoint.
9. Imidazolo[2,1-b]benzothiazole derivatives, which have potential as p53 inhibitors.
Used in Analytical Chemistry:
(TRIMETHYLSYL)DIAZOMETHANE is used as an analyte in the determination of some phenolic organohalogens in human serum by Gas Chromatography-Mass Spectrometry (GC-MS).
Physical Properties:
(TRIMETHYLSYL)DIAZOMETHANE has a boiling point of 96 °C at 775 mmHg and a refractive index (nD/25) of 1.4362.

Preparation

Trimethylsilyldiazomethane is prepared by the diazo-transfer reaction of trimethylsilylmethylmagnesium chloride with diphenyl phosphorazidate (DPPA) (eq 1).

InChI:InChI=1/C4H10N2Si/c1-7(2,3)4-6-5/h4H,1-3H3

Synthetic route

(N-nitroso-N-trimethylsilylmethyl)acetamide (59546-83-7) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With phenethylamine under 8 - 10 Torr;	95%
With phenethylamine at 40℃; under 14 Torr;

diphenyl phosphoryl azide (26386-88-9) + Chloromethyltrimethylsilane (2344-80-1) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
Stage #1: Chloromethyltrimethylsilane With magnesium; ethylene dibromide In diethyl ether at 40℃; for 1h; Stage #2: diphenyl phosphoryl azide In diethyl ether at 0℃; for 2h;	79%

diphenyl phosphoryl azide (26386-88-9) + (trimethylsilyl)methylmagnesium chloride (13170-43-9) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
In diethyl ether for 16h; cooling;	78%

diazomethane (186581-53-3, 908094-01-9) + trimethylsilyl trifluoromethanesulfonate (27607-77-8) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In diethyl ether 1.) -78 deg C, 2.) 0 deg C;	74%

Chloromethyltrimethylsilane (2344-80-1) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
Stage #1: Chloromethyltrimethylsilane With lithium In diethyl ether at -23 - 20℃; for 2h; Inert atmosphere; Stage #2: With 4-toluenesulfonyl azide In diethyl ether at 0 - 20℃; for 22h; Inert atmosphere;	40%
With diphenyl phosphoryl azide; magnesium 1) diethyl ether, room temp., 2) diethyl ether or dibutyl ether, 0 deg C to room temp.; Multistep reaction;

N-nitroso-N-trimethylsilylmethylurea (39482-21-8) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With potassium hydroxide In benzene	28.2%
With potassium hydroxide In benzene
With potassium hydroxide
With potassium hydroxide In pentane at 0℃; for 1.5h;

Methyl-nitroso-(trimethylsilylmethyl)carbamat (26205-77-6) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With sodium hydroxide

[N-(trimethylsilyl)methyl]urea (5663-03-6) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With hydroxide; cis-nitrous acid Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + trimethylsilyl trifluoromethanesulfonate (27607-77-8) → Hexamethyldisiloxane (107-46-0) + diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In diethyl ether at -78℃; for 2h;

diphenyl phosphoryl azide (26386-88-9) + Chloromethyltrimethylsilane (2344-80-1) → Hexamethyldisiloxane (107-46-0) + diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With magnesium In diethyl ether 2h, 0 deg C -> 3h, r.t.;	A n/a B 8.2 g

N-trimethylsilylmethylamine (18166-02-4) → diazomethyl-trimethyl-silane (18107-18-1)

Conditions	Yield
With 4-nitro-phenol; propane-1,3-diyl dinitrite In 2-methyltetrahydrofuran at 80℃; for 0.333333h; Solvent; Reagent/catalyst; Temperature; Reflux;

Upstream product

• 5663-03-6 [N-(trimethylsilyl)methyl]urea 
• 186581-53-3 diazomethane 
• 27607-77-8 trimethylsilyl trifluoromethanesulfonate 
• 26386-88-9 diphenyl phosphoryl azide 
• 2344-80-1 Chloromethyltrimethylsilane 
• 13170-43-9 (trimethylsilyl)methylmagnesium chloride 
• 59546-83-7 (N-nitroso-N-trimethylsilylmethyl)acetamide 
• 39482-21-8 N-trimethylsilylmethyl-N-nitrosourea 
• 26205-77-6 Methyl-nitroso-(trimethylsilylmethyl)carbamat 
• 18166-02-4 N-trimethylsilylmethylamine 

Downstream Products

• 2550-26-7 4-Phenyl-2-butanone 
• 58416-23-2 benzyl thiophene-2-acetate 
• 121876-51-5 5-Benzhydryl-1-(4-bromo-phenyl)-4-trimethylsilanyl-1H-[1,2,3]triazole 
• 16037-44-8 4-phenyl-3-trimethylsilylpyrazole 
• 89864-99-3 4-trans-styryl-5-trimethylsilyl-1,2,3-triazole 
• 89864-98-2 (E)-5-cyano-4-phenyl-3-trimethylsilyl-2-pyrazoline 
• 451-40-1 phenyl benzyl ketone 
• 112-12-9 methyl nonyl ketone 
• 84655-24-3 1-(4-Chloro-phenyl)-2-(5-trimethylsilanyl-tetrazol-2-yl)-ethanone 
• 484-17-3 9-Phenanthrol 
• 5085-74-5 9-methoxyphenanthrene 
• 21571-63-1 9-Ethoxyphenanthrene 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 1534-27-6 3-dodecanone 

Relevant articles and documents

METALLORGANISCHE DIAZOALKANE XVI. SYNTHESE VON SILYLDIAZOALKANEN Me3Si(LnM)CN2

Silyldiazoalkanes Me3Si(LnM)CN2 (LnM = Me3Ge, Me3Sn, Me3Pb; Me2As, Me2Sb, Me2Bi) have been synthesized by three different routes: (a) reactions of Me3SiCHN2 with metal amides LnMNR1R2 of Group IVB and VB elements, using Me3SnCl as ca

Catalytic trimerization of bis-silylated diazomethane

(Me3Si)2CNN isomerizes upon addition of traces of [Me3Si]+ ions to give (Me3Si)2NNC, which then undergoes an unusual trimerization reaction to give exclusively 4-diazenyl-3-hydrazinylpyrazo

Trimethylsilyldiazomethane - A mild and efficient reagent for the methylation of carboxylic acids and alcohols in natural products

Esterification of various naturally occurring carboxylic acids with trimethylsilyldiazo-methane proceeds nearly quantitatively under very mild conditions. Furthermore, highly sterically hindered alcohols can be converted directly to the corresponding methyl ethers. Improved methods for the preparation and quantification of this reagent are described. Springer-Verlag 2004.