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

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

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

Downstream Products

• 2612-87-5 1-Trimethylsilyl-2.2-diphenyl-cyclopropan 
• 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 
• 5009-33-6 1-dodecen-11-one 
• 1534-27-6 3-dodecanone 
• 6175-49-1 dodecan-2-one 
• 122053-69-4 (2S,3R)-2-Phenyl-3-trimethylsilanyl-cyclopropane-1,1-dicarbonitrile 
• 84645-40-9 4-Benzyl-5-trimethylsilanyl-1H-[1,2,3]triazole 
• 579-74-8 2-Methoxyacetophenone 
• 102-16-9 benzyl 2-phenylacetate 
• 1015-97-0 (1,4)-Naphthoquinono<3,2-c>-1H-pyrazole 
• 75-97-8 3,3-dimethyl-butan-2-one 

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

Batch and Continuous-Flow One-Pot Processes using Amine Diazotization to Produce Silylated Diazo Reagents

A novel synthesis of trimethylsilyldiazomethane (TMSCHN2) by diazotization of trimethylsilylmethylamine (TMSCH2NH2) is reported using batch and continuous flow synthesis. The latter affords a daily production of 275 g (2.4 mol) of TMSCHN2. Other silylated methylamines were also successfully reacted under the developed reaction conditions to furnish various silicon-bearing diazomethane reagents. The applicability of the process is highlighted by disclosure of batch and continuous flow one-pot esterification and 1,3-dipolar cycloaddition processes. Furthermore, the high-yielding esterification of carboxylic acids with silylated and substituted methylamines in continuous flow is disclosed. Finally, work-up and purification procedures are reported for the preparation of a 2-MeTHF solution of TMSCHN2, which can be used in rhodium-catalyzed methylenation and homologation reactions.

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

Rhodium-catalyzed synthesis of terminal alkenes

Terminal alkenes have been efficiently prepared via a rhodium-catalyzed olefination procedure using Wilkinson's catalyst in the presence of triphenylphosphine, 2-propanol and trimethylsilyldiazomethane. Optimized reaction conditions are described for aldehydes and ketones, as well as alternative work up procedures. Georg Thieme Verlag Stuttgart.

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.

Rearrangement Approaches to Cyclic Skeletons. IV. The Total Synthesis of (+/-)-Pinguisone and (+/-)-Deoxopinguisone Based on Photochemical Acyl Migration of a Bicyclonon-6-en-2-one

The total synthesis of (+/-)-Pinguisone (2) and (/-)-deoxopinguisone (3), fused ring sesquiterpenes, has been achieved starting from 1-methoxy-3,4,5-trimethylbenzene. 1-Methoxy-4,5,endo-8-trimethylbicyclonon-5-en-2-one (9) was prepared selectively via facial selective Diels-Alder reaction of the diene derived from the benzene and 2-chloroacrylonitrile.Ring enlargement of 9 using (CH3)3SiCHN2 and BF3 etherate gave the corresponding bicyclooct-en-2-one (8).The photochemical acyl migration of 8 gave the fused-ring compound (7).The fourth methyl was introduced selectively by the conjugate addition of (CH3)2CuLi to the spironon-8-ene-3,2'-dioxolan>-7-one prepared from 7.Each furan ring of 2 and 3 was constructed via the corresponding butenolide derived from the γ-keto acid by acid-catalyzed dehydration.

Process for preparing trialkylsilyldiazomethanes

A process for preparing trialkylsilyldiazomethanes in which halomethyltrialkylsilane represented by the general formula R1 R2 R3 SiCH2 X (wherein R1, R2 and R3 denote an alkyl gr

A CONVENIENT, HIGH YIELD SYNTHESIS OF TRIMETHYLSILYLDIAZOMETHANE

A new one step synthesis of trimethylsilyldiazomethane is described.

New Methods and Reagents in Organic Synthesis. 28. A Convenient and Efficient Preparation of Trimethylsilyldiazomethane (TMSCHN2) using Diphenyl Phosphoroazidate (DPPA)

The stable and safe compound trimethylsilyldiazomethane (TMSCHN2), which is useful for organic synthesis, was prepared in high yield by diazo-transfer reaction of trimethylsilylmethylmagnesium chloride with diphenyl phosphoroazidate