Chloromethyl pivalate

Description

Chloromethyl pivalate (CP) is an electrolyte solvent used in novel lithium-oxygen (Li-O₂) batteries. As the structure of CP does not contain any α-H atoms, CP-based electrolytes exhibit excellent chemical stability in both superoxide radical solutions and the actual Li-O₂ battery environment, effectively resisting the corrosive effects of superoxide radicals. Furthermore, even without the use of a catalyst in the cathode of the Li-O₂ battery, the battery demonstrates high specific capacity and good cycling stability^[6].

Chemical Properties

Clear colorless to slightly yellow liquid

Uses

Chloromethyl pivalate was used in the synthesis of pivaloyloxy methyl ester of ofloxacin as prodrug. It was used as the reagent during the synthesis of an isoindoline-annulated, tricyclic sultam library via microwave-assisted, continuous-flow organic synthesis.

Application

Chloromethyl pivalate is a pharmaceutical intermediate compound used in the synthesis of active pharmaceutical ingredients. It is also involved in the acylation reaction with 9-(2-phosphonomethoxyethyl)adenine. It is used as a protecting agent for the N-protection of amines. It is also used in the preparation of thivaloyloxymethyl ester of ofloxacin as a prodrug. It is also used in the preparation of sulbactam pivoxil by reaction with the sodium salt of sulbactam. Besides, it is used as a reagent in the synthesis of isoindoline cyclic and continuous flow organic synthesis.

General Description

Chloromethyl pivalate reacts with sodium salt of sulbactam to yield sulbactam pivoxil. It undergoes acylation reaction with 9-(2-phosphonylmethoxyethyl)adenine (PMEA) to yield bis(pivaloyloxymethyl) PMEA.

Synthesis

Chloromethyl pivalate is prepared by the reaction of formaldehyd and pivaloyl chloride. The specific synthesis steps are as follows:
A mixture of pivaloyl chloride (8.56 g, 71 mmol), paraformaldehyde (2.13 g, 71 mmol) and zinc chloride (75 mg, 0.55 mmol) was stirred at 80 °C for 2 h. Purification by vacuum distillation afforded chloromethyl pivalate (41) as a colourless oil (6.29 g, 44.7 mmol, 59%). bp 80 °C/15 mmHg [lit.1 bp 80-81 °C/15 mmHg]; 1H NMR (400 MHz, CDCl3) δ 1.24 (9H, s, tBu), 5.72 (2H, s, CH2).

References

[1] Synthetic Communications,  1995,  vol. 25,  # 18,  p. 2739 - 2749
[2] Bioorganic and Medicinal Chemistry,  2012,  vol. 20,  # 13,  p. 3997 - 4011
[3] Patent: WO2013/133726,  2013,  A1. Location in patent: Page/Page column 76
[4] Tetrahedron Letters,  1989,  vol. 30,  # 51,  p. 7141 - 7144
[5] Journal of Pharmaceutical Sciences,  1994,  vol. 83,  # 9,  p. 1269 - 1273
[6] Taoran Li . (2017). Chloromethyl pivalate based electrolyte for non-aqueous lithium oxygen batteries. Chinese Chemical Letters, 28 11, Pages 2155-2158. https://doi.org/10.1016/j.cclet.2017.09.021