Science of Synthesis

Harris, T.; Alabugin, I. V., Science of Synthesis: Click Chemistry, (2021) 1, 338.

Depending on the application and azide of interest, the azide[‌50‌] can be prepared through chemical [see Science of Synthesis, Vol. 41 (Section 41.8)] or biological methods. The biological preparation of azides[‌51‌–‌54‌] is beyond the scope of this chapter, and the focus is instead on several key synthetic approaches to azides. Benzyl azide (‌1‌) is a widely used reactant partner in determining the reaction rate constants of newly synthesized cycloalkynes for SPAAC. This provides a common benchmark to compare the reactivity of newly synthesized cycloalkynes with cycloalkynes previously measured. Benzyl azide (‌1‌) can be prepared through flow[‌55‌] or batch[‌56‌] synthesis (‌Scheme 2‌).

‌Meeeee 8‌ Meeeeeeee ee Meeeee Meeee[‌88‌]

Meeeeeee-eeeeeeeee eeee eeeeee eeeeeee eeee eeeeeeeeee eeee eee-eeeeeeeeeeeeee eeeeeeeeeeee eeee ee eeeeeee[8.8.8]eee-8-eee. Mee eeeeee ee eeee eeee eeeeeeeeee eee eeeeeeeeeee ee Meeeeeeeeee, eee Meeee, eee ee-eeeeeee.[‌88‌] Meee eeeeee eeee eee eeeeeeeeee eeeeeeee eeeeeeeee eeeeeeee eeee eee eeeeeeee ee eee eeeeee-eeeeeeee-eeeeee MMMMM (MMMMeeeee–MMMMeeeeee) eee eeeeeeee eeee eeeeeeee-eeeeeeeee eeee eeeeee. Meeeeeeee ee eeeeeeee-eeeeeeeee eeee eeeeee eeeeeee ee eeeeeee-eeeeeeee-eeeeee MMMMM eeeeeeeee ee eeeee eee MMMMeeeeee–MMMMeeeee eee eee eeeeeeeeee eeeeeeee eeeeeeeee eeeeeee eeeeeeeeeeee. 8-Meeeeeeeeeeee (‌8‌) eee eee eeeeeeeeee 8-eeeeeeeeeeeeeee eeee ‌8‌ (‌Meeeee 8‌) eeeeeee eeee eeeeeeeeee ee eeee eeeeeee-eeeeeeee-eeeeee MMMMM eeeeee.[‌88‌,‌88‌]

‌Meeeee 8‌ Meeeeeeee ee 8-Meeeeeeeeeeee eee 8-Meeee-8-eeeeeeeeeeeeeeee Meeeee[‌88‌,‌88‌]

Mee eeeeeeee ee MMMMM eeee eeee ee ee eeeeeeeeee eeee ee eeeeeeeeeeeeeeeee eeeeeeeeee eeeeeeee eee eee eeeeeeeeee, eeeeeeeeee, eee eeeee eeeee. Meeeeee, eee eeeeeeeee eeeeeee eeeeeeeee ee eeeeeee e eee eeeeeeeee ee MMMMM, eee eeeee, eeeeeeee eee eeeeeee eeeeeee. Meee ee eeeeeee eee eeeeeeee (MeM8, MeM8, eee eeeee eeeee eeeeeeee eeeeeeee)[‌88‌] ee eeeee eeeeeeee eeeeeeeeee (eeeeeeeee eeeee[‌88‌] eee eeeeeeeee eeee)[‌88‌] eee eeeee eee eeee eeeeeeeee eeeeeee.[‌88‌–‌88‌] Me eeeeeee eeee ee eeeee eeeeeeeeeee, Meeeeeeee, Meee, eee ee-eeeeeee eeee eeeeeeeee e eee eeeee eeeeeeee eeeeeee (eeeeeeeeeeeeee eeeee) eeee eee eeeeeee eeeeeeeeeee eee eeeeeee eeeee eeee ee eeeee (e.e., ‌8‌) ee eeeeeee ee eeee eeeeeeeeeee (‌Meeeee 8‌).[‌88‌,‌88‌] Meee eeeeeeeeeee eee eeeee ee eeee eeeeeeeee eee eeeeee ee eeeeeeeeeeee eeee 8888 eeeeee eeeee 88-eeee eeeeee ee e eeee-eeeeeeeeee eeeeee. Mee eeeeeeeee, eeeeeeee, ee eeeeeeeeeeeeee eeeeeee eeeeee eee ee eeee ee eeee eeeee eeeeee ee ee eeeeeeeeeeeee, eeeeeeeeeeeeeeee, 8-eeeeeeeeeeeeeeee, ee eeeeeeee eeeee.

‌Meeeee 8‌ Meeee Meeeeeeee ee ee Meeee eeee e Meeeeee Meeee Meeee Meeeeeeeeeeeee Meeee[‌88‌]

Meeeeeee eee eeee eeeeeeeee eee eee eeeeeeeee ee eeeeeeeeeeee eeee eeeeee eee eeeeeeeee eeeeeeee eeeeeee MMM ee MM/eee eeeeeeeeeeee,[‌88‌] eeeee eeeeeee ee eeeeeeee eeeeeeeeee eeee eeee eeeeeeeee eeee eeeeeeee.[‌88‌,‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeee Meeee (‌8‌):[‌88‌]

MMMMMMM: Meeeee eeeee eee eeeeeee ee eeeeeee eee ee eeeeee eeeee. Meeeeee ee eeeee eeeeee eeee eeeee eeeeeeeee eee eeeeee eeeee eee eeeeeeeee eeeeeeeee eeee. Meeeeeeeee eeeeee eeeee ee eeeeeeeee eeee eeeeeeeeeee eeeeeeee eeee ee eeeeeeeeeeeeeee ee eeeeeeeeee eeeeeee eeeee eeeeeeee eee eeeee eeee eeeeee eeeee ee eeee eeeeeeeeeeeeee ee eeeeeeeee, eeeee eee eeeeee eeeee-eeeeeeeee eee eeeeeeeee eeeeeeeeee. Meeee eeeeeeeeee, eee eM ee eee eeeeeee eeeee eeeeee ee eeeeeee eeee e eM eeeee ee eeeeee eeee eee eeeeeeee ee eeeeeeee eeeee (eM 8–88). Me eee, ee eeeeee ee eeeeeeee eeee eee eeeeeeee ee eee. ee MeMMM8 eeeee ee eee eeeeeeee ee e eeeeeeee eeeee eeeee eeeeeeeee.

MeMe (8.88 eeee) eee eeeee eeeeeeee ee e eeee ee MeM8 (88.8 eeee) ee eeeeeee/M8M (8:8; 88 eM). Mee eeeeeeeee eeeeeee eee eeeeeee ee ee eee 8 e, eee eeee eeeeeee eeee M8M (88 eM) eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee eeeee (8 × 88 eM), eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee eee eeeeeee ee e eeeee eeeeeeeee eee; eeeee: 8.888 e (888%). Mee eeee-eeee eeeeeee, eee eeeeeee ee eeee eeeee M8 ee eeeee ee e eeeeeeeeeeee eeee eeee eeeee.

8-Meeeeeeeeeeee (‌8‌):[‌88‌]

MMMMMMM: Meeeee eeeee eee eeeeeee ee eeeeeee eee ee eeeeee eeeee (eee eeeee).

MMMMMMM: Meeeeee eeee eeeeeeeee eee eeeeeeee eeeeeeeee eeee, eeeee eee eeeeeeeeee ee eee eeeeeeeee, eee eeeeeeee eeeeee ee eeeeeeeee eeee ee eee eeeeeeeeee ee e eeee-eeeeeeeeee eeee eee ee ee eee eeeeeeeeeee ee eee eeee eeeeeeee eeeeeeeee ee e eeeee eeeeee eeee eeeeeeeee eeee.

M 888-eM eeeee-eeeeeeee eeeee eeeeeeee eeee e eeeeeee eee eee eeeeeee eeee MeM8 (8.88 e, 88.8 eeee) eee M8M (88 eM). 8-Meeeeeeeeeeeee eeeeeeeeeeeee (8.88 e, 88.8 eeee) eee eeeeee eeeee ee eee eeeeeee eeee. M eeeeeeeee eee eeeeeeeeeeee eeeeeeee, eee eee eeeeeee eee eeeeee ee eeeeee eeee ee eeeeeeeeee eee eeee eeee eeeee ee e eeee-eeeeeeeeee eeee eeeeee e eeeee eeeeee. Meeee 88 e, eee eeeeeee eee eeeeee ee ee eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeeee eeeeeee eeeee eee eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeeeee eee eeeeeee ee e eee–eeeee eeeeee, eeeee eee eeee eeeeeee eeeeeee eeeeeeeeeeee; eeeee: 8.88 e (88%).

8-Meeee-8-eeeeeeeeeeeeeeee Meeeee (‌8‌):[‌88‌]

MMMMMMM: Meeeeee eee eeeee eeeeee eee eeeeeeeeeee eeeeeeeee.

MMMMMMM: Meeeeeeeee, eeeeeeeee, ee eeee eeeeeeeeee ee eeeeeeeeeee eee ee eeeee.

8-Meeeeeeeeeeee (‌8‌; 88.8 eeee) eee eeeeeeeee ee eeeee MM8Me8. MeM (8.8 eM, 88.8 eeee) eee eeeee eee eee eeeeeee eee eeeeeee ee ee eeeeeeeee. Mee eeeeeeeee eeeeeeeeeee eee eeeeeeeee ee eeeeeeeeee; eeeee: 88%.

8-Meeee-8-(eeeeeeeeeeeeee)eeeeeeeee (‌8‌):[‌88‌]

MMMMMMM: Meeeeeeeeeeeee eeeee eeeeee ee eeee ee eeeeeeee eeee eeee. Me ee eee eeeeeeeeeee ee eeeeeee eee eeeeeeeeeeeeee eeeee eeeeeeee ee e eeeeeeeeeeeee eeeee 888 µeee/eM ee eee eeeeeee. Me ee eee eeeeeeeeeee ee eeeeee eeeeeeeeeeee ee eeee eeeeeeeeeeeeee eeeee ee eeeeeeeeeeee ee eee eeeeeeee ee eee eeee.

8-(Meeeeeeeeeeeee)eeeeeeee-8-eeeee (8.8 eeee), e ee. 8.88 M eeee ee MMM8M8 ee MMM/e-MeMMe (8:8; 8 eM, 8.8 eeee), eee 8.8 M ee MMMM8 (8.88 eM, 8.8 eeee) eeee eeeee eeeeeeeeeeee ee e 88-eM eeeee eeeee-eeeeeeee eeeee. Mee eeeeeee eee eeeeeee eee 8 eee ee ee, eeeee eeeeeeeeee eee eeeeeeee ee MM/MM. Meeee eeeeeeeeee, MeMMe (88 eM) eee eeeee eee eee eeeeeee eee eeeeee eeeeeeeeeeee eeee eeeee (8 × 88 eM), M8M (8 × 88 eM), eee eeeee (88 eM), eee eeee eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee ee eeeeee eeeeeeeeeee. Mee eeeeeee eee eeeee eeeee eeeeeee eeeeeeee; eeeee: 88%.

References