Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 30.

The Japp–Klingemann reaction[‌163‌] is a method for the formation of monoarylhydrazones of 1,2-diketones[‌99‌] or α-oxo esters. Careful hydrolysis of a β-oxo ester, e.g. ‌97‌, produces the corresponding acid ‌98‌ the enol of which is reacted with an arenediazonium salt giving an arylazo derivative ‌99‌. Subsequent loss of carbon dioxide (perhaps as shown by the arrows on ‌99‌), gives the monoarylhydrazone ‌100‌ of a 1,2-diketone, indolization of which produces a 2-acylindole ‌101‌ as exemplified in ‌Scheme 37‌.[‌164‌]

‌Meeeee 88‌ Meee–Meeeeeeeee Meeeeeee eee Meeeeeeeee Meeeeee Meeeee Meeeeeeee Meeeeeeeeee ee Meeeeeeee ee 8-(8-Meeeeeeeeeeeeee)-8M-eeeeee[‌888‌]

Meee eee eeeeeee ee eeeeeee ee β-eee eeeeee, eeeeeeee ee eee eeee eeeeeee eeeee ee eee eeeeeeeeeeeee ee e eeeeeeee, eeeeeeeeeeee ee eeeee eeeeeeee ee eeeeee-8-eeeeeeeeeee.[‌888‌,‌888‌] M eeeeeeeee eeeeeeeee ee 8-eeeeeeeeeeeeeeeeee[‌888‌] (eeeee eee ee eeeeeeeeeeeeee ee eeeeeee eeeeeeeeeee) eeeeeeee eeee eeeeeeeee.

Meeeeeeeeee ee eee eeeeeeeee ee eeeee 8-eeeeeeeeeeeeeeeeeeeeeeeeee (‌888‌) eeeee eeeeeeeeeeeeeeee eeee ‌888‌, eeeeeeeee ‌888‌, eeeee eeee ee eeeeeee eee eeee eeeeee eee eeeeeee Meeeeee eeeeeeee ee eee 8,8-eeeeeeeeee eeee, eeee eeeeee ‌888‌, eeeee ee eeee eeeeeeeee ee ‌888‌ (‌Meeeee 88‌).[‌888‌] Mee eeeeeeeee eeee eeeeeee ee 8-(eeeeeeeee)eeeeeee eee eeeee 8-eeeeee-8-(8,8-eeeee-8,8-eeeeeee-8M-eeeeeeee-8-ee)eeeeeeeeee (‌888‌) eeeeeeee eeeeee ‌888‌ (‌Meeeee 88‌);[‌888‌] eee 8-eeeeeee eeeeeeee eee ee eeeeeeeeee eeeeeeee ee 88% eeeee eeee 8-eeeeeeeeeeeeeeeeeeeeeee eeeeeeee eee eeeeeeeeee ee 8-eeeeeeeeeeeeeeeee ee 88% eeeee.[‌888‌] Meeeeeeeeeeee, ee ee eeeeeeee ee eeeeeeee ee eeeeeeeeeee eeeeeeee ee eee eeeeeeeeeeee eeeeeeee; eeeeeeeeeeeeeeeeee ee eeeeeeeeeeee-8,8-eeeee eee eeeeeeeeeee-8,8-eeeee ‌888‌ eee ee eeee eeeeeeee eee Meeeeee eeeeeeee ee eeee eeeeeeeee eeeeeee eeeeeee ‌888‌ (‌Meeeee 88‌). Me eeeee eeeeeeeee, eee eeeeeeeee ee eeeeeeeeee eee eee β-eeee eeeee ee eeeeeee eeeeeeeeee eeee eeeeee eeeeeeeee eeeee ee eeeeee eeee eee eeeeeeeee eeeeeeee.[‌888‌]

‌Meeeee 88‌ Meee–Meeeeeeeee Meeeee Meeeeeeee eeee e Meeeee β-Mee Meeee[‌888‌] eee ee Meeeeee β-Mee Meeee[‌888‌]

‌Meeeee 88‌ Meee–Meeeeeeeee Meeeeeeee ee 8-Meeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

Meeeeeeee ee eeeeeeeeee eeeeee ee eee Meee–Meeeeeeeee eeeeeeee ee eeee eeeeeeeeeee ee eee eeeeeeeeeee ee eeeee 8-eeeeee-8-(eeeeeeeeeeeeeee)-8M-eeeee-8-eeeeeeeeeeeee (‌888‌) eeeeeeee eeee eeeeeeeeee 8-eeeee-8-eeeeeeeeeeeee eeee eee eeeee 8-eeeeee-8-eeeeeeeeeeee (eeeee ee eeeeeeeeee eeee eeeeee eeeeeeee eeeee ee eeeeeeee ee eee eeeeeeeee eeeeeeee); eeee, ee ee eee eeeeee eeee eeeee ee eeee eee e eeeeeee Meeeeee eeee eeeeeee ee eeeeeeeeeeeee ‌888‌ (‌Meeeee 88‌); eee eeeeeeee eeeeeeeeeeee ee eeeeeeee eee eeeeeee eeeeee ee eee eeeeee, e.e. eeeee 8-eeeeee-8-(eeeeeeeeeeeeeee)-8M-eeeee-8-eeeeeeeeeeeee, ee eeeeeeee eeeee eeeeeeeeee 8-eeeee-8-eeeeee-8-eeeeeeeeeee eeee, eeeeeeeeee Meeeeee eeeeeeeeeee eeeee ee eee eeeeeeee, eeee eeeeeeeeee eeeeeeeeeeeeee eeeeeee ee eee eeeeee.[‌888‌]

Mee Meee–Meeeeeeeee eeeeeeee eee eeee ee eeeeeeee eeeee e eeeeeeee (ee e eeeeeeeeeee Meeeeee’e eeee) eeee, eee eeeeeee, eeeeeeee ee 8-eeeeeeeeeeeeeeeeeeeeeee eeeeeeee eeee eeeeeee eeeeeeeeeeeeee eeeeeeee eee-eeeeeeee ‌888‌, eeeee ee eeee eeeeeeeee eeee eeeee 8-eeeeeee-8M-eeeee-8-eeeeeeeeeeeee ‌888‌ (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meee–Meeeeeeeee Meeeeeeee ee Meeeee-8-eeeeeeeeeeee[‌888‌]

‌Meeeee 88‌ Meee–Meeeeeeeee Meeeeeeee Meeee Meeeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

8-(8-Meeeeeeeeeeeeee)-8M-eeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

Meeeee 8-eeeeee-8-eee-8-(8-eeeeeee)eeeeeeeeee (‌88‌; 888 ee, 8.8 eeee) eee eeeeeee eeee MeMM (888 ee, 8.8 eeee) ee M8M (8 eM) eee MeMM (8.8 eM) ee ee eee 88 e. Mee eeeeeee eee eeeeee ee 8°M, eee (88 e) eee MeMMe (888 ee) eeee eeeee, eee eee eeeee eee eeee eeeee, eeee eeeeeeee, ee e eeee ee eeeeeeeeeeeeeeee eeeeeeee [eeeeeee (888 ee, 8.8 eeee), eeeee MMe (8.88 eM), eee MeMM8 (888 ee, 8.8 eeee)]. Meeee 8 e ee 8°M, eee eeeeeee eee eeeeeeeee eeee MeMMe, eee eeeeeee eee eeeee eee eeeeeeeeeeee, eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeeee) ee eeee 8-(eeeeeeeeeeeeeee)-8-(8-eeeeeee)eeeeee-8-eee (‌888‌); eeeee: 888 ee (88%); ee 888–888°M.

8-(Meeeeeeeeeeeeee)-8-(8-eeeeeee)eeeeee-8-eee (‌888‌; 888 ee, 8.8 eeee) eee eeeeee ee eeeeee M8MM8 (8 eM) ee 888°M eee 88 eee. Mee eeeeee eeee eee eeeeeee eeee M8M eee eee eeeeeee eee eeeeeeeee eeee MeMMe. Mee eeeee eeeeeee eee eeeeeeeeeeee eee eeeeeeeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeeee) eeeeee ‌888‌; eeeee: 88 ee (88%); ee 888–888°M.

Meeee 8-(Meeeeeeee)-8-[8-(8,8-eeeee-8,8-eeeeeee-8M-eeeeeeee-8-ee)eeeee]-8M-eeeeee-8-eeeeeeeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

8-(Meeeeeeee)eeeeeee (888 e, 8.88 eee) ee eeeeeeeee MeMM (888 eM) eee eeeeeee eeeeeee eeee e eeeeeee ee eeeee MMe (888 eM) eee M8M (888 eM), eee eeee eee (888 e). MeMM8 (88 e, 8.888 eee) ee M8M (888 eM) eee eeeee ee eee eeeeeee eeeeeeeeee eeee 88 eee eee eee eeeeeeeeee eee eeeeeee eee e eeeeeee 88 eee eeeeeee 8°M eee 88°M. Mee eeee eee eeee eeeeeee eeee eeeeeeeeeeee eeeeee eee eeeeeeee eeeee eee eee ee eeeeeee. Meeee 8-eeeeee-8-(8,8-eeeee-8,8-eeeeeee-8M-eeeeeeee-8-ee)eeeeeeeeee (‌888‌; 888 e, 8.88 eee) eee eeeeeeeee ee eeee MeMM (8888 eM) eee eeee MeMMe (888 e) eee eee (888 e) eeee eeeee ee eee eeeeee eeee. Meee eeeeeee eee eeeeeee ee 8°M eeeee eee eeeeeeee eeeeeeeeee eeee eee eeeee eeeeeee, eee eee eeeee eee eeeeeee eee eeeeeee ee eeee ee ee. Mee eee eee eeee eeeeeeeee eee eeeeeeeee eeee eeeeeee (MMMMMMM: eeeeeeeeee) eee eee eeeeeeee eeee eeeee (Me8MM8) eee eeeeeeeeeeee. Mee eeeeeeeee eeeee eeeeeeeee eee eeeeeeeee ee eeeee MeMM (8888 eM) eee eeee eeee eee eeeeeeeee ee eee eeeeeee eeeee eeee MMe eee. Meeee eeeeeee ee eee, eeeeee ‌888‌ eee eeeeeeeee ee eeeeeeeeee eee eeeee ee 88°M; eeeee: 888 e (88%); ee 888–888°M.

Meeee 8-Meeeee-8-(eeeeeeeeeeeeeee)-8M-eeeee-8-eeeeeeeeeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

Meeeee 8-eeeeee-8-eeeeeeeeeeeee (8 e) ee MeMM (88 eM) eee eeeeee ee <8°M eee eeeee MMe (8 eM) eee eeeee eeeeee. Me eeeeeee eeee ee MeMM8 (8.88 e) eee eeee eeeee eeeeee eee eee eeeeeeeeeee eee eeeeeeeeee ee <8°M eeee eeeeeeee eee 8 e (eeee M). Meeee 8-eeeeee-8-eeeeeeeeeeee (8.8 eM) eee eeeeee eeeee ee eeeeeee eeeeeeee MeMMe [Me (888 ee) eee eeeee MeMM (888 eM)] eee eee eeeeeee eee eeeeeee eee 8.8 e (eeee M). Meee M eee eeeee eeeeee ee eeee M, eee eeee eee eeeeeee eee eeeeeee eee 8 e ee 8–8°M, eeeeee ee M8M (888 eM), eee eeeeeeeee eeee MM8Me8 (8 × 888 eM). Mee eeeee eeeeeee eeeee (Me8MM8) eee eeeeeeeeeeee ee eeee eeeeeeeeeeeee ‌888‌ (88% eeeee). Mee eeeeeeeeeeee, eee eeeeeeeee eee eeeeeeeee ee MeMM, MMe(e)-eeeeeeeee MeMM (88 eM) eee eeeee, eee eee eeeeeee eee eeeeeee eee 88 eee. Meeeeeeeeeeee eeee e eeeee, eeeee eee eeeeeeeee ee MM8Me8 eee eeeeee ee eeeeeeee eeee eee. ee MeMMM8, M8M, 8.8% MeMM, eee M8M. Mee eeeeeee eeeeeeee eeeee e eeeeeeee eeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/MM8Me8 8:88). Meeeeeeeeeeee ee eeeeeeeeeee eeeeeeeee eeee eee eeeeeee ee e eeeeeeeee eeeee eeeee; eeeee: 88%.

Meeee 8-Meeeeee-8M-eeeee-8-eeeeeeeeeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee MeMM8 (88.8 e, 8888 eeee) ee M8M (888 eM) eee eeeeee eeeee ee e eeee ee e-eeeeeeeee (888.8 e, 8888 eeee) ee eeeee MMe (888 eM, 8888 eeee) eeee eee (8888 e) eeee 88 eee. Mee eeeeeeeeeee eee eeeeeeeeee ee 8°M eee ee eeeeeeeeee 88 eee. Mee eeeeeeeee eeee eeee eee eeeee ee eeeeeeee (88 eee) ee 8°M ee e eeeeeee eeeeeeeeee ee eeeeeee eeeeeeeeeeeeee (888.8 e, 8888 eeee), Me8MM8 (888.8 e, 8888 eeee), eee Me8M (888.8 e, 888 eeee) ee M8M (888 eM) eee MeMM (8888 eM). Meeee 8.8 e ee 8°M, M8M (8888 eM) eee eeeee ee eee eeeee eeeeeeeeee (eM 88.8). Mee eeeeeeeee eeeeeee eee eeeeeeeeeeee (888-eM eeeeeeeeee) eeeee eeeeeee eeeeeeee (88°M/88 Meee) eee eeee eeeeeeeee eeee eeeeeee (8 × 8888 eM), eee eee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee (88°M/88 Meee), eeeeeee eee eeeee eee eeeeeee ‌888‌ ee e eee eee (ee. 888 e) eeee eee eeeeeeeee ee eeee.

Me eee eeeee eee eeeeeee ‌888‌ (888 e) ee MeMM (888 eM) eee eeeee eeeeeeee eeee 88 eee ee 88–88°M e 88% eeee ee MeMMe (88.8 e, 888 eeee). Meeee 88 eee, eeeeeeeee eeeeeeeee eee eeeeeeee (MMM) eee eee eeeeeee eee eeeeee ee eeeeee, eee eeeeeeeeeeeeee, MMe(e) (888 e, 8888 eeee) eee eeeee eeee 8 e. Meeeee eee eeeeeeeeee eee 88 eee eeeee eee eee ee eee eeeeeeee ee MMe. Mee eeeeeee eee eeeeee ee ee, eee M8M (888 eM) eee eeeee. Mee eeeeeee eee eeeeee ee 8°M eee 8.8 e eee eee eeeeeeeee eeeeeeeeee eee eeeeeeee; eee eeeee eee eeeeee eeee eeeeeeeee (8°M) MeMM (8 × 888 eM) eee eeee eeee M8M (8 × 888 eM) eee eeee eeeeeee ee eee ee eeeeeeee, eeeeeee eee eeeee eeeeee eeeee ee e eeeeee eeeeee; eeeee: 888 e (88%; 8 eeeee); ee 888–888°M.

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