Novel Diradical-Mediated Ring Opening Reactions

Abstract

Thermo-isomerization of medium- and large-ring 1-phenylcycloalkanols 1e-i at around 650 °C in a flow reactor system delivers the open-chain phenones 4e-i. A reaction mechanism via an open-chain diradical intermediate, followed by an intramolecular hydrogen transfer is proposed. Thermo-isomerization of α-substituted 1-phenylcyclododecanols 6 proceeds regioselectively under the formation of ω-substituted phenones 7. Furthermore, this novel hydrogen transfer reaction provides a new access to ω-substituted fatty acids.

Key words

thermal ring opening - dynamic gas phase thermo-isomerization - diradical intermediates - radical hydrogen transfer - regioselectivity in homolytic cleavage

References

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• 5a

  Thermo-isomerization reactions were performed in a flow reactor system using a quartz tube (110 cm length, and 3 cm i.d., respectively) heated by a tube furnace (100 cm with 6 different temperature zones, which can be separately adjusted).

• 5b

  Typical procedure: After evacuation of the apparatus with a high-vacuum oil pump, the starting material (0.5-5 g) was directly distilled through the preheated reactor tube (estimated contact times: about 1-2 s). A flow of nitrogen gas was adjusted from 12 mL/min to 24 mL/min (0.8-2.4 L/h). At the end of the reactor unit the isomerization products were collected in a trap, which was cooled with liquid N₂ (90-95% recovery).

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4

1-Phenylcycloalkanols 1 were synthesized from the corresponding cycloalkanones by addition of phenyl lithium or phenyl magnesium bromide according to ref. 9.

7

Deuterium content was determined by mass spectroscopy.

10

Deuterium content was determined by ¹H NMR spectroscopy, chemical shifts were determined by ²H NMR spectroscopy.

11

2,2,12,12,12-d ₅-4g: ¹H NMR (300 MHz, CDCl₃): δ
(ppm) = 7.95 (dt, J = 7.0 Hz, 1.2 Hz, 2 H), 7.55 (tt, J = 7.3 Hz, 1.3 Hz, 1 H), (tt, J = 7.2 Hz, 1.3 Hz, 2 H), 1.72 (t, J = 7.1 Hz, 2 H), 1.59-1.26 (m, 14 H). ¹³C NMR (75 MHz, CDCl₃): δ (ppm) = 200.47 (C), 137.04 (C), 132.71 (CH), 128.42 (CH), 127.95 (CH), 31.71 (CH₂), 29.49 (CH₂), 29.37 (CH₂), 29.27 (CH₂), 29.22 (CH₂), 29.21 (CH₂), 29.20 (CH₂), 24.23 (CH₂), 22.42 (CH₂). IR (CHCl₃): 3063 (vw), 2929 (vs), 2856 (vs), 1679 (s), 1599 (w), 1581 (w), 1467 (w), 1448 (m), 1272 (s)cm^-1. MS m/z (rel intensity) 266 (12), 265 (20), 135 (9), 121 (100), 105 (78).

12

Intermolecular processes can be excluded under DGPTI-conditions.