For those wondering if bromosafrole can be used to any advantage, my guess is that this review of the most recent advances in the Gabriel synthesis proves that the answer is an emphatic YES!
Ritters bromosafrole synth:
Post 243189 (https://www.thevespiary.org/talk/index.php?topic=9676.msg24318900#msg24318900)
(Ritter: "Re: Notes on bromination of safrole", Methods Discourse)
and some more details are found on the following page:
https://www.thevespiary.org/rhodium/Rhodium/chemistry/mda.azide.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/mda.azide.html)
Novel Gabriel Reagents
ULF RAGNARSSON* and LEIF GREHN
Acc. Chem. Res., Vol. 24, No. 10, 1991; pp. 285-289
(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_imgs/pdf.gif)
As demonstrated in this review, during the last two decades a considerable number of compounds have been investigated as substitutes for phthalimide or its potassium salt in the Mitsunobu and Gabriel reactions. Their major advantages are 2-fold: Much milder and rather specific conditions can be used for the final deprotection than are required for phthaloyl, and alkylation can, if required, be carried out twice, in which case also secondary amines are obtained. Several of the novel reagents are easily made, and they can be alkylated in the same way as phthalimide or its potassium salt, but neither strong acid or base nor hydrazine is needed to cleave off the protecting group(s). Besides, the approaches described above to prepare imidodicarbonates and acylcarbamates are in principle rather flexible and should, if necessary, allow additional, selectively protected compounds to be made in the same way. Thus, the imide concept as such has withstood the ravages of time since its introduction a century ago. In parallel, much work aimed at the direct alkylation of amides has recently been performed, and in many cases it is now possible to obtain specific, relatively simple amides from which the corresponding amines can be regenerated. Many acyl groups used in this context require, however, cleavage conditions which occasionally cannot be tolerated, and the application of carbamates would probably be a better alternative in such cases.
The Gabriel-Colman Rearrangement in Biological Systems: Design, Synthesis and Biological Evaluation of Phthalimide and Saccharin Derivatives as Potential Mechanism-Based Inhibitors of Human Leukocyte Elastase, Cathepsin G and Proteinase 3
William C. Groutas, Lee S. Chong, Radhika Venkataraman, Jeffrey B. Epp, Rongze Kuang, Nadene Houser-Archield, and John R. Hoidal
Bioorganic & Medicinal Chemistry, Vol. 3, No. 2, pp. 187-193, 1995
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Here are two experimental examples (taken from page 191 of the above citation) of the use of potassium phthalimide and sodium saccharin in the same type of reaction:
2-(1, 3- D i o xo- l,3-dihydro-isoindol-2-ylmethyl)-acrylic acid methyl ester 11
Potassium phthalimide (54 mmol) was added to a solution of ~-(bromomethyl)acrylate (50 mmol) in 50 mL dry DMF. The reaction mixture was stirred at room temperature overnight, poured into 200 mL ice-cold water and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate. The mixture was filtered and the filtrate was evaporated in vacuo, leaving a crude product which was purified by flash chromatography (8.7 g, 71% yield).
2-(1,1,3- Trio xo- l ,3-dihydro-benzo[ d ] isothiazol- 2- ylmethyl)-acrylic acid methyl ester 13
Sodium saccharin (3.0 g, 14.4 mmol) was added to a stirred solution of ¢t-(bromomethyl)acrylate (1.41 g, 7.9 mmol) in 10 mL dry DMF at 0 *C. The reaction mixture was stirred for 10 min at 0 °C, 2 h at room temperature and then poured into ice-cold water. The resulting precipitate was collected and washed with hexane (1.80 g, 81% yield).
The yield from the sodium saccharin example seems to be higher than that of the one using potassium phthalimide; furthermore, the reaction proceeds much quicker with the apparent need of a lower reaction temperature. I wonder why?