Practical Alternative Synthesis of 1-(8-Fluoro-naphthalen-1-yl)piperazine

Abstract

Convergent synthesis of 8-fluoronaphthalen-1-ylamine (6) was achieved through the reaction of 1H-naphtho [1,8-de][1,2,3]triazine (15) with HF-pyridine under mild conditions. This new synthesis for the preparation of 6 overcame many scale-up challenges that exist in the methods reported in the literature and provided a practical alternative synthesis of 1-(8-fluoronaphthalen-1-yl) piperazine (1).

Synthesis and Crystallography of 8-Halonaphthalene-1-Carbonitriles and Naphthalene-1,8-Dicarbonitrile

“…The key intermediate triazine 1 (Scheme 1) was prepared [12][13][14] by diazotisation of the commercially available naphthalene-1,8-diamine 15 with isoamyl nitrite in acetic acid and ethanol in 81% yield.…”

“…Elemental analyses were performed at M-H-W Laboratories, Phoenix, AZ. Triazine 1 was prepared by a literature procedure 12 and 1,8-dibromonaphthalene (5) was prepared by a literature procedure. 20 8-Chloronaphthalen-1-amine (2a): 1H-Naphtho[1,8-de][1,2,3]triazine (1, 1.521 g, 9.00 mmol) was mixed with an excess of 36% hydrochloric acid (75 mL).…”

Synthesis and Characterization of Group 4 Fluorinated Bis(amidinates) and Their Reactivity in the Formation of Elastomeric Polypropylene

“…Argon and nitrogen were purified by passage through a MnO oxygen removal a The legends at the spectrum correspond to the different atoms in the corresponding complexes as defined in Figure 11. 4 , Zr(NMe 2 ) 4 , 17 and 8-fluoronaphthalen-1-ylamine 18 were prepared by literature procedures. NMR spectra were recorded on a Bruker Avance 300 spectrometer.…”

Balz-Schiemann Reaction

“…Other fluoro-de-triazenation systems such as TfOH/ CsF [30] and polyphosphoric acid (PPA)/ BF 3 ÁEt 2 O [31] have also been used for this purpose. The fluoro-detriazenation of cyclic triazene 1H-naphtho [1,8-de] [1,2,3]triazine provided a facile access to 1-amino-8fluoronaphthalene in large scale (Scheme 6) [32]. However, the fluoro-detriazenation of acyclic triazenes is often accompanied by the competitive formation of substantial amounts of sideproducts [30,33].…”