Comments on a Conversion of Epoxides to Halohydrins with Elemental Halogen Catalyzed by Phenylhydrazine: Tandem Electrophilic Halogenation of Aromatic Compounds and Epoxide Ring Opening to Halohydrins

Abstract

The halogenation of aromatic compounds by bromine or chlorine in the presence of an epoxide gives the corresponding halogenated aromatics and 2-halohydrins, both with good yields.

Key words

epoxides - halogenation - chlorohydrins - bromohydrins - arenes - bromine

References

• 2 Sharghi H. Eskandari MM. Synthesis  2002,  1519 
• There are two possibilities: electrophilic halogenation of phenylhydrazine, and the oxidation of phenylhydrazine by halogen. Both reactions give hydrogen halogenide as a side product. Therefore, the reaction of arylhydrazines with chlorine or bromine gave a mixture of chlorination/bromination and oxidation products, mainly aryldiazonium salts, and the products thereof. We found some precedents in the literature. For examples, see:
• 4a Chattaway FD. Hodgson GD. J. Chem. Soc.  1916,  583 
• 4b Chattaway FD. J. Chem. Soc.  1908,  852 
• 4c Chattaway FD. J. Chem. Soc.  1909,  862 
• 4d Michaelis L. Ber. Dtsch. Chem. Ges.  1893,  26:  2190 
• 4e Vaubel W. J. Prakt. Chem.  1894,  49:  540 
• The oxidation of arylhydrazines to diazonium salts by bromine were exploited as a preparative way for substitution of the NHNH₂ moiety by bromine. For examples, see:
• 5a Callander DD. Coe PL. Tatlow JC. Tetrahedron  1966,  22:  419 
• 5b Field LD. Hambley TW. Pierens GK. Tetrahedron  1990,  46:  7069 
• 5c Joshi SS. Deorha DS. J. Chem. Soc.  1957,  2414 
• The substitution of the NHNH₂ moiety by iodine was described by Joshi,^5c as well as by:
• 6a Brady OL. Bowman JH. J. Chem. Soc.  1921,  119:  896 
• 6b Meyer E. J. Prakt. Chem.  1887,  36:  115 
• Also, the application of halogens for the oxidation of N,N′-disubstituted hydrazines to azo compounds is a well-documented fact. See for example:
• 7a Overberger CG. Pao-Tung H. Berenbaum MB. Org. Synth. Coll. Vol. IV   Wiley; London: 1966.  p.66 
• 7b Rabjohn N. Org. Synth. Coll. Vol. III   Wiley; London: 1966.  p.375 
• There are many examples of using epoxides as hydrogen halogenide scavengers or a specific kind of ‘terminating’ base. The side products of those reactions are usually halohydrins. For example, epoxides were extensively used for the precipitation of amino acids from their hydrochlorides or hydrobromides, see:
• 10a Gmeiner P. Feldman PL. Chu-Moyer MY. Rapoport H. J. Org. Chem.  1990,  55:  3068 
• 10b Jackson RFW. Turner D. Block MH. J. Chem. Soc., Chem. Commun.  1995,  2207 
• 10c Chambers JR. Isbell AF. J. Org. Chem.  1964,  29:  832 
• For other, more sophisticated examples, see:
• 11a Sato K. Kojima Y. Sato H. J. Org. Chem.  1970,  35:  2374 
• 11b Isaacs NS. Kirkpatrick D. Tetrahedron Lett.  1972,  3869 
• 11c Hartshorn MP. Jones ERH. J. Chem. Soc.  1962,  1312 
• 11d Kirk DN. Patel DK. Petrow V. J. Chem. Soc.  1956,  627 
• 11e Hunsberger IM. Tien JM. Chem. Ind.  1959,  88 
• 11f Buddrus J. Angew. Chem., Int. Ed. Engl.  1968,  7:  536 ; Angew. Chem. 1968, 80, 535
• 11g Buddrus J. Angew. Chem., Int. Ed. Engl.  1972,  11:  1041 ; Angew. Chem. 1972, 84, 1173
• 11h Weyerstahl P. Klamann D. Finger C. Nerdel F. Buddrus J. Chem. Ber.  1967,  100:  1858 
• 13a Organikum   Fichte B. VEB Deutscher Verlag der Wissenschaften; Berlin: 1977.  p.384 
• 13b Vogel AI. Textbook of Practical Organic Chemistry   Longman; London: 1978.  p.585 
• 13c Clarke HT. Brethen MR. Org. Synth. Coll. Vol. I   Wiley; London: 1966.  p.121 
• 13d Koelsch CF. Org. Synth. Coll. Vol. III   Wiley; London: 1966.  p.132 
• 13e Barber HJ. Fuller RF. Green MB. J. Appl. Chem.  1953,  3:  409 

1

Since citation of more than 50 papers in this short article is not appropriate, we are ready to send a copy of a text file with the citations to interested readers.

3

For concluding that the phenylhydrazine is a catalyst, it is necessary to find it, or better to isolate it, or much better to use it again, after reaction.

8

Sharghi and Eskandari [2] concluded that 10 mol% of phenylhydrazine is enough to obtain optimum yields of halohydrins. This is inconsistent with the stoichiometry of the total possible bromination and oxidation of phenylhydrazine which could give only eight HBr molecules (PhNHNH₂ + 7 Br₂ = C₆Br₆ + N₂ + 8 HBr). However, we did not observe more than tetrabrominated products in the reaction mixture. Since the main product is 2,4,6-tribromophenylhydrazine, the proper stoichiometry should be at least one mole of phenylhydrazine per three moles of bromine (and respectively 3 mol of epoxide).

9

If our conclusion is correct, Sharghi and Eskandari [2] should observe the same or similar regioselectivity in their reaction as in a common ring opening by hydrogen halogenides. However, some of the results described in Table 2 of ref. [2] are hard to understand, since in many cases the regioselectivities recorded are opposite to those indicated by the mechanism of the ring opening reaction of epoxides and, therefore, should be re-analysed.

12

Since phenylhydrazine is oxidized by iodine into phenyldiazonium iodide and HI as a side product, it is hard to understand the stoichiometry of the reaction described [2] - there are only three molecules of hydrogen iodide per mole of phenylhydrazine (PhNHNH₂ + 2 I₂ = PhN₂ ⁺I^- + 3 HI).