3-Bromopropionyl Isocyanate

[18926-24-4]  · C4H4BrNO2  · 3-Bromopropionyl Isocyanate  · (MW 177.99)

(derivatizing agent for alcohols,1 phenols,2 and arylamines;3 brominating agent potentially present in N-bromosuccinimide brominations;4 bifunctional cyclization reagent5)

Alternate Name: 3-bromopropanoyl isocyanate.

Physical Data: volatile liquid.

Solubility: sol chlorinated, aromatic, and ethereal solvents; reacts violently with H2O, and with basic and protic solvents.

Form Supplied in: prepared from N-Bromosuccinimide as needed.6

Handling, Storage, and Precautions: lachrymator; corrosive; use only in a fume hood; wear protective gloves and preferably a NIOSH-approved respirator. All transfers and reactions should be carried out under anhydrous conditions. Store in a cool dry place, taking care to avoid contamination with protic, basic, or organometallic materials, as these may induce polymerization. Toxicity data for isocyanates are available.7

Derivatization of Alcohols, Phenols, and Amines.

Like other isocyanates, 3-bromopropionyl isocyanate reacts rapidly with N- or O-nucleophiles to give urea and carbamate derivatives, respectively (eq 1).8 Crystalline materials are obtained from primary and unhindered secondary alcohols, while tertiary alcohols give alkenes via elimination.1 Phenols react extremely well, except those containing multiple nitro groups.2 Anilines afford ureas, unless hindered or containing more than one amino group.3 Aliphatic amines usually cause elimination of HBr from the isocyanate, thus yielding N-acryloylurea impurities.3 Note that the presence of the Br atom in these derivatives simplifies crystal structure determination by heavy atom methods.

Isomeric Brominating Agent Present in N-Bromosuccinimide Reactions.

Much recent interest in elucidating the exact nature of the radical chain carriers in N-bromosuccinimide reactions (p-versus s-centered radicals)9 and their respective chemoselectivities has led in turn to a greater understanding of the radical chemistry of 3-bromopropionyl isocyanate. Indeed, radical scavengers form adducts with 3-bromopropionyl isocyanate in several solvents.4,10 The current status of the debate holds that the rate of intramolecular cyclization of 3-bromopropionyl isocyanate (3.7 × 106 at 328 K) is more consistent with a s-centered radical (eq 2).11

Bifunctional Cyclization Reagent.

This molecule contains two reactive centers (isocyanate and bromide) of appreciably different reactivity. Thus far, this relationship has been exploited in the preparation of dihydrouracil antibacterial agents (eq 3).5 It must also be noted that the bromine substituent may be eliminated to give an acryloyl moiety,3 which may give additional modes of reactivity.

1. Johnson, H. W., Jr.; Schweitzer, M. JOC 1961, 26, 3666.
2. Johnson, H. W., Jr.; Day, R. J.; Tinti, D. S. JOC 1963, 28, 1416.
3. Johnson, H. W., Jr.; Kreyssler, H. A.; Needles, H. L. JOC 1960, 25, 279.
4. Tanner, D.; Reed, D. W.; Tan, S. L.; Meintzer, C. P.; Walling, C.; Sopchitz, A. JACS 1985, 107, 6576.
5. Islip, P. J.; Johnson, M. R. JMC 1973, 16, 1308.
6. Johnson, H. W., Jr.; Bublitz, D. E. JACS 1957, 79, 753.
7. (a) Karol, M. H. CRC Crit. Rev. Toxicol. 1986, 16, 349. (b) Henderson, R. ACS Symp. Ser. 1981, 172, 87.
8. (a) The Chemistry of Cyanates and Their Thio Derivatives; Patai, S., Ed.; Wiley: New York, 1977; Part 2, pp 742-755. (b) Findeisen, K.; Konig, K.; Sundermann, R. MOC 1983, E4, 738.
9. (a) Walling, C.; El-Taliawi, G. M.; Zhao, C. JACS 1983, 105, 5119. (b) Skell, P. S.; Tlumak, R. L.; Seshadri, S. JACS 1983, 105, 5125. (c) Tlumak, R. L.; Day, J. C.; Slanga, J. P.; Stiell, P. S. JACS 1982, 104, 7257.
10. Tanner, D. D.; Meintzer, C. P. JACS 1985, 107, 6584.
11. Kaushal, P.; Roberts, B. P. JCS(P2) 1989, 1559.

Erik P. Johnson

Ciba-Geigy Corporation, Summit, NJ, USA

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