Structural properties and Synthesis of 1-Bromo-4-chlorobutane

1-Bromo-4-chlorobutane is an alkyl dihalide compound that exists as a clear and colorless liquid under standard temperature and pressure. It is insoluble in water but miscible with common organic solvents. In organic synthesis, 1-bromo-4-chlorobutane is frequently employed as a bifunctional linear alkane precursor for 1,4-difunctionalization and demonstrates notable utility in fundamental studies of organic synthetic methodology.

Structural properties

Researchers describe a transitiometric method for determining the isobaric thermal expansivity of liquids 1,4-dichlorobutane and 1-bromo-4-chlorobutane as a function of temperature and pressure through calorimetric measurements against pressure. The isobaric thermal expansivity of 1-bromo-4-chlorobutane was determined over the temperature range from 273.15 to 423.15 K at pressures up to 200 MPa. Experimental results were used to model a general density scaling-based equation of state and to analyze the pressure–temperature behavior of the thermal expansion coefficient. It was confirmed that the investigated liquids exhibit a characteristic pressure range in which (∂αP/∂T)P = 0. [1]

Figure1:  transient optical absorption spectrum of 1-Bromo-4-chlorobutane

Figure 1 displays the transient optical absorption spectrum recorded during pulse radiolysis of an O₂‑saturated aqueous solution containing 1-bromo-4-chlorobutane (8.7 × 10⁻³ mol dm⁻³, [HClO₄] = 7.8 mol dm⁻³) at 3.5 μs after the pulse. The spectrum shows an absorption band with λmax = 380 nm. This band decays by first‑order kinetics with t₁/₂ = 9.3 μs. At low solute concentrations [(4–8) × 10⁻³ mol dm⁻³], the intensity of the band remained nearly constant. When the concentration of 1‑bromo‑4‑chlorobutane was increased, the absorbance in the 400–500 nm region rose, although no distinct peak could be resolved. [2]

Synthesis

Figure2: Synthesis of 1-Bromo-4-chlorobutane

A stirred and cooled (0 °C) mixture containing the previously mentioned alcohol (4.0 g, 0.036 mol) along with pyridine (1.0 mL) was treated with PBn₃ (1.5 mL) via injection. The resulting mixture was kept under stirring at 0 °C for 1 hour, followed by continued stirring at room temperature for an additional 3 hours. Upon completion of the reaction, the mixture was diluted with ice‑cold water and then extracted with diethyl ether (3 × 30 mL). The combined organic layer was sequentially washed with water, aqueous dilute HCl (2 N), water again, and finally brine. After drying over a suitable desiccant and removing the solvents under reduced pressure, the crude residue was subjected to distillation, affording 1-bromo-4-chlorobutane. 1-bromo-4-chlorobutane was subsequently subjected to four consecutive rounds of distillation to achieve further purification. [2]

Thermal expansion coefficient

The transitiometric measurements and equation-of-state modeling of the thermal expansion coefficient for liquid 1,4-dichlorobutane and 1-bromo-4-chlorobutane, conducted over the temperature range from 273.15 to 423.15 K and pressures up to 200 MPa, yield the following conclusions. The isotherms of thermal expansivity for 1,4-dichlorobutane and 1-bromo-4-chlorobutane intersect within characteristic pressure ranges of 38.5–73.9 MPa and 31.4–100.9 MPa, respectively. Below these respective pressure ranges, thermal expansion increases with temperature, (∂αp/∂T)p > 0, whereas at higher pressures αp decreases with temperature. Within the characteristic pressure range, 1-bromo-4-chlorobutane exhibits a temperature-independent behavior where (∂αp/∂T)p = 0. [1]

Nucleophilic substitution reaction

Add phenol derivative (10.0 mmol, 1.0 eq.), 1-bromo-4-chlorobutane (12.0 mmol, 1.2 eq.), K2CO3 (12.0 mmol. 1.2 eq.) and DMF (20 mL) to a 50 mL screw capped vial equipped with a magnetic stirring bar. Place the reaction mixture in a pre-heated oil bath at 60°C and stir vigorously for 6 hours. Cool the mixture to ambient temperature.Dilute the reaction mixture with deionized water (100 mL). Extract the mixture with ethyl acetate (EA) (10 mLx3). Dry the organic layer over anhydrous Na2SO4. Concentrate the organic layer under reduced pressure. Purify the residue by flash chromatography (PE/EA = 80/1) to obtain 4-(4-chlorobutoxy)benzonitrile. [3]

Reference

[1] Chora?z?ewski M, Grzybowski A, Paluch M. Isobaric thermal expansion of compressed 1, 4-dichlorobutane and 1-bromo-4-chlorobutane: transitiometric results and a novel application of the general density scaling-based equation of state[J]. Industrial & Engineering Chemistry Research, 2015, 54: 6400-6407.

[2] Maity D K, Mohan H, Chattopadhyay S, et al. Formation, Stability, and Reactivity of Radical Cations of 1-Bromo-n-chloroalkanes in Aqueous Solution: A Pulse Radiolysis Study[J]. The Journal of Physical Chemistry, 1995, 99: 12195-12203.

[3] Chen, Youwen; et al, Fe/Mn-Synergistic Promoted C(sp3)-Bi Cross-Coupling of Alkyl Chlorides with Chlorobismuthanes to Access Air-Stable Alkylbismuthanes, Organic Letters 2025, 27, 3578-3583.

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