Org. Synth. 1949, 29, 31
DOI: 10.15227/orgsyn.029.0031
[Thiophene, 2-chloromethyl-]
Submitted by K. B. Wiberg and H. F. McShane.
Checked by Cliff S. Hamilton and J. L. Pauley.
1. Procedure
Caution! Suitable precautions should be observed in the preparation, purification, and storage of 2-chloromethylthiophene. The product is lachrymatory, and the procedure should be carried out in an efficient hood. The distillation and storage of the material are described in (Note 6) and (Note 7).
In a 2-l. beaker surrounded by an ice-salt bath (Note 1), and fitted with a mechanical stirrer and a thermometer, are placed 420 g. (392 ml., 5 moles) of thiophene (Note 2) and 200 ml. of concentrated hydrochloric acid. A rapid stream of hydrogen chloride (Note 3) is passed continuously into the mixture with vigorous stirring. When the temperature reaches 0°, 500 ml. of 37% formaldehyde solution (Note 4) is added at a rate that will permit the temperature to remain below 5°. The addition requires about 4 hours. When all the formaldehyde solution has been added, the mixture is extracted with three 500-ml. portions of ether. The ether extracts are combined, washed successively with water and saturated sodium bicarbonate solution, and then dried over anhydrous calcium chloride. The solvent is removed by distillation, and the product is distilled under reduced pressure through a 50-cm. fractionating column (Note 5). The product boiling at 73–75°/17 mm. is collected. The yield is 257–267 g. (40–41%) of a colorless oily liquid (Note 6) and (Note 7).
2. Notes
1. The checkers preferred to use a Dry Ice bath or to add Dry Ice to the reaction mixture as needed.
2. The thiophene used by the submitters was that supplied by the Socony-Vacuum Oil Company. It was used without any additional purification.
3. A satisfactory hydrogen chloride generator has been described earlier.1
4. The apparatus should be set up in a hood, for, although nearly all the hydrogen chloride is absorbed, a small amount does escape. The rate of addition of hydrogen chloride should be such that nearly complete absorption is maintained at all times.
According to the submitters, paraformaldehyde (165 g., 5.5 moles) may be substituted for the formaldehyde solution. This modification affords an easier control of the temperature. However, paraformaldehyde does not react to any appreciable extent below 0°, and so the temperature should be kept between 0° and 5°. The reaction time is 6–8 hours, and the yield is unchanged.
5. A Vigreux column was used by both the submitters and checkers.
6. Some bis-(2-thienyl) methane may be obtained from the residue at 125–126°/9 mm. When recrystallized from methanol it melts at 46–47°.
7. It is advisable not to store chloromethylthiophene for any length of time or in sealed containers, since it has a tendency to decompose, often with explosive violence, even when kept cold and in the dark. If the product is to be used for the preparation of 2-thiophenaldehyde it is convenient to convert it to the more stable hexamethylenetetrammonium salt, for storage.
Instances of explosion of the product on storage have been reported; these are apparently due to generation of hydrogen chloride within a closed container. The following procedure for distillation and storage is recomended (F. C. Myer, private communication). The crude product is stabilized by the addition of 2% by weight of dicyclohexylamine and purified by rapid distillation under reduced pressure. The pot temperature should not rise above 100° during the main part of the distillation, or above 125° at the end of the distillation. The distillate is stabilized immediately with 1–2% by weight of dicyclohexylamine and stored in a glass bottle plugged loosely with a stopper wrapped with glass wool. The bottle is placed in a large beaker and stored in a refrigerator. A small amount of gelatinous salt separates on standing; this has no deleterious effect.
When stabilized properly and stored in the cold, decomposition is slow. The material should be inspected regularly to observe excessive darkening and liberation of hydrogen chloride. Restabilization and distillation may permit recovery of pure material if the decomposition is not too far advanced. Complete decomposition results in frothing, resinification, and liberation of hydrogen chloride.
3. Discussion
2-Chloromethylthiophene has been prepared by the action of hydrogen chloride on 2-thienylcarbinol2 and by the action of hydrogen chloride and formaldehyde on thiophene.3 The above procedure is essentially that of Blicke and Burckhalter.3
This preparation is referenced from:

References and Notes
  1. Org. Syntheses Coll. Vol. 1, 534 (1941).
  2. Biedermann, Ber., 19, 636 (1886).
  3. Blicke and Burckhalter, J. Am. Chem. Soc., 64, 477 (1942).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

calcium chloride (10043-52-4)

hydrogen chloride,
hydrochloric acid (7647-01-0)

methanol (67-56-1)

ether (60-29-7)

formaldehyde (50-00-0)

sodium bicarbonate (144-55-8)

Thiophene (110-02-1)

Thiophene, 2-chloromethyl-,
chloromethylthiophene (765-50-4)


dicyclohexylamine (101-83-7)

2-thienylcarbinol (636-72-6)

bis-(2-thienyl) methane (4341-34-8)

paraformaldehyde (30525-89-4)