Org. Synth. 1953, 33, 93
DOI: 10.15227/orgsyn.033.0093
Submitted by E. Campaigne, R. C. Bourgeois, and W. C. McCarthy1.
Checked by Charles C. Price and E. A. Dudley.
1. Procedure
Hexamethylenetetramine (77 g., 0.55 mole) is dissolved in 200 ml. of chloroform, and 88 g. (0.5 mole) of 3-thenyl bromide (p.921) is added as rapidly as possible with shaking (Note 1). A reflux condenser is attached, and the mixture is refluxed over a steam bath for 30 minutes. After being cooled, the mixture of chloroform and crystalline product (Note 2) is poured into 250 ml. of water and stirred until all the salt dissolves. The chloroform layer is separated and washed twice with 125-ml. portions of water, and the combined water extracts are steam-distilled. When the distillate comes over clear (about 1 l. of distillate is usually collected), it is acidified with a little hydrochloric acid (Note 3) and extracted with three 100-ml. portions of ether. After drying over Drierite, the ether is evaporated, and the residue is distilled. 3-Thenaldehyde is collected at 72–78°/12 mm. or 195–199°/744 mm., nD20 = 1.5860 (Note 4). The yield is 30–40 g. (54–72%).
2. Notes
1. The reaction mixture refluxes spontaneously, and it is necessary to be cautious in adding the reagents to prevent the chloroform from boiling over.
2. The crystalline hexamine salt may be isolated and recrystallized at this step. It softens at 120° and melts with decomposition at 150°.
3. The Sommelet procedure2 yields a mixture of aldehyde and amines. Acidification removes the amines from the ether extract.
4. The checkers obtained the product, b.p. 80–81°/14 mm.
3. Discussion
3-Thenaldehyde has previously been prepared by Steinkopf and Schmitt3 from 3-thienylmagnesium iodide and ethyl orthoformate in low yield. The first application of the method described here was reported by Campaigne and LeSuer.4 3-Thenaldehyde also has been obtained from 3-thenoic acid by the Sonn-Müller procedure5 and from 3-bromothiophene by treatment with butyllithium and dimethylformamide.6
This preparation is referenced from:

References and Notes
  1. Indiana University, Bloomington, Indiana.
  2. Sommelet, Compt. rend., 157, 852 (1913).
  3. Steinkopf and Schmitt, Ann., 533, 264 (1938).
  4. Campaigne and LeSuer, J. Am. Chem. Soc., 70, 1555 (1948).
  5. Nishimura, Motoyama, and Imoto, Bull. Univ. Osaka Prefect., Ser. A, 6, 127 (1958) [C. A., 53, 4248 (1959)].
  6. Gronowitz, Arkiv Kemi, 8, 441 (1955).

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


hydrochloric acid (7647-01-0)

ether (60-29-7)

chloroform (67-66-3)

Ethyl orthoformate

hexamethylenetetramine (100-97-0)

butyllithium (109-72-8)

dimethylformamide (68-12-2)


3-Thiophenecarboxaldehyde (498-62-4)

3-Thenyl bromide

3-thienylmagnesium iodide

3-Thenoic acid

3-Bromothiophene (872-31-1)