Methadone is an analgesic drug with a similar activity to morphine and is used in treating heroin ad — Physical Chemistry — Thermodynamics Chemistry Question
The synthesis of methadone
Methadone is an analgesic drug with a similar activity to morphine and is used in treating heroin addicts. It may be prepared as its hydrochloride salt by the following multi-stage synthesis:
[VISUAL]
Intermediate C is a chloride salt and may be prepared by treating two isomeric compounds with SOCl2 and then heating up the reaction mixture:
[VISUAL]
Deduce the structures for the compounds V, W and X.
Model Answer
V: 2-bromo-2-phenylacetonitrile (PhCH(Br)CN)
W: 2,2-diphenylacetonitrile (Ph2CHCN)
X: sodium 1-cyano-1,1-diphenylmethanide (sodium salt of 2,2-diphenylacetonitrile, Ph2C(Na)CN)
Deduce the structures for the compounds A, B and hence for the intermediate C.
Model Answer
A: 1-(dimethylamino)propan-2-ol
B: 2-(dimethylamino)propan-1-ol
C: 2-chloro-N,N-dimethylpropan-1-amine hydrochloride (equilibrium mixture with its isomer 1-chloro-N,N-dimethylpropan-2-amine hydrochloride formed via a cyclic aziridinium ion intermediate)
Deduce the structures for the compounds Y, Z and methadone hydrochloride.
Model Answer
Y: 4-(dimethylamino-2,2-diphenylpentanenitrile
Z: 6-(dimethylamino-4,4-diphenylheptan-3-imine magnesium bromide derivative
Methadone hydrochloride: 6-(dimethylamino-4,4-diphenylheptan-3-one hydrochloride
Assign, as fully as possible, the 1H NMR spectrum of methadone. 1H NMR δ 7.40–7.30 (10H, m), 2.78 (1H, dqd, 10.6 Hz, 6.2 Hz, 2.3 Hz), 2.49 (2H, q, 6.8 Hz), 2.26 (6H, s), 2.22 (1H, dd, 11.5 Hz, 10.6 Hz), 2.00 (1H, dd, 11.5 Hz, 2.3 Hz), 1.10 (3H, d, 6.2 Hz), 1.05 (3H, t, 6.8 Hz).
Model Answer
The 1H NMR spectral assignments for methadone are as follows:
- δ 7.40–7.30 (10H, m): Aromatic protons of the two phenyl groups
- δ 2.78 (1H, dqd, J = 10.6, 6.2, 2.3 Hz): CH proton adjacent to nitrogen (C6-H)
- δ 2.49 (2H, q, J = 6.8 Hz): CH2 protons of the ethyl group (C2-H2)
- δ 2.26 (6H, s): Methyl protons on the dimethylamino group (-N(CH3)2)
- δ 2.22 (1H, dd, J = 11.5, 10.6 Hz): One of the diastereotopic CH2 protons in the main chain (C5-H)
- δ 2.00 (1H, dd, J = 11.5, 2.3 Hz): The other diastereotopic CH2 proton in the main chain (C5-H)
- δ 1.10 (3H, d, J = 6.2 Hz): Methyl protons adjacent to nitrogen (C7-H3)
- δ 1.05 (3H, t, J = 6.8 Hz): Methyl protons of the ethyl group (C1-H3)
Draw the structure of the biologically active enantiomer of methadone.
Model Answer
The biologically active enantiomer of methadone is (R)-methadone. Its structure features the chiral center at C6 in the (R)-configuration.