Question

4. (16 pts) The drug Buspirone, marketed as Buspar Tabs "M, is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepine anti-anxiety agents, but it has an efficacy comparable to diazepam (Valium TM). It is used for the management of GAD, generalized anxiety disorders. [Ref: PubChem/DrugBank 13 15 12 11 16 N 18 10 28 24 20 27 21 Buspirone, Buspar Tabs 26 a. (2 pts) How many chiral stereocenters are present in this structure? b. (2 pts) Where would the C-O groups absorb in the IR? (Hint: the imide ring is a twist chair -how can this influence the structure and the frequencies?) 1740cm 1650 cm 1685 cm 1715 cm c. (2 pts) In the 'H-NMR spectrum, the range of the aromatic hydrogens is probably? d. (2 pts) In the 'H-NMR spectrum, where would you expect to find the hydrogens connected to C-10 and C-18? Use a range of 0.5 8 units. e. (3 pts) In the c-NMR spectrum, identify by number, which carbons will have absorbances at: 161 ppm 116ppmX 157ppm_ If more than one carbon will occur at the given frequency, please note this 172ppm f. (2 pts) How many unique "C signals will be seen in the spectrum? g (3 pts) The Mass spectrum of this compound will: Have an ever or odd parent ion mass? Would you expect a significant value for the M to M+2 ratio? -Show an M+ 1 intensity of approximately 20-25%, 25-30%, 30-35%?

Answer 1

a. The compound doesn't contain any chiral centre.

b. The carbonyl carbon would absorb near 1685 cm^-1, i.e. like an ordinary amide moiety. The twist chair conformation of the imide ring will force the imide carbonyl groups to stay on a plane, which makes both the carbonyl groups equivalent and the imide behaves as an amide.

c. The aromatic hydrogens will show their NMR peaks in the range 6.76-8.28, like the aromatic hydrogens of 2-pyrimidinamine.

d. The hydrogens attached to C-10 and C-18 resembles the aliphatic protons of 1-(2-Pyrimidinyl) piperazine and therefore expected to appear near 3.8 ppm in ¹HNMR.

e. The aromatic carbons of Buspirone resembles those of 1-(2-Pyrimidinyl) piperazine and therefore,-

C-15 will appear at 116 ppm

C-14, C-16 will appear at 157 ppm

C-12 will appear at 161 ppm

and the peak at 172 ppm is given by the imide carbonyl groups, i.e. C-2, C-20.

f. There will be 14 unique ¹³C peaks.

g. The mass spectrum is expected to have an odd parent mass.

Since there is no significant contribution from any isotopic mass, the M to M+2 ratio is expected to be very high.