SECTION V.

ORGANIC CHEMISTRY
Problem1
Organic compounds with NN bond occur sparsely in Nature. In 1966 bioactive achiral
compound W (C12H12N2) was isolated from the roots of Withania somnifera (ashwagandha,
Indian giseng); the important component in Ayurvedic medicine. This compound received
name withasomnine. In 1994 from Newbouldia laevis a dihydro derivative of withasomnine
was isolated. This compound N (C12H14N2), which is referred to as newbouldine, exists in
Nature as (S,S)-isomer. Methods for the syntheses of compounds W and ()-N are given in
the Scheme below. The key steps of syntheses are dipolar [3+2]-cycloadditions.
O
Si B PhI
O
NaNO2 (CF3CO)2O O Bu4NF PdCl2(PPh3)4
N A B C D W
H OH HCl/H2O CF3COOH 180C, -CO2 K3PO4 THF/H2O
C5H6N2O2
HO O N S DDQ Raney Ni
HN H
CHCl3
1) LiAlH4 N N hn C13H14N2S
E F G
2) H2O DIAD, PPh3 MeCN
Cl Cl C13H16N2S
THF C13H16N4S
HCl N H Cp2ZrHCl
DDQ = O O HN N
Cp = cyclopentadienyl H2O THF
-20C
NC CN DIAD = i-Pr-OOC COO-i-Pr O
is bicyclic mesoionic compound, i.e., heterocyclic compound with exocyclic atom(s)
wherein charges are delocalized and a completely uncharged structure cannot be written.
Both W and N have 10 signals in 13 NMR spectra; 1 NMR spectrum of W is given below.
7.82 1
NMR spectrum of withasomnine (CDCl3, 400 MHz)
A
10 4.18 2.67
7.34 3.10
G
C
B F 2.69
7.32 4.16 2.65
4.20 3.08
5 7.19 3.12

7.21
E
7.17 4.14 2.70
4.24 4.12 2.63
D 4.26 4.10 2.61

0
8 7 6 5 4 3 2 1 0
1. Decipher scheme. Write down structural formulae of compounds , N, W.
2. Assign signals in 1 spectrum of withasomnine (see answer sheets).
3. How many isomers of F can be formed in reaction of E with 5-( methylsulfanyl) tetrazole?

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Problem 2
Vinylcyclopropane-to-cyclopentene rearrangement (VCR) as well as the analogous
reactions of the corresponding heteroatom compounds are considered the important method
for the synthesis of five-membered carbo- and heterocycles. These rearrangements can be
performed under thermal, photochemical or catalytic activation. Thermal and photochemical
reactions proceed via formation of the most stable biradical.
R R 2 R 2
2
5 R 2
5
t 5 5
1 4
3 3
4 3
3 1 1 1
4 4
1. Write down structural formulae for products of two reactions given below accounting
for facts that: a) both reactions are examples of VCR; b) molecule of Y has symmetry axis
of the second order.
O

t t
X Y

VCR was the first step in the total synthesis of terpene hydrocarbon ()-zizaene (Z):
450oC KOH (CH2=CH)2CuLi 1) LiN(i-Pr)2, THF NaIO4
O A B C D
Me2S/Et2O 2) PhSSPh 120C
C10H14O C12H18O C18H22OS
E
1) B H C 12H 16O
2 6
Na/Hg t-BuOK mCPBA 2) H2O2, NaOH 1) PhSH
J I H G F
C14H22O2 Na2HPO4 C H O SHMPA 3) TsCl, Py 2) (CH2OH)2
NaH2PO4 20 26 4 C20H26O2S H+

OH
H2C2O4
mCPBA = O
H Cl
CH3I (2 eq.) CH3PPh3 I O
K L H
C2H5ONa BuLi O N
Z HMPA = P
N
N
2. Write down extent of unsaturation in zizaene (Z)?
3. How many isomers can exist for zizaene?
4. Decipher scheme of this synthesis: write down structural formulae of compounds A L.

Problem 3
High CH acidity of carbonyl compounds is widely using in organic synthesis for the
preparation of new, more complex compounds. For example:

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 1) NaH O 1) EtONa
A + D1 + D2 A + B + C
2) Cl 2) Cl

EtONa

B + C
Compounds D1 and D2 are the major products when two-fold excess of allyl chloride
is using. Ozonolysis of the product followed by treatment of ozonide with zinc and acetic
acid produces formaldehyde and compound E (C5H8O2), the similar treatment of affords
acetone and F (342). Compound is formed by dehydration of . 1 NMR spectra of
D2, E and F contains, respectively, 5, 4 and 2 signals with the relative intensity of
2 : 2 : 1 : 1 : 1, 3 : 2 : 2 : 1 and 3 : 1.
1. Write down structural formulae of , , , D1, D2, and F.
One of the best methods for the regioselective alkylation of ketones consists in an
activation of the required -carbon atom. For example:
O O Cl Cl 1) NaOH/H2O
NaH n-BuLi
G J K L D2
O C6H9O3Na C6H8O3NaLi 2) H3O+, -CO2

Cl

1) NaOH/H2O 1) NaH 1) NaOH/H2O

A +
H I D1
2) H3O , -CO2 2) Cl 2) H3O+, -CO2
2. Write down structural formulae of compounds G L.
Auxiliary functional groups can be used for the selective activation of one of the
alternative -carbon atoms:
1) LDA KNH2 Ph Cl Ph Cl KOH
O N P Q S T
2) HCOOEt C H O Li EtOH
8 11 2 KOH
O
1) EtONa EtOH
Ph Cl
2) CH3I KOH LDA = LiN(i-Pr)2
M O R
EtOH
3. Write down structural formulae of compounds T.
For the synthesis of cycloalkanones with geminal substitution, methods of blockage of
one of the -carbon methods is often used (W is microwave irradiation):
O
KOH
LDA 1) EtONa 1) EtONa EtONa t, mW
Y1 U M V W X Y2
2) Cl KOH 2) Cl H2 O
I I
4. Write down structural formulae of compounds U X, Y1 and Y2, if bicyclic
compounds Y1 and Y2 are isomers, Y2 having no carbonyl group.

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