1,2-Azoles and 1,3-Azoles 121Diazoalkanes will also add to alkynes.
Synthesis of isothiazoles from -amino,-unsaturated carbonyl
compounds(1,2-bond made)
Because unsubstituted thiohydroxylamine is not available, ring-closing N-S bond formation is the most common
method of synthesis of isothiazoles. The ring closure of -amino,-unsaturated thioketones (usually generated
in situ by reaction with P 4 S 10 ) or -amino,-unsaturated thioamides, in the presence of an oxidising agent (iodine
in the example shown below), leads to isothiazoles.
Exercises
- What are the structures of the halogen-containing compounds formed in the following ways:
(i) imidazole reacted with NaOCl → C 3 H 2 Cl 2 N 2 ;
(ii) 1-methylimidazole reacted with excess Br 2 in AcOH → C 4 H 3 Br 3 N 2 then this reacted with EtMgBr fol-
lowed by water → C 4 H 4 Br 2 N 2 and this in turn with n-BuLi then (MeO) 2 CO giving C 6 H 7 BrN 2 O 2. - What are the structures for the isomeric products C 9 H 7 N 3 O 2 , formed when 1-phenylpyrazole is reacted
with:
(i) c. H 2 SO 4 –c. HNO 3 or
(ii) Ac 2 O–HNO 3. Explain the formation of different products under the two sets of conditions. - When the methyl ester of histidine is reacted with carbonyl diimidazole, a product C 8 H 9 N 3 O 3 is formed – what
is its structure? Reaction of this substance with iodomethane takes place easily producing a salt C 9 H 12 N 3 O 3 I,
which on simple treatment with methanol leads to C 10 H 15 N 3 O 4 – what is the structure of this product? - What are the structures of the intermediates and fi nal products that are formed when:
(i) 4-phenyloxazole is heated with but-3-yn-2-one → C 6 H 6 O 2 ; and
(ii) 5-ethoxyoxazole is heated with dimethyl acetylenedicarboxylate → C 10 H 12 O 6. - Draw all the important resonance contributors to the münchnone, 3-methyl-2,4-diphenyl-1,3-oxazolium-
5-olate. Predict the structure of the product of its reaction with methyl propiolate (HCKCCO 2 Me). - Deduce structures for the products obtained by treating 5-methylisoxazole with SO 2 Cl 2 → C 4 H 4 ClNO, and
this with aqueous sodium hydroxide → C 4 H 4 ClNO (which contains no rings). - Deduce structures for each of the products formed in the following sequence: 1-methylimidazole/
n-BuLi at –30 °C then TMSCl (Me 3 SiCl) → C 7 H 14 N 2 Si then this with n-BuLi at –30 °C then TMSCl →
C 10 H 22 N 2 Si 2 , then this with MeOH–rt → C 7 H 14 N 2 Si, which is different to the fi rst product. - What are the structures of the 1,3-azoles that are produced from the following reactant combinations:
(i) 1-chlorobutan-2-one and thiourea;
(ii) thiobenzamide and chloroacetaldehyde;
(iii) thioformamide and ethyl bromoacetate; and
(iv) 2-amino-1,2-diphenylethanone and cyanamide (H 2 NCKN). - Draw the structures of the two products that are formed when hydroxylamine reacts with PhCOCH 2 CH=O.
Suggest an unambiguous route for the preparation of 5-phenylisoxazole. - Devise a mechanism to explain the generation of a nitrile oxide (RCKN-O) ready for 1,3-dipolar cycload-
ditions, by treatment of a nitroalkane (RCH 2 NO 2 ) with phenyl isocyanate (PhN=C=O).