Convenient Synthesis of More Complex 2-Substituted 4(3H)-Quinazolinones via Lithiation of 2-Alkyl-4(3H)-quinazolinones

1999 ◽  
Vol 64 (3) ◽  
pp. 515-526 ◽  
Author(s):  
Keith Smith ◽  
Gamal A. El-Hiti ◽  
Mohamed F. Abdel-Megeed ◽  
Mohamed A. Abdo
Keyword(s):  
Addition Product ◽  
Phenyl Isocyanate ◽  
Lithium Diisopropylamide ◽  
Methyl Group ◽  
Convenient Synthesis

2-Methylquinazolin-4(3H)-one has been doubly lithiated, at nitrogen and in the 2-methyl group, with n-butylithium. The lithium reagent thus obtained reacts with a variety of electrophiles (iodomethane, D2O, phenyl isocyanate, benzaldehyde, benzophenone, cyclopentanone, 2-butanone, carvone) to give the corresponding 2-substituted derivatives in very good yields. Reaction of the dilithio reagent with acetonitrile gives an α,β-unsaturated imine by tautomerization of the initial addition product. Double lithiation of 2-ethyl- and 2-propyl-4(3H)-quinazolinones can be achieved using lithium diisopropylamide and the lithiated reagents thus obtained react with similar electrophiles to give the corresponding products in very good yields. In the reaction of the dianion of the 2-ethyl-4(3H)-quinazolinone with iodine, an oxidatively dimerised product was obtained. Lithiation of 2-unsubstituted 4(3H)-quinazolinone does not take place on C-2 under similar conditions.

Pterins. VIII. The absolute configuration at C 6 of natural 2-Amino-6-[(1'R,2'S)- 1',2'-dihydroxypropyl]-5,6,7,8-tetrahydropteridin-4(3H)-one (L-erythro-5,6,7,8-tetrahydrobiopterin)

1982 ◽  
Vol 35 (4) ◽  
pp. 785 ◽  
Author(s):  
WLF Armarego ◽  
P Waring ◽  
B Paal
Keyword(s):  
Hydrochloric Acid ◽  
Absolute Configuration ◽  
Side Chain ◽  
Methyl Group ◽  
Convenient Synthesis ◽  
The Absolute

The conformation of the side chain of 5,6,7,8-tetrahydrobiopterint (6) in 0.5 M DCl/D2O is predominantly quasi-equatorial (deduced from 3J (13C4a, 1H6) 1.1 HZ), and is the same as that of the methyl group in 2-methyl-1,2,3,4-tetrahydroquinoxaline and in 2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one in the same solvent. Because (-)-(2S)-2-methyl-1,2,3,4-tetrahydroquinoxaline(4) and (-)-(6S)-2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one (5) have the same conformation and negative c.d. spectra (O 248 nm and 263 nm respectively) as does the natural 5,6,7,8, tetrahydrobiopterin (O minimum at 265 nm) in 0.1 M hydrochloric acid, then the absolute conformations of the tetrahydropyrazine rings and the absolute configurations at the chiral centres C2, C6, and C6 of compounds (4), (5) and (6) respectively are the same. Hence the absolute configuration at C6 in natural 5,6,7,8 tetrahydrobiopterin is R.� A convenient synthesis of biopterin on a gram scale is described.

Direct Introduction of a Methyl Group at the C5‐Position of 1,2,4‐Triazines: Convenient Synthesis of 6‐Functionalized 5‐Aryl‐2,2′‐bipyridines

2020 ◽  
Vol 5 (9) ◽  
pp. 2753-2755 ◽  
Author(s):  
Alexey P. Krinochkin ◽  
Dmitry S. Kopchuk ◽  
Igor S. Kovalev ◽  
Sougata Santra ◽  
Grigory V. Zyryanov ◽  
...  
Keyword(s):  
Direct Introduction ◽  
Methyl Group ◽  
Convenient Synthesis

Chiral Induction in the Methylation of N-Ethoxycarbonylmethyl Sulfoximines

1986 ◽  
Vol 39 (11) ◽  
pp. 1833 ◽  
Author(s):  
TW Hambley ◽  
TW Hambley ◽  
B Raguse ◽  
B Raguse ◽  
DD Ridley ◽  
...  
Keyword(s):  
Carbon Atom ◽  
Absolute Configuration ◽  
Sulfur Atom ◽  
Optically Active ◽  
Complex Mixtures ◽  
Lithium Diisopropylamide ◽  
Aryl Group ◽  
Methyl Group ◽  
X Ray ◽  
Chiral Induction

Chiral inductions in the C- methylations of four optically active N-ethoxycarbonylmethyl-S-p-tolylsulfoximines were explored by using the reagents lithium diisopropylamide (in tetrahydrofuran at -78°) then methyl iodide. When the fourth substituent at sulfur was a methyl group, complex mixtures of products were formed. However, when the fourth substituent was an aryl group, moderate yields of methylated compounds were formed and the ratio of diastereomers produced were 50 : 50 ( Ar = phenyl), 76 : 24 ( Ar = o- methoxyphenyl ) and 100 : 0 [ Ar = o-(2-methoxyethoxy)phenyl]. The diastereoselectivities are accounted for by intramolecular chelation of the aryl-oxygen substituents with the intermediate lithiated carbanion. The structure and absolute configuration where Ar = o-(2-methoxyethoxy )phenyl were confirmed by X-ray crystallographic methods. Space group P 212121, orthorhombic, a 10.2500(7), b 13.281(2), c 16.526(2) Ǻ; final R 0.064 (on 924F). The configuration at the sulfur atom is (S) and that induced at the carbon atom is (R).

Use of [13C-methyl]Tropinone to follow the fate of the methyl group during calystegine formation in root cultures of Solanum dulcamara (Solanaceae)

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
TA Bartholomeusz ◽  
R Molinié ◽  
A Roscher ◽  
AC Freydank ◽  
B Dräger ◽  
...  
Keyword(s):  
Root Cultures ◽  
Solanum Dulcamara ◽  
Methyl Group

STEROIDSTRUKTUR UND LEBERTOXIZITÄT

1967 ◽  
Vol 54 (1) ◽  
pp. 73-84 ◽  
Author(s):  
H. L. Krüskemper ◽  
G. Noell
Keyword(s):  
Alkaline Phosphatase ◽  
Liver Function ◽  
Blood Coagulation ◽  
Electrophoretic Pattern ◽  
Coagulation Factors ◽  
Blood Coagulation Factors ◽  
Methyl Group ◽  
Liver Functions ◽  
Male Subjects ◽  
Androstane Derivatives

ABSTRACT In male subjects investigations have been carried out regarding the effect of C1- and C17-methylated androstane derivatives (20 mg per day, orally, two weeks) on liver functions (parameters: activities of GPT, GOT, alkaline phosphatase and cholinesterase in serum; electrophoretic pattern; blood coagulation factors V, VII, X and prothrombin; BSP-retention). In addition to the well known hepatotropic action of 17α-alkylated C-19-steroids a quasi-axial 1α-methyl configuration (in 1α-methylandrost-2-en-17β-ol) definitely increased BSP-retention and several coagulation factors. These steroid effects decreased gradually when a methyl group was introduced in C1 equatorially (1-methylandrost-1-en-17β-ol-3-one) or quasi-equatorially (1β-methylandrost-2-en-17β-ol), the latter compound completely lacking from any influence on parameters of liver function under investigation.

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