AFM, SPM
D. A. Cheshkov
3. Advanced Methods of Organic Synthesis: Poster presentation P-28 AN EXPERIMENTAL AND THEORETICAL INVESTIGATION OF THE BASE-CATALYZED
REARRANGEMENT OF 4A-ACETYL-8A-
HYDROXYDECAHYDROQUINAZOLINE-2-THIONE Moscow State Academy of Fine Chemical Technology, Department of Organic Chemistry, Moscow, Russia
3. Advanced Methods of Organic Synthesis: Poster presentation P-29 ACYLATIVE KINETIC RESOLUTION OF 2-METHYL-
1,2,3,4-TETRAHYDROQUINOLINE USING 2-ARYLPROPIONYL CHLORIDES
Postovsky Institute of Organic Synthesis of RAS (Ural Division), Ekaterinburg, Russia
E.N. Chulakov G.L. Levit A.A. Tumashov D.N. Kozhevnikov
V.P. Krasnov chulakov@ios.uran.ru
Acylative kinetic resolution (KR) is widely used to obtain the optically pure amines, the use of chiral acylating agents being of particular interest. Earlier we showed that (2S)-2-(6- metoxynapht-2-yl)propionyl chloride is an effective agent for KR of 7,8-difluoro-2,3-dihydro-3- methyl-4H-[1,4]benzoxazine – a key intermediate in the synthesis of antibacterial agent levofloxacin.
In this work we present the results of KR of 2-methyl-1,2,3,4-tetrahydroquinoline (1) using 2-arylpropionyl chlorides 2a-c under various conditions. To determine the optimal conditions for KR we used the resolving agents in racemic form. In this case, the stereo selectivity factor is equal to the ratio of the diastereoisomeric amides formed.
NH Me
N Me
O Me Ar
N Me
O Me Ar
N Me
O Me Ar
N Me
O Me Ar Ar
Me
O
+ Cl + +
(RS)-1
(RS)-2a-c
2a: Ar = 6-MeO-Napht-2-yl 2b: Ar = 4-iBu-C6H4 2c: Ar = Ph
(S,S)-amide (R,R)-amide (R,S)-amide (S,R)-amide
major minor
solvent, T oC, 6 h +
0.5 equiv.
Table. Stereochemical results of acylation of amine 1 with acyl chlorides 2a-c dr = (S,S)/(R,S) or (R,R)/(S,R) Acylating agent Solvent
+20 °C –20 °C
PhMe 96.8/3.2 98.0/2.0
2a CH2Cl2 93.8/6.2 92.3/7.7
PhMe 97.0/3.0 98.1/1.9
2b CH2Cl2 91.8/8.2 93.8/6.2
PhMe 95.9/4.1 97.5/2.5
2с CH2Cl2 88.8/11.2 89.5/10.5
It was found that acylation of amine 1 with acyl chlorides 2a-c results in predominant formation of (S,S)[(R,R)]-amides. In all cases the most selective acylation of 1 was observed in toluene at –20 °C. Acylation in dichloromethane was less selective (see Table). Ibuprofen chloride (2b) was found to be more selective resolving agent in comparison with naproxen chloride (2a) and 2-phenylpropionyl chloride (2c). Thus, in the case of acylation of amine 1 in toluene at +20 °C with acyl chloride 2b the diastereoisomeric ratio (dr) of the amides formed was 97.0/3.0. The decrease in the reaction temperature from +20 to –20 °C provided an improvement in stereoselectivity (dr 98.1/1.9).
The reaction of amine 1 with 2c was calculated (DFT-D/B3LYP/TZVP) in dichlorometane (COSMO solvation model) at 293 K. Difference in the computed free energy of activation for (S,S)[(R,R)]- and (S,R)[(R,S)]-diastereomers (12.2 and 15.2 kcal/mol, respectively) agrees with the measured diastereoisomeric ratio. Weak ππ-interactions stabilizes the (S,S)[(R,R)] transition state due to the parallel position of aromatic rings of the reagents.
The work was financially supported by RFBR (grant 10-03-00084), the State Program for Supporting of Leading Scientific Schools of the RF (grant NSh 65261.2010.3), the State Contract 02.522.12.2011 and by the Ural Division of RAS (grants 09-P-3-2001, 09-I-3-2004, 10-3-NP-322).
3. Advanced Methods of Organic Synthesis: Poster presentation P-30 SYNTHESIS OF ORTHO-(DIMETHYLAMINO)ARYL
KETONES AND ACRIDONES BY THE REACTION OF 1,1-DIALKYLHYDRAZONES WITH ARYNES Iowa State University, Department of Chemistry, Ames, IA, USA A.V. Dubrovskiy
R.C. Larock anton@iastate.edu
A novel, efficient, and expedient route to biologically and pharmaceutically important o-(dimethylamino)aryl ketones and acridones has been developed starting from readily available aldehydes, 1,1-dimethyl hydrazine, and commercially available o- (trimethylsilyl)aryl triflates. The reaction proceeds under mild conditions, tolerates a wide range of functional groups, and provides final products in good to excellent yields.
TMS R H TfO
N NMe2
+ R
NH NMe2 CsF
R
O NMe2
MeCN
R = aryl, heteroaryl, alkenyl
N O
Me 1) HCl
2) MeONa
R =o-haloaryl HCl
3. Advanced Methods of Organic Synthesis: Poster presentation P-31 N-ACYLBENZOTRIAZOLE MEDIATED MICROWAVE ASSISTED SYNTHESIS OF PROTECTED AND NOVEL UNPROTECTED FERROCENOYLAMIDOAMINO ACIDS 1 - Anadolu University, Department of Chemistry, Eskisehir, Turkey
2 - Eskisehir Osmangazi University, Department of Chemistry, Eskisehir, Turkey
S.F. Ekti Dal1 D. Hur1 G.A. Varol2
E. Hur2 sfekti@anadolu.edu.tr
Ferrocene chemistry has aroused interest of many researcher as a result of its ability synthesizing a large number of derivatives and to be applicated in many field. It has been used in electron transfer process of amino acids and peptides because of its very favorable electrochemical properties. Its redox potential makes ferrocene important biomarker redox device by conjugation with biomolecules such as aminoacids, peptides, nucleic acids [1] and carbohydrates [2].
Ferrocene amino acids [3] and peptides [4], which are the important ferrocene derivatives, have found a great number of uses in many application such as binding or caging structures for metal ions [5].
In present work crystalline and chirally stable carboxyl-protected and novel unprotected N-ferrocenoyl amino acid derivatives of Ser, Cys, Ala, Phe, Trp, Asp and Asn have been prepared. These amino acids undergo substitution reaction with 1- (ferrocenylcarbonyl)-1H-benzotriazole in partially aqueous media under microwave irradiation.
Fe
1 O N N N
H2N CH2R
O OCH3 (L)
Fe
2a-d O HN
CH2R OCH3 O
H2N CH2R
O OCH3 (D,L)
Fe O HN
CH2R OCH3 O
2a-d +
(L)
(D) 3a-d H2N
CH2R O
OH (L) Fe
4a-g O HN
CH2R OH O (L)
Fe O HN
CH2R OH O 4f-g +
(D) 5a-b
H2N CH2R
O OH (D,L)
References:
[1] H.-B. Kraatz, Journal of Inorganic and Organometallic Polymers and Materials 15, 1 (2005) 83–106.
[2] M. Chahma, J. S. Lee, H.B. Kraatz, J. Organomet. Chem., 648 (2002) 81-86.
[3] J. Tauchman, P.Stepnicka, Inorg. Chem. Commun., 13 (2010) 149-152.
[4] C. C. G. Scully, P. J. Rutledge, Tetrahedron, 66 (2010) 5653–5659.
[5] F. E. Appoh, T. C. Sutherland, H.-B. Kraatz, J. Organomet. Chem. 690 (2005) 1209–1217.
3. Advanced Methods of Organic Synthesis: Poster presentation P-32 PHOSPHORYLATED
THIAZOLO[3,2-b][1,2,4]TRIAZOL-7-YLIUM CHLORIDES
Saint-Petersburg State Institute of Technology (Technical University), Department of Organic Chemistry, Saint-Petersburg, Russia
E.B. Erkhitueva A.V. Dogadina A.V. Khramchikhin
B.I. Ionin erhitouevae@yandex.ru
A number of condensed heterocyclic compounds containing triazole ring are known to possess diverse pharmacological properties, including painkilling, anti-inflammatory, anticancer, antibacterial and radioprotecting [1]. To date, the phosphorus-containing compounds of such structure are unknown, although they are promising ones as they combine condensed heterocycles and phosphonate groups in one molecule that may lead to even greater variety of valuable biological properties. In [2] was shown that reactions of 4-amino-3-mercapto-5-phenyl-1,2,4- triazoles with 1-bromo-2-acylacetilenes proceed as a condensation involving amino- and mercapto groups resulting in respective condensed heterocycles:
R
O
Br
HS
Ph H2N
N N
N
R
O
NH N S
N N
Ph Br
H
We found that the reaction of dimethyl chloroactylenephosphonate with 4-amino-3- mercapto-5-alkyl(aryl)-1,2,4-triazoles proceeds readily in acetonitrile medium at room temperature at the mixing equivalent amounts of the starting reagents, to form condensed heterocyclic compounds of unusual structures, namely 3-amino-6-(dimethoxyphosphoryl)-2-alkyl(aryl)-3H- thiazolo[3,2-b][1,2,4]triazol-7-ylium chlorides I–V:
HS H2N
R
N N
N Cl
O O
O P
I-V R=H(I),Me(II),Et(III),Pr(IV),Ph(V)
O P O
O S
N N
N R
NH2 Cl
Ia-Va HO P
OH
O S
N N
N R
NH2 Cl
+
δP –8.6 ppm δP ≈ 2.6 ppm δP ≈ –6.5 ppm
Similar compound is formed in the reaction of 4-methyl-3-mercapto-1,2,4-triazole with chloroacetylenephosphonate. The compounds I–V are crystalline substances, poorly soluble in organic solvents, well soluble in water. When heated in concentrated hydrochloric acid, they are transformed into the corresponding phosphonic acids Ia–Va. The structure of the compounds I–V, Ia–Va was proved using 1H, 13C, and 31P NMR spectroscopy. For example, in the 1H NMR spectrum of compound II there is a doublet signal of the methoxy groups at the phosphorus, δ 3.94, JHP 11.6 Hz, the methyl group in 2 position induces a singlet δ 2.72. Olefinic proton resonates in a weak field, δ 8.53, JHP 4.4 Hz. The 13C NMR spectrum of the compound contains the following signals (ppm): δC 10.12 (CH3), δC 55.66 (OCH3), δC 119.62, JCP 195.7 Hz (CH=), δC 132.28, JCP17.3 Hz (=CNH), δC 154.92 (=CCH 3), δC 161.39 (SC=N). Formation of the compounds I-V with aromatic structure is proved unambiguously by the data of X-ray diffraction and mass-spectrometry.
References:
[1] M. M. Ghorab and A. Y. Hassan, Phosphorus, Sulfur, and Silicon, 1998, 141, 251-260.
[2] T.E. Glotova, A. Nakhmanovich, and M.V. Sigalov, – Russian Journal of Organic Chemistry, vol. 24, 10, (1988), p. 1941-1945.
3. Advanced Methods of Organic Synthesis: Poster presentation P-33 THE FIRST EXAMPLES OF LIPOPHILIC AROMATIC
DIAZONIUM SALTS: PREPARATION AND PROPERTIES
National Research Tomsk Polytechnic University, Department of Biotechnology and Organic Chemistry, Tomsk, Russia
V.D. Filimonov M.E. Trusova P.S. Postnikov
K.V. Kutonova filimonov@tpu.ru
Arendiazonium dodecylbenzenesulfonates (ArN2+ p-C12H25C6H5SO3-) (ADBS) as the first example of aromatic diazonium salts with strongly pronounced lipophilic nature were obtained by diazotization of aromatic amines in the presence of p-dodecylbenzene sulfonic acid. The diazotization was carried out at room temperature in the presence of the polymer- supported nitrite in acetic acid or tert-butyl nitrite in ether, providing almost quantitative yields of ADBS. It was shown that ADBS are oily and relatively stable substances at room temperature, exothermic decomposed at 115-120 ° C with release of the energy about 200 J/g (DSC data) that is explosion safe substances.
ADBS are unlimited soluble in nonpolar organic solvents (benzene, hexane, CCl4, etc.), which sharply distinguishes them from known aromatic diazonium salts. It was shown that ADBS have typical diazonium nature, giving in high yields the products of azo- coupling, aryliodides by the reaction with KI, products of arylation with benzene and pyridine. At the same time they are also showing new and unprecedented properties for conventional diazonium salts. So ADBS form with quantitative yields arenes (hydro- dediazotization reaction) in hexane or chloroform, and arylchlorides at boiling in CCl4. In the presence of triethylamine ot pyridine.
These reactions have free-radical nature, as evidenced by the detection of hexachloroethane in the reaction mixture with CCl4 and CHCl3, and the benzyl radicals conversion products in the reaction with toluene.
Thus, lipophilic ADBS extend the known properties of aromatic diazonium salts, and open new possibilities for usage of diazonium compounds in organic synthesis.
3. Advanced Methods of Organic Synthesis: Poster presentation P-34 SYNTHESIS AND NITRATION OF
4-(2,2,2-TRINITROETHYLAMINO)-3-R-FUROXANS N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
A.O. Finogenov M.A. Epishina