REGIOMERS

http://www.google.com/patents/US7514563

FIG. 1 is a gHMBC spectrum of the borylation products of 4-chlorobenzonitrile. BELOW
 







FIG. 2 is a gHMBC spectrum of the borylation products of 4-bromobenzonitrile.
 






FIG. 3 is a gHMBC spectrum of the borylation product of 4-iodobenzonitrile.


 





FIG. 4 is a gHMBC spectrum of the borylation products of 4-methoxybenzonitrile.
FIG. 5 is a gHMBC spectrum of the borylation products of 4-thiomethylbenzonitrile.
FIG. 6 is a gHMBC spectrum of the borylation product of 4-dimethylaminobenzonitrile.
FIG. 7 is a gHMBC spectrum of the borylation product of methyl 4-cyanobenzoate.
FIG. 8 is a gHMBC spectrum of the borylation product of 4′-cyanoacetanilide.
FIG. 9 is a gHMBC spectrum of the borylation products of 1,5-dimethyl-2-pyrrolecarbonitrile.
FIG. 10 is a gHMBC spectrum of the borylation products of 5-methyl-2-furonitrile.



Regioisomer Assignment by NMR Spectroscopy:

From gHMBC NMR experiments, the two regioisomers for the borylation of 4-substituted benzonitriles can be distinguished unambiguously as in FIGS. 1 to 10. In isomer A, carbon atoms represented as C1 and C4 on the benzene ring, as well as C7 (nitrile carbon) are the three quaternary carbon atoms in the 100-170 ppm region (quaternary carbon C3 is typically not observed due to broadening from and coupling with boron). These three quaternary carbon atoms should show cross peaks due to long range H—C couplings (³J_C-H), which can be observed using gHMBC spectroscopy. In the gHMBC spectrum, carbon atoms C1 and C7 should show one cross peak each to proton H_c, whereas carbon atom C4 should show two cross peaks to protons H_a and H_b. Therefore the resulting number of cross peaks for C1, C4, and C7 should be 1, 2, and 1, respectively.
In Isomer B, carbon atoms represented as C1′, C4′, on the benzene ring, as well as C7′ (nitrile carbon) are the three quaternary carbon atoms in the 100-170 ppm region (quaternary carbon C2′ is typically not observed due to broadening from and coupling with boron). These three quaternary carbon atoms should show cross peaks due to long range H—C couplings (³J_C-H). In the gHMBC spectrum, carbon atoms C1′ and C7′ should show two cross peaks each, to protons H_d and H_e, whereas carbon atom C4′ should show only one cross peak to proton H_f. Therefore the resulting number of cross peaks for C1′, C4′, and C7′ should be 2, 1, and 2, respectively. Hence isomers A and B can be unambiguously assigned from gHMBC data.
For isomer A, with proton H_c unambiguously assigned by gHMBC, H_a and H_b can be assigned from their multiplicities. Proton H_a appears as a doublet, coupled to proton H_b with J≈2-3 Hz. Proton H_b appears as a doublet of doublets due to coupling to protons H_a and H_c. Carbon atoms C2, C6, and C5 were then assigned from the correlations in the gHMQC spectra. Carbon atom C7 (nitrile carbon) usually appears around δ 119. Depending on the substituent, carbon atom C1 was usually found shifted downfield around δ 130-170 (except in 4-iodobenzonitrile for which it appears around δ 100). Carbon atom C4 is shifted upfield, and was usually found around δ 100-115. Similarly, all the carbons of isomer B can be assigned.
In the five membered heterocycles, the ⁴J_H-H coupling was used together with gHMBC and NOESY1D spectroscopy to identify the major isomer. Regioisomers in the fluorine containing benzonitriles were assigned by ¹³C spectroscopy (with the help of the fact that the boron bearing carbon is not observed due to broadening from and coupling with boron). In the case of 1,3-dicyanobenzene, ¹H NMR spectroscopy was employed to assign the major and minor isomers.
Experimental Details and Spectroscopic Data EXAMPLE 1 Borylation of 4-fluorobenzonitrile

General procedure A was applied to 4-fluorobenzonitrile (242 mg, 2 mmol) and HBPin (73 μL, 64 mg, 0.5 mmol) with a reaction time of 8 h. The ratio of the two isomers in the crude reaction mixture by GC was 11:89. Kugelrohr distillation furnished a mixture of the two isomeric borylated products (88.5 mg, 72%) as a white solid. The ratio of the two isomers in the isolated product by GC was 8:92. ¹³C NMR spectroscopy was used to assign the major isomer as 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboryl)benzonitrile. ¹H NMR (CDCl₃, 500 MHz): δ (major isomer) 8.04 (dd, ⁴J_H-F=5.4 Hz, J=2.2 Hz, 1H, H_d), 7.7 (ddd, J=8.5, 2.2 Hz, ⁴J_H-F=4.9 Hz, 1H, H_e), 7.1 (t, J=8.5 Hz, 1H, H_f), 1.32 (br s, 12H), (minor isomer) 7.67 (dd, J=8.8 Hz, ⁴J_H-F=4.9 Hz, 1H, H_c), 7.52 (dd, ³J_H-F=8.5 Hz, J=2.9 Hz, 1H, H_a), 7.17 (dt, J=8.3, 2.9 Hz, 1H, H_b) 1.34 (br s, 12H); ¹³C NMR {¹H} (CDCl₃, 125 MHz): δ (major isomer) 169.0 (d, ¹J_C-F=261.3 Hz, C1′), 141.6 (d, ³J_C-F=9.6 Hz, C3′), 137.0 (d, ³J_C-F=10.5 Hz, C5′), 117.9 (nitrile C7′), 116.7 (d, ²J_C-F=25.6 Hz, C6′), 108.2 (d, ⁴J_C-F=3.8 Hz, C4′), 84.5 (C8′), 24.7 (C9′), (minor isomer) 164.2 (d, ¹J_C-F=257.1 Hz, C1), 135.9 (d, ³J_C-F=8.8 Hz, C5), 122.8 (d, ²J_C-F=21.0 Hz, C2), 118.5 (d, ²J_C-F=22.2 Hz, C6), 118.1 (nitrile C7), 113.1 (C4), 85.1 (C8), 24.7 (C9); ¹¹B NMR (CDCl₃, 96 MHz): δ 29.92; ¹⁹F NMR (CDCl₃, 282 MHz): δ (major isomer) −92.62 (m), (minor isomer) −104.84 (m); FT-IR (neat): 3076, 2982, 2934, 2231, 1608, 1487, 1429, 1412, 1373, 1350, 1236, 1143, 1070, 964, 852, 835, 571 cm⁻¹; LRMS (% rel. int.): m/e (major isomer) 247 M⁺ (26), 232 (100), 205 (12), 188 (20), (minor isomer) 247 M⁺ (29), 232 (97), 206 (100), 189 (74), 148 (97), 121 (25); Anal. Cacld for C₁₃H₁₅BFNO₂: C, 63.20; H, 6.12; N, 5.67. Found: C, 63.52; H, 6.20; N, 5.56. HRMS Calcd for C₁₃H₁₅BFNO₂: 247.1180. Found: 247.1171.





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1,6- and 1,7-Regioisomers of Asymmetric and Symmetric Perylene Bisimides

 1,6- and 1,7-Regioisomers of Asymmetric and Symmetric Perylene Bisimides

Molecules 2014, 19(1), 327-341; doi:10.3390/molecules19010327

  http://www.mdpi.com/1420-3049/19/1/327/htm

 


 






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N,N-Dimethyl-5-nitropyridin-2-amine

N,N-Dimethyl-5-nitropyridin-2-amine³⁰ (3d)

Yellow solid; mp 155-157 °C; ¹H NMR (DMSO-d₆, 400 MHz) δ 9.02 (d, 1H, J 2.8 Hz), 8.26 (dd, 1H, J 9.2; 2.8 Hz), 6.80 (d, 1H, J 9.2 Hz), 3.25 (s, 6H); IR (KBr) ν_max/cm^-1: 2924, 2854, 1597, 1335, 1295, 1118, 810; MS (CI method): 168 (M+1, 100%).

30. Heindel, N. D.; Kannewell, P. D.; Chem. Commun. 1969, 38. 

Journal of the Brazilian Chemical Society

Print version ISSN 0103-5053

J. Braz. Chem. Soc. vol.21 no.8 São Paulo  2010

http://dx.doi.org/10.1590/S0103-50532010000800005

see

http://www.scielo.br/scielo.php?pid=S0103-50532010000800005&script=sci_arttext

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2-(3-BROMOPHENYL)-6-(TRIFLUOROMETHYL)PYRAZOLO[1,5-a]PYRIDINE

2-(3-BROMOPHENYL)-6-(TRIFLUOROMETHYL)PYRAZOLO[1,5-a]PYRIDINE

The pyrazolo[1,5-a]pyridine (4) exhibits the following characteristics:

mp 59-60 °C;

IR (film) cm^-1 1647, 1460, 1334, 1321, 1157, 1112, 1076, 1052;

TLC: R_f = 0.38 (silica gel, 4:1 hexanes:ethyl acetate);

¹H NMR pdf (400 MHz, DMSO-d₆)

δ: 7.24 (s, 1 H), 7.35 (d, 1 H, J = 9.2 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 7.54 (d, 1 H, J = 8.0 Hz), 7.81 (d, 1 H, J = 9.2 Hz), 7.95 (d, 1 H, J = 8.0 Hz), 8.12 (m, 1 H), 9.26 (s, 1 H);

¹³C NMR pdf (100 MHz, DMSO-d₆)

δ: 96.3, 115.3 (q), 119.7, 122.7, 122.7, 125.4, 125.6, 128.5 (q), 129.1, 131.4, 132.1, 134.7, 142.1, 153.6;

¹⁹F NMR pdf (376 MHz, DMSO-d₆) δ: -59.73;

LRMS (ESI) m/z (%): 341 (100), 342 (25), 343 (83), 344 (17);

HRMS (FAB) m/z M⁺ calcd for C₁₄H₈BrF₃N₂: 339.9823 found: 339.9827.

Anal. Calc for C₁₄H₈BrF₃N₂: C, 49.29; H, 2.36; N, 8.21. Found: C, 49.26; H, 2.33; N, 8.11.

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NMR Spectroscopic Investigations of Mixed Aggregates Underlying Highly Enantioselective 1,2-Additions of Lithium Cyclopropylacetylide to Quinazolinones

Organolithium reagents can also perform enantioselective nucleophilic addition to carbonyl and its derivatives, often in the presence of chiral ligands. This reactivity is widely applied in the industrial syntheses of pharmaceutical compounds. An example is the Merck and Dupont synthesis of Efavirenz, a potent HIV reverse transcriptase inhibitor. Lithium acetylide is added to a prochiral ketone to yield a chiral alcohol product. The structure of the active reaction intermediate was determined by NMR spectroscopy studies in the solution state and X-ray crystallography of the solid state to be a cubic 2:2 tetramer.

Collum, D.B. et al. (2001). "NMR Spectroscopic Investigations of Mixed Aggregates Underlying Highly Enantioselective 1,2-Additions of Lithium Cyclopropylacetylide to Quinazolinones". J. Am. Chem. Soc. 123: 9135–9143. doi:10.1021/ja0105616.

The solution structures of mixed aggregates derived from lithium alkoxides and lithium acetylides were investigated as part of a program to develop practical syntheses of quinazolinone-based nonnucleoside reverse transcriptase inhibitors. Low-temperature ⁶Li, ¹³C, and ¹⁵N NMR spectroscopies reveal that mixtures of lithium cyclopropylacetylide (RCCLi), a (+)-carene-derived amino alkoxide (R*OLi), and lithium hexamethyldisilazide (LiHMDS) in THF/pentane afford a (RCCLi)₃(R*OLi) mixed tetramer, a C₂-symmetric and asymmetric (RCCLi)₂(R*OLi)₂ mixed tetramer, and a C₃-symmetric (RCCLi)(R*OLi)₃ mixed tetramer. Analogous mixtures of RCCLi/R*OLi in Et₂O and Me₂NEt also provide 3:1, 2:2, and 1:3 mixed tetramers. The stereochemistry of aggregation is highly sensitive to the medium. The C₂-symmetric (RCCLi)₂(R*OLi)₂ mixed tetramer is formed in Et₂O, whereas the asymmetric isomer is formed in Me₂NEt. LiHMDS in THF is shown to be an efficient proton scavenger without forming LiHMDS−RCCLi or LiHMDS−R*OLi mixed aggregates. LiHMDS−RCCLi mixtures form mixed aggregates in Me₂NEt.

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2D NMR contour plot of a dehydroannulene

2D NMR contour plot of a dehydroannulene
 

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