Jan M. Bakke

Rotational isomerism—22: An nmr study of oh..π bonding and the conformations of benzyl alcohol and derivatives

Abstract The conformations of benzyl alcohol, the ortho and para nitro and methoxy derivatives and benzyl methyl ether have been investigated by NMR in CCL4 and DMSO solutions. The 3J(CH.OH) and 2J(H.C.H) couplings (the latter via the 2J(H.C.D)coupling)and the OH chemical shift (in DMSO and ∞ dilXXX as conformational probes. The δ∞ (OH) for ROH (R = Me, Et, iPr) is also given. The results provide no support for the existence of an intramolecular H-bond in benzyl akohol The endo conformation of the OH proton (anti to a CH proton) is favoured by ca. 1 kcal mole−1 over the exo conformation (H anti to phenyl) and these conformers are responsible for the separate OH frequencies observed in the IR spectrum. The results do not support an extreme conformation of the phenyl ring (C.C.C.O dihedrals of 0 or 90°) but are consistent with either an 60° conformation of the phenyl ring or a freely rotating model. In ortho nitrobenzyl alcohol intramolecular H-bonding is present, but in ortho methoxy benzyl alcohol little or no bonding to the substituent occurs.

Nitropyridines: Synthesis and reactions

Reaction of pyridine and substituted pyridines with N2O5 in an organic solvent gives the N-nitropyridinium ion. When this is reacted with SO2/HSO3– in water, 3-nitropyridine is obtained (77 % yield). With substituted pyridines, the method gives good yields for 4-substituted and moderate yields for 3-substituted pyridines. The reaction mechanism is not an electrophilic aromatic substitution, but one in which the nitro group migrates from the 1-position to the 3-position by a [1,5 ] sigmatropic shift. From 4-aminopyridine, imi- dazo [4,5-c ] pyridines have been synthesized. From 3-nitropyridine, 5-nitropyridine-2-sulfonic acid is formed in a two-step reaction. From this, a series of 2-substituted-5-nitro-pyridines has been synthesized. 3-Nitropyridine and 4-substituted-3-nitropyridines have been substituted with ammonia and amines by the vicarious substitution method and by the oxidative substitution method in the position para to the nitro group. High regioselectivities and yields have been obtained in both cases to afford a series of 4-substituted-2-alkylamino-5-nitropyridines.

THE CONFORMATIONAL COMPOSITION OF 3-BUTEN-1-OL, THE IMPORTANCE OF INTRAMOLECULAR HYDROGEN BONDING

Abstract The conformations of 3-buten-1-ol ( 1 ), and its model compounds cis-6-methyl-3-cyclohexen-1-ol ( 6 ), 3-cyclopenten-1-ol ( 7 ) and epicholesterol ( 9 ) have been investigated by FT-IR and 1 H NMR spectroscopy. The energies and geometries of 1 , 6 and 7 were also investigated by molecular mechanics, semiempirical molecular orbital and ab initio calculations, while 9 was investigated by molecular mechanics only. The objective of the work was to study the conformational composition and importance of intramolecular OH… π hydrogen bonding for this composition in 1 . Only two conformers of 1 have a geometrical possibility for intramolecular hydrogen bonding: Conformers 12 and 13 ( Fig. 1 Download high-res image (157KB) Download full-size image Fig. 1 . Ball and stick models of the 14 3-buten-1-ol ( 1 ) conformers (HF/6-31G** geometries). ). Compounds 6 and 7 were used as models for Conformer 12 , while 9 was used as a model for Conformer 13 . The investigations showed that Conformer 13 is the only hydrogen-bonded conformer, and that Conformer 12 is not intramolecularly hydrogen bonded. Conformer 13 was the most populated conformer, while Conformer 12 was hardly populated. The combination of experimental and theoretical data, and the use of model compounds was found necessary to obtain this conclusion.

The oxidative amination of 3-nitropyridines

3-Nitropyridine was reacted with ammonia or alkylamines and KMnO4 under several different conditions. Substitutions in the para position to the nitro group were obtained with high regioselectivity: with ammonia, 2-amino-5-nitropyridine (66%), with butylamine, 2-butylamino-5-nitropyridine (92%), with diethylamine, 2-diethylamino-5-nitropyridine (49%). Under the same conditions, with methyl-3-nitroisonicotinoate and diethylamine/KMnO4, methyl 2-diethylamino-5-nitroisonicotinoate (48%), with 4-acetyl-3-nitropyridine (protected by ethylene glycol) 2-diethylamino-4-acetyl-5-nitropyridine (72%, protected) and with 4-cyano-3-nitropyridine, 2-amino-4-cyano-5-nitropyridine (41%) were obtained. All yields are isolated.

Rotational isomerism around the C–O bond in saturated acyclic alcohols—assignment of the experimental IR hydroxyl stretch bands using semiempirical MO and ab initio calculations

Abstract We have assessed the abilities of semiempirical MO and ab initio frequency calculations to predict the experimental IR hydroxyl stretch frequencies. It was shown that ab initio calculations using medium to large basis sets at the Hartree–Fock level semiquantitatively reproduce the experimental hydroxyl stretch frequency pattern for the simple saturated alcohols methanol, ethanol, 2-propanol and t-butyl alcohol. Furthermore we have shown this to be the case for the sterically crowded alcohol 2,2-dimethylpropanol (neopentyl alcohol).

Nucleophilic alkylations of 3-nitropyridines

3-Nitropyridine and 4-substituted-3-nitropyridines were reacted with chloroform, methyl chloroacetate and ethyl 2-chloropropionate under vicarious nucleophilic substitution (VNS) conditions. Substitution was obtained in the ortho or para position to the nitro group with acceptable to good yields and regioselectivity. With potassium 5-nitropyridine-2-sulfonate the substitution took place in the 4-position. Further substitution of the sulfonate group proved to be possible.

Substitution reactions of 5-nitropyridine-2-sulfonic acid. A new pathway to 2,5-disubstituted pyridines.

We have investigated reactions of 5-nitropyridine-2-sulfonic acid and its potassium salt in which substitution of the sulfonate group by oxygen, nitrogen and halogen nucleophiles has been attempted. By this approach, 2-methoxy- (95% yield), 2-ethoxy- (97%), 2-isopropoxy- (65%), 2-amino- (92%), 2-butylamino- (76%), 2-diethylamino- (62%), 2-ethylamino- (32%), 2-benzylamino- (77%), 2-(R-1-phenylethylamino)- (71%) and 2-chloro-5-nitropyridine (87%) have been obtained. No reactions were observed with phenols or anilines. With t-BuOH, 2-hydroxy-5-nitropyridine was formed together with 2-methylpropene.

Selective vicarious nucleophilic amination of 3-nitropyridines

Nine 3-nitropyridine compounds and 4-nitroisoquinoline have been aminated in the 6-position (for 4-nitroisoquinoline in the 1-position) by vicarious nucleophilic substitution reactions. Two amination reagents were used, hydroxylamine and 4-amino-1,2,4-triazole. The yields were from moderate to good. Use of hydroxylamine gave an easy work-up procedure by which almost pure product was obtained directly, but 4-amino-1,2,4-triazole gave better yields of the aminated product for some of the substrates. By this, a general method for the preparation of 3- or 4-substituted-2-amino-5-nitropyridines was obtained.

A new synthesis of L-ascorbic acid (vitamin C)

A new synthesis of L-ascorbic acid is described, involving a one-step oxidation of 1,2-O-isopropylidene-α-D-glucofuranose to 1,2-O-isopropylidene-α-D-xylo-hexofuranurono-6,3-lactone-5-ulose and acid treatment of the latter, followed by reduction.

Synthesis of 1,3-Dinitrotetrahydropyrimidines

Abstract Reaction of pyrimidine with dinitrogen pentoxide followed by addition of alcohol resulted in formation of 2,4-dialkoxy-l,3-dinitro-l,2,3,4-tetrahydropyrimidines.