Determining stereochemistry when coupling constants are no help: the nuclear Overhauser effect

The coupling constant between the green protons of the compound below is rather large, at 11 Hz—about the same as the trans diaxial coupling in a cyclohexane. The Karplus relationship suggests the green protons must therefore spend much of their time with their bonds arranged with a dihedral angle close to 180°, and from this we can deduce that the compound has the conformation, as well as the configuration, shown. A more difficult problem is the assignment of the stereochemistry of the elimination product from this bromoamine and base. It’s not a simple question, because the elimination also involves rearrangement of the amino group. The product is an alkene with two possible geometries.

Usually we would use coupling constants to determine alkene geometry, but they are no use here as there is only one proton on the alkene: it will be a singlet in both compounds. In such cases, we can make use of a quirk of NMR known as the nuclear Overhauser effect (NOE). NOE is rather different from coupling in the information it provides: it tells us which hydrogens are close in space rather than their relationship through bonds as revealed by coupling constants. The details of the origin of the nuclear Overhauser effect are beyond the scope of this book, but we can give you a general idea of what the effect is. As you learned, when a proton NMR spectrum is acquired, a pulse of radio frequency electromagnetic radiation jolts the spins of the protons in the molecule into a higher energy state. The signal we observe is generated by those spins dropping back to their original states. So far, we have assumed that the drop back down is spontaneous, just like a rock falling off a cliff. In fact it isn’t—something needs to ‘help’ the protons to drop back again—a process called relaxation. And that ‘something’ is other nearby magnetically active nuclei—usually more protons. Notice nearby—nearby in space not through bonds. With protons, relaxation is always fast, and the number of nearby protons does not affect the appearance of the NMR spectrum. Although in a normal spectrum peak intensity is independent of the number of nearby protons, by using methods whose description is beyond the scope of this book it is possible to modify the intensity of the peaks very slightly according to the number of protons that are nearby. The basis of the method is that certain protons (or groups of identical protons) are irradiated selectively (in other words, they are jolted into their high energy state and held there by a pulse of radiation at exactly the right frequency—not the broad pulse needed in a normal NMR experiment). Under the conditions of the experiment, this causes protons that were relying on those irradiated protons to relax them to appear as a slightly more intense (by maybe just a few per cent) peak in the NMR spectrum. This effect is known as the nuclear Overhauser effect, and the increase in intensity of the peak the nuclear Overhauser enhance ment. Both are shortened to ‘NOE’.

All you need to be aware of at this stage is that irradiating protons in an NOE experiment gives rise to enhancements at other protons that are nearby in space—no coupling is required, and NOE is not a through-bond phenomenon. The effect also drops off very rapidly: the degree of enhancement is proportional to 1/r6 (where r is the distance between the protons) so moving two protons twice as far apart decreases the enhancement one can give to the other by a factor of 64. NOE spectra are usually presented as differences: the enhanced spectrum minus the unenhanced, so that the small enhancements of intensity in the peaks of certain protons can be spotted immediately. Applying NOE to the problem in hand solves the structure. If the protons next to the nitrogen atom in the piperidine ring are irradiated, the signal for the alkene proton increases in intensity, so these two groups of protons must be near in space. The compound is the E alkene.

Data from NOE experiments nicely supplement information from coupling constants in the determination of three-dimensional stereochemistry too. Reduction of this bicyclic ketone with a bulky hydride reducing agent gives one diastereoisomer of the alcohol, but which? Irradiation of the proton next to the OH group leads to an NOE to the green proton. This suggests that the two protons are on the same side of the molecule and that reduction has occurred by hydride delivery to the face of the ketone opposite the two methyl groups on the three-membered ring.

A combination of coupling constants and NOE effects is routinely used to assign the stereo chemistry of reaction products.

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لليوم الرابع.. قسم العلاقات العامة يواصل إقامة فعاليات مخيّم البذرة الواعدة

العتبة العباسية المقدسة تطلق التشغيل التجريبي لمعمل غسيل السجاد والأغطية

المزيد

الآخبار الصحية

نصائح عملية للحد من التعرق المفرط في الصيف

أطباء يحذرون: مكمل غذائي شائع قد يدمر الجهاز العصبي

تحذير طبي من تأثير جانبي "غير متوقع" لحقن التخسيس

حمامات الثلج قد تكون خطيرة وأحيانا مميتة.. ما السبب؟

المزيد

الآخبار التكنلوجية

أكبر جدارية شمسية في العالم تدخل موسوعة غينيس.. مشروع ضخم

تسارع دوران الأرض يثير القلق.. وتحذيرات من "كوارث محتملة" ؟

"سوذبيز" تطرح أكبر قطعة من المريخ على الأرض في مزاد علني

أوبن أيه آي تعتزم إطلاق متصفح إنترنت يعمل بالذكاء الاصطناعي

المزيد

مواضيع ذات صلة

Baldwin’s rules and ring opening

Combatting ΔS‡—the Thorpe–Ingold effect

Thermodynamic control over ring size

Making heterocycles: ring-closing reactions

Related effects in other types of compounds

Some substituents of saturated heterocycles prefer to be axial: the anomeric effect

Oxygen heterocycles

Aziridine: ring strain promotes ring opening

Reactions of saturated heterocycles

More heteroatoms in fused rings mean more choice in synthesis

Quinolones also come from anilines by cyclization to an ortho position

Quinolines and isoquinolines