The synthesis of amines poses a special problem because only in certain cases is the obvious disconnection successful.

The problem is that the product is usually more reactive than the starting material and there is a danger that multiple alkylation will take place.

The few successful examples you have seen so far in this chapter have been exceptions, for either steric or electronic reasons, and from now on we advise you to avoid disconnecting an amine in this way. Sometimes further alkylation is made unfavourable by the increased steric hindrance that would result: this is probably the case for the cetaben ethyl ester we made by this reaction.

If the alkylating agent contains an inductive electron-withdrawing group, the product may be less reactive than the starting material—benzylamine was only alkylated once by the alkyl bromide in the synthesis of ICI-D7114 because of the electron-withdrawing effect of the aryloxy group. What are the alternatives? There are two main ones, and both involve functional group interconversion, with the reactive amine being converted to a less reactive derivative before disconnection. The first solution is to convert the amine to an amide and then disconnect that. The reduction of amide to amine is quite reliable, so the FGI is a reason able one.

The amide reduction approach was used in a synthesis of this amine, although catalytic hydrogenation was used to reduce the amide.

The second alternative is to convert to an imine, which can be disconnected to amine plus carbonyl compound. This approach is known as reductive amination and we discussed it in detail.

Ocfentanil is an opioid painkiller that lacks the addictive properties of morphine. Disconnection of the amide gives a secondary amine that we can convert to an imine for disconnection to a ketone plus 2-fluoroaniline.

The synthesis is straightforward: a reductive amination followed by acylation of the only remaining NH group. The tertiary amine in the left-hand ring interferes with neither of these reactions.

There are several conceivable routes to the neuroactive drug fenfluramine—one analysis, which uses both the amide and the imine FGI methods, is shown below and this is the route used to make the drug. Notice that the oxime is used instead of the imine. N-unsubstituted imines are very unstable, and the much more stable—indeed isolable—oxime serves the same purpose. Oximes are generally reduced with LiAlH₄.

You should now be able to suggest a plausible analysis of the secondary amine terodilin. The structure is in the margin; write down a retrosynthetic analysis and suggested synthesis before looking at the actual synthesis below. You should find yourself quite restricted in choice: the amide route clearly works only if there is a CH₂ group next to the nitrogen (this comes from the C=O reduction), so we have to use an imine.

In the synthesis of terodilin, it was not necessary to isolate the imine—reduction of imines is faster than reduction of ketones, so formation of the imine in the presence of a mild reducing agent (usually NaCNBH₃ or catalytic hydrogenation) can give the amine directly.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم العلاقات العامة يختتم فعاليات محطات فتية الكفيل الثقافية في محافظة نينوى

ما الخدمات التي قدّمها موكب أشبال الطفّ لزائري عاشوراء؟

العتبة العباسية المقدسة تنظّم مسيرات عزائية لإحياء ذكرى عاشوراء في نينوى

قسم الشؤون الفكرية يحيي ذكرى استشهاد الإمام الحسين (عليه السلام) في القارة الإفريقية

المزيد

الآخبار الصحية

تناول الجبن.. مفيد للجسم أم خطر يهدد صحتك؟

طبيبة أسنان تحذر.. لا تتجاهل هذه العلامة بعد التنظيف

يجب أن تأكل المزيد من الشمام هذا الصيف.. إليك السبب ؟

تأثير صحي كبير.. كم بيضة يجب أن تتناول يوميا؟

المزيد

الآخبار التكنلوجية

أداء خلايا البيروفسكايت الشمسية تحت الماء قد يزيد كفاءة تحويل الكهرباء

مسافة الأمان: أساس القيادة الآمنة وتجنب الحوادث

هل القيادة السريعة تعني استهلاك اكثر للوقود؟

لماذا يعتبر كوكب المريخ غير صالح للحياة؟

المزيد

مواضيع ذات صلة

E-selective reduction of alkynes using sodium in liquid ammonia

Functional group interconversion

Multiple step syntheses: avoid chemoselectivity problems

Synthons are idealized reagents

The E-selective Wittig reaction

The Z-selective Wittig reaction

Stereoselectivity in the Wittig reaction depends on the ylid

The Peterson reaction is stereospecific

The one-step Julia olefination

The Julia olefi nation is stereoselective

The Julia olefination is regiospecific and connective

Sulfoxide elimination—oxidation to enones