Quinolones also come from anilines by cyclization to an ortho position

The usual method for making quinolone antibiotics is possible because they all have a carboxylic acid in the 3-position. The disconnection we used for quinoline suggests a rather unstable malonic ester derivative as starting material.

In fact, the enol ether of this compound is easily made from diethyl malonate and ethyl orthoformate [HC(OEt)₃]. The aromatic amine reacts with this compound by an addition elimination sequence, giving an enamine that cyclizes on heating. This time the geometry of the enamine is not a concern.

For examples of quinolone antibiotics we can choose ofloxacin, whose synthesis was dis cussed in detail , and rosoxacin, whose synthesis is discussed below. Both mole cules contain the same quinolone carboxylic acid framework, outlined in black, with another heterocyclic system at position 7 and various other substituents here and there.

To make rosoxacin two heterocyclic systems must be constructed. Workers at the pharmaceutical company Sterling decided to build the pyridine in an ingenious version of the Hantzsch synthesis using acetylenic esters on 3-nitrobenzaldehyde. The ammonia was added as ammonium acetate. Oxidation with nitric acid made the pyridine, hydrolysis of the esters and decarboxylation removed the acid groups, and reduction with Fe(II) and HCl converted the nitro group into the amino group required for the quinolone synthesis.

Now the quinolone synthesis can be executed with the same reagents we used before and all that remains is ester hydrolysis and alkylation at nitrogen. Notice that the quinolone cyclization could in theory have occurred in two ways as the two positions ortho to the amino group are different. In practice cyclization occurs away from the pyridine ring as the alternative quinolone would be impossibly crowded.

Since quinolones, like pyridones, can be converted into chloro-compounds with POCl₃, they can be used in nucleophilic substitution reactions to build up more complex quinolines.

We will give just one important synthesis of isoquinolines here. It is a synthesis of a dihydro isoquinoline by what amounts to an intramolecular Vilsmeier reaction in which the electrophile is made from an amide and POCl₃. Oxidation (in this case a dehydrogena tion with Pd(0)) gives the quinoline.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشعائر يواصل تحضيراته لتنظيم عمل المواكب الحسينية في زيارة الأربعين

قسم شؤون المعارف يناقش تحضيرات المؤتمر العلمي الأول لمركز تراث البصرة

قسم الشؤون الفكرية يقيم دورة تطويرية لملاكات هيأة المساءلة والعدالة في الأرشفة الإلكترونية

المجمع العلمي ينظم مجلس عزاء في قضاء الهندية

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

Aziridine: ring strain promotes ring opening

Reactions of saturated heterocycles

More heteroatoms in fused rings mean more choice in synthesis

Quinolines and isoquinolines

Pyrimidines can be made from 1,3-dicarbonyl compounds and amidines

Pyrazoles and pyridazines from hydrazine and dicarbonyl compounds

Thermodynamics is on our side

There are thousands more heterocycles out there

Fusing rings to pyridines: quinolines and isoquinolines

Putting more nitrogen atoms in a six-membered ring

Benzo-fused heterocycles-Indoles are benzo-fused pyrroles

Five-membered rings with two or more nitrogen atoms Imidazole