Putting more nitrogen atoms in a six-membered ring

six-membered aromatic heterocycles with two nitrogen atoms—pyridazine, pyrimidine, and pyrazine. In these compounds both nitrogen atoms must be of the pyridine sort, with lone pair electrons not delocalized round the ring. We are going to look at these compounds briefly here. Pyrimidine is more important than either of the others because of its involvement in DNA and RNA. All three compounds are very weak bases—hardly basic at all in fact. Pyridazine is slightly more basic than the other two because the two adjacent lone pairs repel each other and make the molecule more nucleophilic. The chemistry of these very electron-defi cientrings mostly concerns nucleophilic attack and displacement of leaving groups such as Cl by nucleophiles such as alcohols and amines. To introduce this subject we need to take one heterocyclic synthesis at this point, although these are properly the subject of the next chapter. The compound maleic hydrazide has been known for some time because it is easily formed when hydrazine is acylated twice by maleic anhydride.

The compound actually prefers to exist as the second tautomer (in the green frame). Reaction with POCl₃ in the way we have seen for pyridine gives the undoubtedly aromatic pyridazine dichloride. Now we come to the point. Each of these chlorides can be displaced in turn with an oxygen or nitrogen nucleophile. Only one chloride is displaced in the first reaction, if that is required, and then the second can be displaced with a different nucleophile.

How is this possible? The mechanism of the reactions is addition to the pyridazine ring followed by loss of the leaving group. When the second nucleophile attacks it is forced to attack a less electrophilic ring. An electron-withdrawing group (Cl) has been replaced by a strongly electron-donating group (NH₂) so the rate-determining step, the addition of the nucleophile, is slower.

The same principle applies to other easily made symmetrical dichloro derivatives of these rings and their benzo analogues. The nitrogen atoms can be related 1,2, 1,3, or 1,4, as in these examples. The first two are used to link the quinine-derived ligands required for the Sharpless asymmetric dihydroxylation .

اخر الاخبار

اخبار العتبة العباسية المقدسة

أهالي كربلاء يحيون اليوم السابع لذكرى شهادة الإمام الحسين (عليه السلام)

مشروع أمير القراء الوطني يشهد مشاركة أكثر من 100 طالبٍ في مرحلته الثالثة

قسم الشؤون الفكرية يصدر دليلًا يوثّق القصص الفائزة في مسابقة فتوى الدفاع المقدسة

قسم الشؤون الفكرية يعلن عن توفير عددٍ من المكتبات الإلكترونية المتخصّصة للمؤسّسات الدينية والمكتبات العامّة

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

There are thousands more heterocycles out there

Fusing rings to pyridines: quinolines and isoquinolines

Benzo-fused heterocycles-Indoles are benzo-fused pyrroles

Five-membered rings with two or more nitrogen atoms Imidazole

Nitrogen anions can be easily made from pyrrole

Five-membered heterocycles act as dienes in Diels–Alder reactions

Electrophilic addition may be preferred to substitution with furan

Furan and thiophene are oxygen and sulfur analogues of pyrrole

Five-membered aromatic heterocycles are good at electrophilic substitution

Pyridine as a catalyst and reagent

Pyridine N-oxides are reactive towards both electrophilic and nucleophilic substitution

Pyridones are good substrates for nucleophilic substitution