Pyrrole

الأسماء
اسم أيوپاك المفضل 1H-Pyrrole
أسماء أخرى Azole Imidole
تمييز
رقم CAS	[109-97-7]
PubChem	8027
رقم EC	203-724-7
ChEBI	19203
رقم RTECS	UX9275000
SMILES	N1C=CC=C1
InChI	InChI=1/C4H5N/c1-2-4-5-3-1/h1-5H
مرجع بايلستاين	1159
مرجع Gmelin	1705
الخصائص
الصيغة الجزيئية	C4H5N
كتلة مولية	67.09 g mol-1
الكثافة	0.967 g cm−3
نقطة الانصهار	−23 °C, 250 K, -9 °F
نقطة الغليان
ضغط البخار	7 mmHg at 23 °س
الحموضة (pKa)	16.5 (لپروتون N-H)
القاعدية (pKb)	13.6 (pKa 0.4 لحمض مترافق)
القابلية المغناطيسية	-47.6·10−6 cm3/mol
اللزوجة	0.001225 Pa s
الكيمياء الحرارية
للتشكل ΔfHo298	108.2 kJ mol−1 (gas)
للاحتراق ΔcHo298	2242 kJ mol−1
سعة الحرارة النوعية، C	1.903 J K−1 mol−1
المخاطر
صفحة بيانات السلامة	Chemical Safety Data
(معيـَّن النار)
نقطة الوميض	33.33 °م (91.99 °ف; 306.48 ك)
الاشتعال الذاتي	550 °م (1,022 °ف; 823 ك)
حدود الانفجار	3.1–14.8%
مركبات ذا علاقة
مركـّبات ذات علاقة	Phosphole, arsole, bismole, stibole
ما لم يُذكر غير ذلك، البيانات المعطاة للمواد في حالاتهم العيارية (عند 25 °س [77 °ف]، 100 kPa).
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مراجع الجدول

پيرول Pyrrole هومركب عضوي أروماتي حلقي غير متجانس، وهي حلقة خماسية الأعضاء بصيغة C₄H₄NH. وهوسائل متطاير عديم اللون يقتم بمجرد تعرضه للهواء. المشتقات المُعوَّضة تُسمى، أيضاً، پيرولات، مثل N-methylpyrrole, C₄H₄NCH₃. پورفوباي‌لينوجن Porphobilinogen، الپيرول المُعوَّض ثلاثياً، هوسابق مُخـَلـَّق حيوياً للعديد من المنتجات الطبيعية مثل الهيم.

الپيرولات هي مكونات لحلقات كبرى أكثر تعقيداً، تضم پورفيرينوجنات porphyrinogen ومنتجات مشتقة منهم، مثل پورفيرينات الهيم، والكلورينات chlorin، والكلورين الجرثومي bacteriochlorins، والكلوروفيلات.

الخصائص

الپيرول هوسائل متطاير عديم اللون يتحول إلى لون قاتم بمجرد تعرضه للهواء، وعادةً ما يـُنقـَّى بالتقطير مباشرة بعد الاستخدام. الپيرول له رائحة المكسرات. وهو 5-membered aromatic heterocycle, like الـفوران furan وثيوفين thiophene. ويختلف عن فوران وثيوفين في حتى له ثنائية قطبية يقع فيها القطب الموجب بجانب ذرة غير متجانسة، بعزم ثنائي القطب قدره 1.58 د. في CDCl₃، فإن لها انزياحات كيميائية عند 6.68 (H2, H5) و6.22 (H3, H4). الپيرول حامضي بضَعف، مع حمض مترافق pK_a بقيمة −3.8. أكثر كاتيونان الپيروليوم استقرارً من حيث التحريك الحراري (C₄H₆N⁺) يتشكل بإضافة پروتون عند المسقط 2. تعويض الپيرول بمعوضات ألكيلية يعطي جزيئاً أكثر قاعدية — عملى سبيل المثال، tetramethylpyrrole له حمض مرافق pK_a قدره +3.7. كما حتى الپيرول حامضي بضَعف عند مسقط N–H، بقيمة pK_a قدرها 17.5.

التاريخ

تم التعهد على الپيرول لأول مرة من قِبل فريدليب فرديناند رونگه في 1834، كمكون لـقطران الفحم. In 1857, it was isolated from the pyrolysate of bone. Its name comes from the Greek pyrrhos (πυρρός, “reddish, fiery”), from the reaction used to detect it—the red color that it imparts to wood when moistened with حمض الهيدروكلوريك.

التواجد في الطبيعة

Pyrrole itself is not naturally occurring, but many of its derivatives are found in a variety of cofactors and natural products. Common naturally produced molecules containing pyrroles include , bile pigments like bilirubin and biliverdin, and the porphyrins of heme, chlorophyll, chlorins, bacteriochlorins, and porphyrinogens. Other pyrrole-containing secondary metabolites include PQQ, makaluvamine M, ryanodine, rhazinilam, lamellarin, prodigiosin, myrmicarin, and sceptrin. The syntheses of pyrrole-containing haemin, synthesized by Hans Fischer was recognized by the Nobel Prize.

Pyrrole is a constituent of tobacco smoke and may contribute to its toxic effects.

التخليق

Pyrrole is prepared industrially by treatment of furan with ammonia in the presence of solid acid catalysts, like and .

Pyrrole can also be formed by catalytic dehydrogenation of pyrrolidine.

السبل المعملية

Several syntheses of the pyrrole ring have been described.

تخليق پيرول هانتش

تخليق پيرول هانتش هوتفاعل β-ketoesters (1) مع الأمونيا (أوأمينات رئيسية) وα-haloketones ‏(2) لإعطاء پيرولات معوَّضة (3).

تخليق پيرول كنور

The Knorr pyrrole synthesis involves the reaction of an α-amino ketone or an α-amino-β-ketoester with an activated methylene compound. The method involves the reaction of an α-aminoketone (1) and a compound containing a methylene group α to (bonded to the next carbon to) a carbonyl group (2).

تخليق پيرول پال-كنور

In the Paal–Knorr pyrrole synthesis, a 1,4-dicarbonyl compound reacts with ammonia or a primary amine to form a substituted pyrrole.

تفاعل ڤان لويزن

The Van Leusen reaction can be used to form pyrroles, by reaction of tosylmethyl isocyanide (TosMIC) with an enone in the presence of base, in a Michael addition. A 5-endo cyclization then forms the 5-membered ring, which reacts to eliminate the tosyl group. The last step is tautomerization to the pyrrole.^[]

تخليق بارتون-زارد

The Barton–Zard synthesis proceeds in a manner similar to the Van Leusen synthesis. An isocyanoacetate reacts with a nitroalkene in a 1,4-addition, followed by 5-endo-dig cyclization, elimination of the nitro group, and tautomerization.

تخليق پيرول پيلوتي-روبنسون

مواد البداية في تخليق پيرول پيلوتي-روبنسون، المسماة على اسمي گرترود وروبرت روبنسون وأوسكار پيلوتي، هي مكافئان للألدهايد والهيدرازين. الناتج هوپيرول بمعوضين عند المسقطين ثلاثة و4. The aldehyde reacts with the diamine to an intermediate di-imine (R–C=N−N=C–R). In the second step, a [3,3]-sigmatropic rearrangement takes place between. Addition of hydrochloric acid leads to ring closure and loss of ammonia to form the pyrrole. The mechanism was developed by the Robinsons.

In one modification, propionaldehyde is treated first with hydrazine and then with benzoyl chloride at high temperatures and assisted by microwave irradiation:

السبل المبنية على الإضافة الحلقية

Pyrroles bearing multiple substituents are obtained from the reaction of münchnones and alkynes. The reaction mechanism involves 1,3-dipolar cycloaddition followed by loss of carbon dioxide by a retro-Diels–Alder process. Similar reactions can be performed using azalactones.

Pyrroles can be prepared by silver-catalyzed cyclization of alkynes with isonitriles, where R² is an electron-withdrawing group, and R¹ is an alkane, aryl group, or ester. Examples of disubstituted alkynes have also been seen to form the desired pyrrole in considerable yield. The reaction is proposed to proceed via a silver acetylide intermediate. This method is analogous to the azide–alkyne click chemistry used to form azoles.

وسائل أخرى

One synthetic route to pyrrole involves the decarboxylation of ammonium mucate, the ammonium salt of mucic acid. The salt is typically heated in a distillation setup with glycerol as a solvent.

التخليق الحيوي للپيرولات

The de novo biosynthesis of pyrrole rings begins with aminolevulinic acid (ALA), which is synthesized from glycine and succinyl-CoA. ALA dehydratase catalyzes the condensation of two ALA molecules via a Knorr-type ring synthesis to form porphobilinogen (PBG). This later reacts to form, for example, the macrocycles heme and chlorophyll.

.

Proline is biosynthetically derived from the amino acid L-glutamate. Glutamate-5-semialdehyde is first formed by glutamate 5-kinase (ATP-dependent) and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH). This can then either spontaneously cyclize to form 1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase (using NADH or NADPH), or turned into ornithine by ornithine aminotransferase, followed by cyclisation by ornithine cyclodeaminase to form proline.

Proline can be used as precursor of aromatic pyrroles in secondary natural products, as in prodigiosins.

The biosynthesis of Prodigiosin involves the convergent coupling of three pyrrole type rings (labeled A, B, and C in figure 1) from L-proline, L-Serine, L-methionine, pyruvate, and 2-octenal.

Ring A is synthesized from L-proline through the nonribosomal peptide synthase (NRPS) pathway (figure 2), wherein the pyrrolidine ring of proline is oxidized twice through FAD+ to yield pyrrole ring A.

Ring A is then expanded via the polyketide synthase pathway to incorporate L-serine into ring B (figure 3). Ring A fragment is transferred from the peptidyl carrier protein (PCP) to the Acyl Carrier Protein (ACP) by a KS domain, followed by transfer to malonyl-ACP via decarboxylative Claisen condensation. This fragment is then able to react with the masked carbanion formed from the PLP mediated decarboxylation of L-Serine, which cyclizes in a dehydration reaction to yield the second pyrrole ring. This intermediate is then modified by methylation (which incorporates a methyl group from L-methionine onto the alcohol at theستة position) and oxidation of the primary alcohol to the aldehyde to yield the core A-B ring structures.

التفاعلات وردود الأفعال

Due to its aromatic character, pyrrole is difficult to hydrogenate, does not easily react as a diene in Diels–Alder reactions, and does not undergo usual olefin reactions. Its reactivity is similar to that of benzene and aniline, in that it is easy to alkylate and acylate. Under acidic conditions, pyrroles polymerize easily, and thus many electrophilic reagents that are used in benzene chemistry are not applicable to pyrroles. In contrast, substituted pyrroles (including protected pyrroles) have been used in a broad range of transformations.

تفاعل الپيرول مع محبي الإلكترونات

Pyrroles generally react with electrophiles at the α position (C2 or C5), due to the highest degree of stability of the protonated intermediate.

Pyrroles react easily with nitrating (e.g. /O), sulfonating (), and halogenating (e.g. NCS, NBS, , , and KI/) agents. Halogenation generally provides polyhalogenated pyrroles, but monohalogenation can be performed. As is typical for electrophilic additions to pyrroles, halogenation generally occurs at the 2-position, but can also occur at the 3-position by silation of the nitrogen. This is a useful method for further functionalization of the generally less reactive 3-position.^[]

أسيـَلة

أسيـَلة Acylation تحدث عموماً عند the 2-position, through the use of various methods. Acylation with acid anhydrides and acid chlorides can occur without a catalyst; alternatively, a Lewis acid may be used. 2-Acylpyrroles are also obtained from reaction with nitriles, by the Houben–Hoesch reaction. Pyrrole aldehydes can be formed by a تفاعل فيلزماير-هاك. N-Acylation of simple pyrrole does not occur.

ألكلة

الألكلة المحبة للإلكترونات للپيرول البسيط هي غير شائعة. الألكلة Alkylation لتشكيل إنونات enones عند C2 قد شوهدت.

تفاعل الپيرول منزوع الپروتون

The NH proton in pyrroles is moderately acidic with a of 16.5. Pyrrole can be deprotonated with strong bases such as butyllithium and sodium hydride. The resulting alkali pyrrolide is nucleophilic. Treating this conjugate base with an electrophile such as iodomethane gives N-methylpyrrole. N-Metalated pyrrole can react with electrophiles at the N or C positions, depending on the coordinating metal. More ionic nitrogen–metal bonds (such as with Li, Na, and K) and more solvating solvents lead to N-alkylation. Nitrophilic metals, such as MgX, lead to alkylation at C (mainly C2), due to a higher degree of coordination to the nitrogen atom. In the cases of N-substituted pyrroles, metalation of the carbons is more facile. Alkyl groups can be introduced as electrophiles, or by cross-coupling reactions.^[]

Substitution at C3 can be achieved through the use of N-substituted 3-bromopyrrole, which can be synthesized by bromination of N-silylpyrrole with NBS.^[]

الاختزالات

Pyrroles can undergo reductions to pyrrolidines and to pyrrolines. For example, Birch reduction of pyrrole esters and amides produced pyrrolines, with the regioselectivity depending on the position of the electron-withdrawing group.^[]

Cyclization reactions

Pyrroles with N-substitution can undergo cycloaddition reactions such as [4+2]-, [2+2]-, and [2+1]-cyclizations. Diels-Alder cyclizations can occur with the pyrrole acting as a diene, especially in the presence of an electron-withdrawing group on the nitrogen. Vinylpyrroles can also act as dienes.^[]

Pyrroles can react with carbenes, such as dichlorocarbene, in a [2+1]-cycloaddition. With dichlorocarbene, a dichlorocyclopropane intermediate is formed, which breaks down to form 3-chloropyridine (the Ciamician–Dennstedt rearrangement).

الاستخدامات التجارية

Pyrrole is a precursor to the drug tolmetin. Polypyrrole is of some commercial value. N-Methylpyrrole is a precursor to N-methylpyrrolecarboxylic acid, a building-block in pharmaceutical chemistry. Pyrroles are also found in several drugs, including atorvastatin, ketorolac, and sunitinib. Pyrroles are used as lightfast red, scarlet, and carmine pigments.

المضاهيات والمشتقات

Structural analogs of pyrrole include:

• Pyrroline, a partially saturated analog with one double bond
• Pyrrolidine, the saturated hydrogenated analog

Derivatives of pyrrole include indole, a derivative with a fused benzene ring.

انظر أيضاً

• Simple aromatic rings
• Tetrapyrrole
• Polypyrrole
• Azonine

المراجع

للاستزادة

• Jones, R. Jones, ed. (1990). Pyrroles. Part I. The Synthesis and the Physical and Chemical Aspects of the Pyrrole Ring. Recueil des Travaux Chimiques des Pays-Bas. The Chemistry of Heterocyclic Compounds. 48. Chichester: John Wiley & Sons. p. 351. doi:10.1002/recl.19911100712. ISBN .
• Jolicoeur, Benoit; Chapman, Erin E.; Thompson, Alison; Lubell, William D. (2006). "Pyrrole protection". Tetrahedron. 62 (50): 11531–11563. doi:10.1016/j.tet.2006.08.071.

وصلات خارجية

• Synthesis of pyrroles (overview of recent methods)
• Substitution reaction mechanisms of nitrogen-containing heteroaromatics