CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

Subject Chemistry

Paper No and Title Paper 5: Organic Chemistry-2 (Reaction mechanism- 1) Module No and Title 9, Reactive intermediates: Carbenes and Nitrenes

Module Tag CHE_P5_M9

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

TABLE OF CONTENTS

1. Learning Outcomes 2. Carbenes

(A) Structure

(B) Reactivity of Carbenes (C) Generation of Carbenes (D) Reactions Involving Carbenes (E) Behaviour of Methylene (F) Carbenes: Illusion or Reality 3. Nitrenes

(A) Nitrenes: Basic Definition

(B) Significant Differences Between Carbenes and Nitrenes (C) Reactions Involving Nitrene as an Intermidiate

4. Summary

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

1. LEARNING OUTCOMES

After studying this module, you shall be able to

 Identify the basic structure of carbenes and nitrenes

 Know about the methods of generation of carbenes and nitrenes

 Evaluate reactivities of both carbenes and nitrenes

 Learn about important named reactions using carbenes and nitrenes to yield products of industrial and chemical importance

2. CARBENES

Methylene CH2 can be considered as the first member of an alkene series. Methylene as a highly reactive, transient molecule was first proposed in 1930 (Paneth technique – removal of metallic mirrors). Its existence as a definite intermediate in certain reactions was proved in 1959 by spectroscopic methods. Not only CH2 but RCH, R2C type of carbenes have been investigated. Carbene chemistry was one of the topics most intensely studied during 1950-1960 and again between 1990-94. The word carbene is used for methylene and as a general term for all similar compounds.

(a.) Structure

Carbenes are highly reactive species, and practically all have lifetimes considerably < 1 s.

With exceptions noted below, carbenes have been isolated only by entrapment in matrices at low temperatures (77 K or less). Carbenes are divalent carbon compounds with two non-bonding electrons on one carbon (In all six electrons on carbon). The nature of bonding in carbenes has been analysed by molecular orbital calculations (many approaches). Two important possibilities are:

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

The two nonbonded electrons of a carbene can be either paired or unpaired. If they are paired, the species is spectrally a singlet, while, two unpaired electrons appear as a triplet.

The designations singlet state and triplet state refer to molecular electronic states. In singlet carbene the carbon is sp² hybridized, the non-bonding electrons have anti-parallel spin i.e. the electrons are paired. Triplet carbene has two unpaired electrons. The carbene centre is sp hybridized in triplet carbene. The non-bonding electrons have parallel spins in different orbitals. The ground state energy difference between (CH2)S and (CH2)T is calculated to be about 10 Kcal/mole.

On the basis of the above one can say singlet methylene should be diamagnetic and triplet methylene be paramagnetic – a diradical.

Alkyl and dialkyl carbenes are generally triplets. Substituents carbene of electron pair donor ability tend to stabilise the singlet state by electron release into the vacant orbital.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

(b.) Reactivity of carbenes:

Carbenes being electron deficient molecules are generally electrophilic. Singlet carbene is more like an electrophilic species (R3C⁺, CO and isocyanides). Triplet carbenes should behave like a radical.

Both singlet and triplet carbenes are very reactive. Most of them are generated in situ.

There are no useful solvents to be used as media. They cannot be isolated but their formation/involvement can be demonstrated by product analysis.

Most reactions are carried out in gas phase or liquid phase. Reaction involving free carbenes are highly exothermic. All reactions of carbenes are generally fast (low activation energy).

(c.) Generation of Carbenes:

 Diazoalkanes are readily decomposed to carbenes by copper salts and other transition metal ions. The products of the overall reaction are the same as obtained by direct photolysis. The general evidence suggest that an adduct of the metal ion and carbene is involved. The adduct can be represented as:

In this way the complexes can be treated as metal stabilised carbenes.

A distinction is generally made between free carbenes and metal ion complexes. This latter type are spoken as carbenoids. For example carbene generated by photothesis of diazomethane is a free carbene. The copper ion catalysed reaction leads to carbene coordinated to the metal (carbenoid).

 There are numerous examples of carbene generation:

A. Isopolar approach – Photolysis, pyrolysis, transition metal ion catalysis

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

B. Polar approach – α Eliminations A. Isopolar approach

Alkyl, aryl and acyl substituted carbenes from diazo compounds.

B. Polar Approach: Generation of carbenes viz. a-Elimination [1, 1-E]

These (1 and 2) type of reactions are not applicable if there is  hydrogen present because α (E2) elimination becomes the preferred reaction.

(C) Decarboxylation of trihaloacetates in aprotic solvents.

(D) Thermolysis or pyrolysis of trihalomethyl mercury compounds

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

These mercury halides are covalent, stable at r.t.

(E) Trichloromethyl trihalosilane :

These methods permit ready formation of carbenes in near neutral media

(F) Preparation of carbenes from carbonyl compounds. This is a useful method to prepare carbenes from readily available carbonyl compounds.

(a) An aldehyde or a ketone is converted to a p-toluene sulphonyl hydrazone (Tosylhydrazone)

(b) The tosyl hydrazone is treated with a 1 eq. of base at low temperature (NaOCH3) to form a salt of hydrazine

The reaction consists of three steps.

(c) The salt is decomposed in two ways (i) UV light (ii) heat (> 130 ⁰C)

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

An aprotic solvent such as DMSO, diglyme are essential to prevent carbanion reactions

The carbene generated leads to products. This method avoids handling dangerous diazoalkanes.

Example:

The first two compounds are formed as a result of hydrogen migration and the third by C- H bond insertion of the CH3 group.

(D) Reactions Involving Carbenes

a) Addition to double bonds and triple bonds b) Insertion into C – H bonds and other bonds c) Rearrangements.

The outcome of the overall reaction depends on the mode of formation, the Singlet, triplet nature of the carbene.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

Examples:

(E) Behaviour of Methylene (CH2)

The chemical behaviour of ‘CH2’ is highly dependent on 1. The reagent (precursor) from which it is generated.

2. The wavelength of UV light used.

3. Whether the reactions are carried out in the liq. Phase or gas phase.

4. Whether the reactions are carried out in the presence of inert gas like Nitrogen, argon, CO2; or gas like O2.

The situation is complex and there are disagreement as to the exact interpretation of the facts.

Methylene itself is the most indiscriminate reagent known in organic chemistry. It shows addition to double bond, triple bond and even adds on to benzene and insertion into C-H bonds.

Example: Pay attention to the following examples.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

Explanation:

View No. 1: Hot methylene (High Energy) high reactivity low selectivity; low energy, low reactivity high selectivity.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

View No. 2: Singlet methylene and triplet methylene.

Skell Hypothesis: Singlet carbene reacts in a single concerted step and triplet carbene reacts in a two-step radical pathway

These hypothesis are applicable both to addition as well as insertion reactions.

Mechanism of addition by singlet carbene

In this pathway, spin inversion and bond inversion are postulated. The difficulty here is that there is no way to predict which process is fast or slow.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

General conclusions regarding reactivity of carbenes:

 Intermolecular and intramolecular additions and insertions can occur. However,

 Where there is a possibility of intramolecular reaction intermolecular reactions may not occur.

 Intramolecular insertion reactions one more selective. The proximity of C-H bond to the carbene center plays a major role in determining the product distribution.

Addition reactions are 10 times faster than insertion into bonds.

(F) Carbenes: Illusion or Reality

Carbenes are postulated reactive intermediates which are known to chemists. But no carbene was ever isolated and its properties studied till 1911. In that year, one French chemistry Arduengo working in DuPont laboratory (USA) reported the preparation and properties of a stable “bottleable” carbene.

This carbene derivative has an imidazole ring and two bulky adamantine rings linked to nitrogen. It crystallises from toluene as colourless rectangular solid melting point 240- 241⁰C. It is stable in the absence of oxygen and moisture. It has been fully characterised by elemental analysis (C, H, N), IR and NHR spectra and by single-crystal x-ray diffraction.

Several other type of stable carbenes have been prepared, and studied. Thus, the existence of carbenes is real and not a myth.

Selected reactions involving carbenes and carbenoids as intermediates.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

6. Synthesis of cyclopropanes: This is a useful reaction in organic synthesis.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

A good method of adding CH2 unit to an alkene to give cyclopropane is to use CH2I2 + (Zn-Cu). This method is commonly known as Simmons-smith reaction. The active step is believed to be I + ZnCH2I. Free CH2 is not involved. Simmons-smith reaction has charge scope, wide applicability and many functional groups can be present in the alkene. In preparation procedures where a CH2 is to be added to a double bond to form cyclopropane, free methylene is not used, some other method which does not the (reactive) methylene itself.

3. NITRENES

(A) Nitrene: Basic Definition

Nitrenes (R-N), are the nitrogen analogues of carbenes, and most of the comments about carbenes also applies to them. Nitrenes are too reactive for isolation under ordinary conditions, although ab initio calculations show that nitrenes are more stable than carbenes with an enthalpy difference of 25–26 kcal mol^-1 (104.7–108.8 kJ mol^-1).

General structure of a nitrene

(R=H, alkyl). Such species are also called azenes, imidogen, imene, azacarbene. Nitrenes are postulated inter mediates in certain reactions (1913)

(B) Significant Differences Between Carbenes and Nitrenes:

(A) Electronic states:

(B) Methods of Generation.

(1.) From azides: The most common method of forming nitrenes is photolytic or thermal decomposition of azides.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

This is an example of . Elimination. This method is not general. And of very limited application.

(2.) Oxidation – Reduction methods:

Here, the great ability of phosphorous to combine with oxygen is the driving force for the reaction.

Note: This is not similar to the method in carbene chemistry.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

(C) Generalised reaction of nitrenes.

Examples:

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

(C ) Reactions Involving Nitrene as an Intermidiate:

There are a few examples of reactions which involves a nitrene as intermediate. These are:

Curtius Reaction: The Curtius Rearrangement is the thermal decomposition of carboxylic azides to produce an isocyanate. These intermediates may be isolated, or their corresponding reaction or hydrolysis products may be obtained.

The reaction sequence - including subsequent reaction with water which leads to amines - is named the Curtius Reaction. This reaction is similar to the Schmidt Reaction with acids, differing in that the acyl azide in the present case is prepared from the acyl halide and an azide salt.

Hoffman reaction: The Hofmann reaction involves the conversion of carboxylic primary amides to primary amines or their derivatives. Generally, alkaline hypohalites or a combination of halogens and alkaline hydroxides are used in aqueous solutions. The rearrangement generally occurs by heating. The Hofmann reaction is applicable to the preparation of a wide variety of aliphatic, aromatic and heterocyclic amines, and is suitable for large-scale preparative work, since it is safe and relatively inexpensive to carry out, especially when chlorine and sodium hydroxide can be used.

CHEMISTRY PAPER : 5 ,Organic Chemistry- II (Reaction Mechanism-1) MODULE :9 Reactive intermediates: Carbenes and

Nitrenes

Schmidt Reaction: The Schmidt reaction is the name given to a group of reactions which involve the addition of hydrazoic acid to carboxylic acids, ketones and aldehydes, alcohols and alkenes under strongly acidic conditions.

5. Summary

In this module, we have taught you that:

 Carbenes are highly reactive species, and practically all have lifetimes considerably < 1 s. With exceptions noted below, carbenes have been isolated only by entrapment in matrices at low temperatures (77 K or less).

 The two nonbonded electrons of a carbene can be either paired or unpaired. If they are paired, the species is spectrally a singlet, while, two unpaired electrons appear as a triplet.

 The generation and reactivity of carbenes have been studied in detail with polar and isopolar approaches having being discussed in detail.

 Reactions involving carbenes have been studied which include Addition to double bonds and triple bonds, Insertion into C – H bonds and other bonds, Rearrangements.

 Many important reactions involving carbenes as intermediates have been thoroughly discussed.

 Nitrenes (R-N), are the nitrogen analogues of carbenes, and most of the comments about carbenes also applies to them.

 Nitrenes differ from carbenes in terms of electronic states and generalised reactions.

 Important named reactions such as Curtius, Schmidt and Hoffman reactions have been discussed which involve nitrene as an intremidiate.