Carbenes and Nitrenes Flashcards
Define a carbene
Neutral divalent carbon species
6 e- around the central atom
Highly reactive
Generally electrophillic
What are the two types of carbene?
Singlet and triplet
What is a singlet carbene?
3 e- pairs and an empty p orbital around central atom
Bent structure with bp and lp in sp2 orbitals
What is the bond angle of singlet carbenes?
100-110°
What is a triplet carbene?
Two unpaired electrons (paramagnetic)
Non-linear bent strucutre
What is the bond angles in triplet carbenes?
130-150°
When are singlet/triplet carbenes most common?
Singlet - more stable in aqueous media
Triplet - more stable in the gaseous state
Why are triplet carbenes bent?
If linear then unpaired e- have no s character so less stable
Bending allows for some s character
However repulsion energy prevents more bending
When are singlets or triplets found wrt orbital energy?
Small energy gap between σ and p-orbitals then triplet
If large then singlet
What is the state of a heteroatom carbene?
Singlet ground state
Due to delocalisation of lone pair to empty p-orbital
What is the ranking of carbene stability?
Most stable: N-heterocyclic carbenes (nucleophillic), then singlet ground states, triplet ground state
The more e- donation the more stable
What type of carbene is made due to irradiation?
Usually singletexcited state
How can singlet carbenes be made?
Heating diazo or diazirine compounds
Relaxation to triplet state can occur though
How can a triplet state carbene be made via irradiation?
Using a triplet sensitier
What is a diazirine and how are they made?
Made from ketones via :
oximation (to oxime)
tosylation
NH3 to diaziridines (with single N-N)
Jones oxidation (CrO3 and H2SO4)
What is the conditions for oximation of a ketone to an oxime?
NH2OH, HCl, and Pyridine
What are the conditions for tosylation of oximes?
TsCl and NEt3
How is a diazo compound synthesised?
Synthesised from corresponding amine with HNO2 (nitrous acid)
What are the general reactions of carbenes?
Insertion into C-H bonds
Skeletal rearrangements
Additions to double bonds
Reactivity depends on substituent - if donate then carbene is not electrophillic
What is the Bamford-Stevens reaction?
Tosylhydrazones to alkene upon treatement with a strong base
Intermediate diazo compound can be isolated, this then forms carbene after heat
Carbenes only formed in aprotic solvents
What is the Shapiro reaction?
Treatment of tosylhydrazones with 2 equivalents of alkyllithium to form alkenes
Electrophile e.g. H+, RCHO etc can be added to alkene
What determines if the bamford-stevens or shapiro reaction occurs?
Bamford-stevens uses only one equivalent of alkyllithium
Shaprio reaction uses two equivalents of alkyllithium
What is Schlosser’s base?
n-BuLi and t-BuOK
Very strong base which can be used to produce a carbenoid (CR2LiCl) from CR2HLi
What occurs to alkynes at high temperatures?
R-C≡C-H ⇔ (RH)C=C:
Eqm lies to the alkyne side
What TM carbenoid is equivalent to a carbene?
Rhodium carbenoid (as it reduces reactivity)
What occurs in the Wolff rearrangment?
α-diazo ketone to a ketene
Uses Ag(I) catalyst to aid N2 leaving
Mechanism is concerted or stepwise dependent on substrate and reaction conditions
When is the wolff-rearrangment stepwise or concerted?
Thermal - concerted
Photochemical - stepwise via carbenes
How do ketens react with NuH or A=B group?
What is the orbital requirement for migration in the Wolff rearrangment?
Bond whihc migrates must be antiperiplanar to the C-N+ bond which is broken
What is the Doering-LaFlamme allene synthesis?
Alkene to allene
Steps: CHBr3 & NaOH, then BuLi
What is the Skattebol rearrangmenet?
Geminal dihalo cyclopropane to an allene using an organolithium base
Via a C-H insertion
What are the types of carbene addition reactions?
Stereospecific for singlet carbenes - concerted reaction
Non-stereospecific for triplet carbenes - radical reaction
Distinguishes between them
Why do triplet carbenes have non-stereospecific reactions?
Spin inversion (requiring molecular collision) may be slower than bond rotation leading to stereochem scrambling
Bond rotation causes triplet to singlet state
What is the Reimer-Tiemann reaction?
Formylation of phenol to give ortho as major product with meta as minor
Uses CHCl3 and NaOH
Base deportonates CHCl3 which alpha-eliminates to give dichlorocarbene which is attacked by aromatic ring
How can carbenes add to benzene?
Very electrophilic carbenes - requires strong EWG like an ester
Heat in benzene and causes 6π electrocyclic ring opening
What is the simmons smith reaction?
Alkene + CH2I2 with Zn to form a stereospecific cyclopropane
Goes via a zinc carbenoid (IZnCH2I) which can be coordinated by a OH group (adds to same side)
How are alpha-diazo ketones made?
From carboxylic acids: Arndt-Eistert homogylation
From acid anhydride: K2CO3 and TsN3
What is the Arndt-Eistert reaction?
Homologated carboxylic acids or their derivatives
By reaction of acyl chloride with diazomethane
XS diazomethane can be destroyed by addition of small amounts of acetic acid or vigorous stirring
Then can do the Wolff-Rearrangement
How do carbenes react with nucleophiles?
Nucleophiles attack carbene and -ve charge then attacks an electrophile
How are nucleophillic carbenes used for the benzoin reaction?
Acts like a good nucleophile in resonance form, stabilises adjacent -ve charge, good LG
What is the benzoin reaction?
Coupling between two aldehydes to allow preparation of alpha-hydroxyketones
Uses N-heterocyclic carbene salt and base
What is a nitrene?
R-N
Neutral monovalent N species with 6e- around it
Isoelectronic with carbenes, but more reactive as more electrophillic
What is the structure of nitrenes?
Linear although they do have triplet and singlet states
Larger energy separation between states - triplet is usually ground states (unless very good π donor substitutent)
How are nitrenes formed?
Thermolysis or photolysis of azides
Reduction of nitro compounds using PR3
Carbazole synthesis using pschorr reaction
Generation from isocyanates using hv
What is the Pschorr reaction?
Preparation of biaryl tricyclics by intramolecular substitution of one arene by an aryl radical
Radical is generated in situ from an aryl diazonium salt by copper catalysis
How do nitrenes add to alkenes?
High conc of olefin causes singlet to react stereospecifically and low olefin conc there is a ground state to a triplet then will react non-stereospecifically
Competing reaction is 1,3-dipolar cycloaddition to form triazoline which breaks down under heat/hv to aziridine
What conditions do nitrenoids require for C-H insertion?
Better yields when milder conditions
Uses oxidant PhI(OAc)2 and Rh catalyst
What occurs when alkyl azides are photolysed?
Imines are formed via a concerted 1,2-shift
Nitrenes are most likely not the intermediate
What is the Curtis rearrangment?
Thermal decomposition of carboxylic azides to produce and isocyantes
Retention of config in migrating group
Isocynates + R’OH → RNHCOOR’
Isocynates + H2O → RNH2 + CO2
Isocynates + R’NH2 → RNHCONHR’
What is the structure of isocyantes?
What is the mechanism of the curtis rearrangment?
What is the Hoffman rearrangment?
Amide → Amine
RCONH2 → RNHCOOH
Reagents: Br2 & NaOH
What is the lossen rearrangement?
hydroxamate ester → isocyanate → amine
Reagents: NaOH to iso, then water to amine
Deprotonates amine group and causes rearrangement
What is the schmidt reaction?
Carbonyl + HN3→ amine/amide
Via isocyanate intermediate
Alt: use an alkene to form an imine
What are the different forms of the Schmidt reaction?
Carboxylic acid to amine
Ketone to amide (via azidohydrin)
Aldehydes to nitrile
Alkene to imine
Intramolecular to alkyl azides (can form rings)
What is the beckmann rearrangment?
Oxime to amide by NH insertion
Reagents: H2SO4 conc and heat then water
Which group migrates in the beckmann rearrangement?
Group anti to the LG, and retains config
Oximes can undergo E/Z isomerism in acidic cond
What is the Neber rearrangement?
Ketoxime is converted into an alpha-aminoketone
Using NaOR then water
Which substituent migrates in the neber rearrangement?
Substituent possesing most acidic H migrates
What is the Steiglitz rearrangement?
1,2-rearrangement of trityl amine derivatives to triaryl imines
Reagent is PCl5 or AgNO3 & MeOH
What is the Baeyer-Villiger oxidation?
Conversion of a ketone to an ester by O insertion
mCPBA in DCM
Via e- deficient transition state (EWG on the O) so group stabilising the +ve charge more migrates
