Research & Reviews: Journal of Agriculture and Allied Sciences e-ISSN: E 2347-226X

P-ISSN: 2319-9857

A Study on Organic Synthesis via Ketene

Sarita Bishnoi*

Department of Organic Chemistry, Government Women College, Bawani

khera, Haryana, India

Short Communication

Received: 15-Apr-2022,
ABSTRACT
Manuscript No. JAAS-22-60958;
Editor assigned: 18- Apr-2022, Ketene is a colourless toxic gas with a s harp penetrating odour. It is most

Pre QC No. JAAS-22-60958 (PQ); important member of the class being Ketene itself, which is used to make

Reviewed: 03-May-2022, QC No. other important chemicals such as aspirin, acetate, acetic anhydride and

JAAS-22-60958; Revised: 17- other industrial organic compounds. It is soluble in essentially all organic

Jun-2022, Manuscript No. JAAS- solvents. This knowledge will help to the people who are interested to work in

22-60958 (R); Published: 24- manufacturing of industrial organic compounds. Ketene chemistry remains a

Jun-2022, DOI: 10.4172/2347- very active area of research worldwide.

226X.11.4.006

*
For Correspondence: Sarita
Bishnoi, Department of Organic
Chemistry, Government Women
College, Bawani khera, Haryana,
India, Tel: 9729083771;
Email: bishnoisarita04@gmail.com

Keywords: Acetylatingagent;
Ethane; Ketene; Ketene chemistry;
Organic synthesis

INTRODUCTION

A ketene is an organic compound of the form:

R1
C C O
R2
The first ketene to be prepared and characterized was diphenyl ketene. It was made by Hermann Staudinger in 1905.
Research & Reviews: Journal of Agriculture and Allied Sciences e-ISSN: E 2347-226X
P-ISSN: 2319-9857

Ketenes are highly unstable and cannot be stored. The utility of ketenes in both laboratory and industrial practice was
quickly recognized, and these species have been extensively utilized, including as intermediates in the manufacture of
acetic acid and acetic anhydride and pharmaceutical intermediates [1-5]. Ketenes are highly electrophilic at the curious Sp
carbon atom. Ketenes are characterized by presence of grouping as
If R1=R2=H, then the simplest member of ketene series is ketene.
If R1=R and R2=H, then it is known as Aldoketene.
If R1=R and R2=R’ then it is known as Ketoketene.
There are various types of ketenes depending upon R1 and R2 may be alkyl, aryl, alkenyl, alkynyl, acyl, imidoyl etc.
Ketenes in organic synthesis: Ketene is a colourless, poisonous, pungent, gas. Boiling point -410 C which oxidizes in air to
the unstable peroxide, the structure of which may be shown as

O O
Ketenes are unstable and can’t be stored. So ketenes react with nucleophile if present and in the absence of nucleophile
they dimerise.
Ketene itself gives an ester [6,7].

H2C C O O
O
enol ester(a)
Disubstituted ketenes give cyclobutadiones.

C C O O O

(b)
Monosubstituted ketenes may give either of the products (a) or (b)
Reaction with nucleophile: Ketene react with nucleophiles give acyl derivatives via. enolate.

O O
C C O C C CH C
Nu Nu
Nu

Acetylation by ketenes: Ketenes acetylates most of the compounds with an active H-atom. The much of acetylation by
ketenes can be generalized in terms of the addition of a nucleophile as the rate determining step.

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fast slow O H
H2C C O + H Z Z + H2C C OH H2C C
Z

fast

H3C C O
Z

It reacts with water and acetic acid is formed as shown

O
H2C C O + H2O H3C C OH

H2C C O + H O H H2C C OH + OH

O H
H2C C
O H

H3C C OH
O

When ketene is passed into glacial acetic acid, acetic anhydride is formed:

O O
H2C C O + H3C C OH H3C C
O
CH3 C
O

Mechanism:

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Research & Reviews: Journal of Agriculture and Allied Sciences e-ISSN: E 2347-226X
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O H
O O H2C C
CH2 C O + H O C CH3 CH3 CO H2C C OH O
H3C C
O

O
H3C C
O
H3C C
O

Ketene reacts with aliphatic or aromatic hydroxyl compound.

For e.g: It reacts with alcohol to form ester
O
H2C C O + ROH H3C C OR
It also acetylates the enolisable compounds
O O H2C C O O O
H3C CCH2 C OC2H5 H3C C CH C OC2H5 + H2C C CH2 C OC2H5
H2SO4 OCOCH3 OCOCH3

Ketene reacts with ammonia to form acetomide, and with primary or secondary to form N-alkyl acetamides:
O
NH3
H2C C O H3C S NH2

O
RNH2
H2C C O H3C CNHR
Primary amino group are acetylated extremely readily and hence it is possible to acetylate this group selectively in
compound containing both an amino group and hydroxyl group.
For example: p-aminophenol:
O
HO NH2 + H2C C O HO NH C CH3

A particularly useful reaction of this type is the acetylation of amino acids.

H
R C COOH + H
H2C C O R C COOH
NH2
NHCOCH3
Thiols are acetylated as shown below:
O
RSH + H2C C O RS C CH3
Ketenes react with halogen acid to form the acetyl halide:
O
H2C C O + HX H3C C X

Ketenes react with alkyl halide to form acid chloride:

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Research & Reviews: Journal of Agriculture and Allied Sciences e-ISSN: E 2347-226X
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O
R X + H2C C O RH2C C X

Ketene reacts with Grignard reagent to form methyl ketones

RMgX + H2C C O R C CH3
O
In addition to behaving as an acetylating reagent, ketene behaves as unsaturated compounds.
 Ketenes add on bromine to form bromoacetyl bromide.

O
H2C C O + Br2 BrH2C C Br

DESCRIPTION
Photolysis of ketenes: Ketene undergoes photochemical decomposition resulting into the formation of methylene

(carbene). Photolysis of higher ketene MeHC C O and Me2C C O formed the corresponding carbene, and in the
H2C CH2 MeHC CH2
gas phase and , respectively are the major product.

Photolysis of Me2C C O in cyclohexane solution also gave Me2C CMe2 which was proposed to form via the
cyclopropanone, which was observed by IR at 1840 cm-1.
O
H3C hv H3C
C C O H3C CH3 H3C CH3
H3C C C C
cyclohexane H3C H3C CH3
H3C CH3 -CO
H3C hv H3C hv
C C O C
H3C H3CHC CH2
H3C
Propene
Photolysis of diphenylketene in several solvents gave product derived from diphenyl carbene, but in THF the diphenyl
acetyl derivative was formed. This was proposed to form by Hydrogen abstraction by photo excited ketene forming a
radical pair that recombined.

Ph hv *
C C O Ph THF Ph
Ph C C O CH C O O
Ph Ph

Ph2HC
O
O
Formation of alkenes: Photolysis of cyclopropylideneketene gives carbene, which result in to the formation of alkene.

hv
C O C + CO H2C C CH2

Thermolysis of ketenes: Staudinger and Endle observed in 1913 that diphenylketene undergo thermolysis with loss of CO

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Research & Reviews: Journal of Agriculture and Allied Sciences e-ISSN: E 2347-226X
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and formation of diphenyl carbene, which cyclized to fluorene.

600-700
C C O C
-CO

It was also found that dimethylketene on pyrolysis gave dimethyl carbene, which formed propene and
tetramethylethylene.
H3C 8000C H3C H3C CH3
C C O C C C
H3C -CO H3C + H2C CHCH3
H3C CH3
Thermal decarbonylation of ketene is a reversible process.
Formation of cyclopentenone: The beta ketoester lost MeOH at 560C, forming the acylketene, which reacted by cyclization
and ketene loss, leading to cyclopentenone. The acylketene can also undergo decarbonylation to give cyclopentenone
derivative.
O O
O O O
C C O
OMe 5600C
O H
+ C C O
H

-CO

O O
CH

Cyclopentenone
derivative
Formation of acetophenone: Pyrolysis of diazoester gives the ketene, which undergo decarbonylation to form
acetophenone as the most abundant product.

Ph 350-4500C Ph Ph
C N2 Ph
MeO C C C C O C
-N2 MeO C MeO C
O MeO
O O

Ph
C O
Me
Formation of acetoacetic ester: Ketene on pasing on acetone cooled in solid CO2 to form diketone which is a pungent-
smelling liquid. When strongly heating diketene is depolymerised to ketene.Diketenes reacts with alcohols to form esters
of acetoacetic acid, this reaction is now being used to prepare acetoacetic ester industrially. For eg. Ethylacetoacetate is

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also prepared industrially by polymerising ketene in acetone solution to diketene, which is then treated with ethanol.A
possible mechanism is:

H2C C O
H2C C O H2C C O
H2C C O
H2C C O
H2C C O EtOH O
Et H

O H O O H O Et
H2C C CH2 C OEt H2C C C C O
H H

O O
H3C C CH2 C OEt
Formation of N-substituted acetomide: Diketene also react with primary amines to form N-substituted acetomide. For eg.
O O
H2C C O
+ C6H5NH2 H3C C CH2 C NHC6H5
H2C C O
Mechanism:
H2C C O H2C C O
+ C6H5NH2
H2C C O H2C C O O H NHC6H5
N H2C C CH2 C O
H H
C6H5

O O O H NC6H5
H3C C CH2 C NHC6H5 H2C C CH2 C O

Formation of alkenes: Diphenyl ketene was found to react with the phosphorous ylide to form tetraphenylallene by
Luscher. This reaction was later developed by Wittig and Haeg.
Ph
C C O + Ph3C CPh2 Ph Ph
Ph C C C
Ph Ph
Cycloaddition reaction of ketenes: Cycloaddition reaction have been a characteristic feature of ketene chemistry from the
very beginning, with the isolation of the ketene dimer by Chick and Wilsmore.Staudinger found that ketene reacted with
cyclopentadiene to form addition compound that was later shown to result from net [2+2] cycloaddition, and that i
reacted eith imines to form beta-lactam and with aldehyde to form beta-lactone.Since that time, cycloaddition has

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remained the most distinctive, useful and intellectually challenging aspect of ketene chemistry.Ketene itself gives ester:-
O O
H
C C O +
H O
H2C OH
enol ester 4-5%
88-90%
Mechanism:
Cycloaddition of ketene with carbonyl group.

H H2C
C C O O
H
H O
C C O
H
Dimethyl ketene gives cyclobutadiones:

H3C O
C C O H3C CH3
H3C
CH3 H3C CH3
O C C O
CH3
Thus ketenes have a unique propensity for giving facile [2+2] cycloaddition reactions, even when other pathways are
available.
This feature of ketene chemistry is of major importance for preparative purposes in that the reaction with diene and
alkene gives cyclobutanone.
Formation of cyclobutanone:
O
O
C
C
H

Ph
C C O O
Ph
Ph
Ph
Formation of enol:
H3C
C C O H3C O H3C O
H H
CH3
O C C
H O HO CH3
Formation of enone:

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O H
O
C C C C
C C Ph C
Ph Ph R Ph
[2+2] cycloaddition of ketenes with alkenes:
t-Bu O
CH3
t-Bu H3C NC
C C O + C C C
NC H3C CH3

Formation of beta-lactams: Cycloaddition of ketenes with imines: The reaction of ketene with imines forming beta-lactams
is the most straight forward method for the synthesis of these compounds, which have valuable application in the
synthesis of antibiotics.

R1 H R2 H H H
C 0 C R1 R2
C
+ N N
C CH2Cl2
R3 O R3
O
lactam
Mechanism:
2
R1 H R2 H R1 HR H H H
C C C C R1
Ring Closure R2
C N C N N
R3 O R3 O R3
O
cis-(lactam
Isomerise R1 Strong electron
donating group

R1 HH R2
C C
C N
O R3

Ring Closure

H R2
R1
H
N
O R3

Translactam
1
R = Weak eiectron donating
group and eiectron withdrawing effect
The stereoselectivity is generated as a result of the competition between the direct ring closure and the isomerisation of
imine moiety in the zwitterionic intermediate. The ring closure step is the most likely an intramolecular nucleophilic

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addition of enolate to the imine moiety, which is obviously affected by the electronic effect of the ketene and imine
substituent. Electron donating ketene substituents and electron withdrawing imine substituents accelerate the direct ring
closure leading to a preference for cis beta-lactam formation. While electron withdrawing ketene substituents and
electron donating imine substituents slow the direct ring closure, leading to a preference for trans beta-lactam formation.
Examples:
Ph Ph Ph O
C C O + N Ph
HS Ph N
Ph
Ph
NAr Cl
Cl O
C C O + O O O
H
N
O Ar
Formation of heterocyclic compounds: Heterocyclic compound, an interimediate in a cytochalasen synthesis can be
made from acid phenyl alanine and ketene dimer in the presence of ethanol.
COOH O O
1. EtOH,H COOEt
Ph MeO
Ph C
NH2 MeOH Ph
2. HN
O O HN
Phenylalanine
O O
O
Mechanism:

O O H O H
C OH C O Et
Ph Ph OHEt Ph OH
NH2 NH2 NH2

EtOH -H2O
O
OEt O
Ph O
OEt
HN Ph OEt +O O
HN Ph O
O O NH2
O O H

NaOH

O O
C
Ph
HN
O
Formation of lactones: Generally lactones are made by Baeyer-villiger rearrangement. Lactones can also be prepared
from ketene. Let us consider lactone which is an important intermediate in the synthesis of Prostaglandins. In actual
practice, dichloroketene is much easier to make and handle then ketene itself.

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Synthesis:
O Zn O O O
CHCl2COCl RCOOOH
Et3N Cl ROH
Cl B.V. Rexn

Mechanism:

Cl H O Et3N Cl O
Cl
C C Cl C C C C O
Cl Cl Cl
Cl dichloroketene

cyclopentadiene

2+2 cycloaddition

O O Zn O
R C O OH +
ROH Cl
Cl

O O H
O
OOCOR O O C R

O O

Formation of cyclopropyl aldehyde: Cyclopropyl aldehyde can be from cyclic ketones via. ketene formation.

Cl
O O Cl
O
PPh3 CH2 OH
Cl Cl NaBH4
wittig rexn
Et3N Reduction
cyclohexanone

NaOH

CHO

cyclopropylaldehyde

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Mechanism:
O Cl
C O Cl
Cl C Cl 2+2 OH
Cl C O NaBH4 C
H
H
CH2
Et3N

NaOH

Cl
CHO
O

Synthesis of Z-Jasmone from cyclopentadiene: Jasmine flowers contain Z-Jasmine which is responsible for jasmine
fragrance and used in perfumery.
CH3

O C2H5

Z-Jasmone
Synthesis:
 Dichloro ketene (formed in situ by reaction of dichloroacetyl chloride with tri-ethylamine) reacts with cycloalkene
by [2+2] cycloaddition.
 Reductive dehalogenation with zinc in the presence of acetic acid.
 Baeyer-villiger oxidation to give a lactone.
 Reduction of the lactone to hemiacetal.
 A wittig reaction on hemiacetal affords a gama-hydroxy alkene.
 Oxidation of the alcohol to an unsaturated ketone and conversion to more stable conjugated isomer.
 Reaction with methyl lithium to yield a tert.alcohol.
 Oxidation under acidic condition is attended with allylic rearrangement to give jasmone.

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CHCl2COCl Zn
O O H2O2
Et3N O
CH3COOH
CH3COOH
Cl O
Cl
Lactone

DIBAL-H

O O OH
Ph3PC3H7BrH
O

C2H5 Jone's reagent NaH, DMSO OH

C2H5
Hemiacetal
NaOH
H2O

O OH CrO3, H2SO4
CH3Li CH3
CH3 H2O
C2H5
C2H5 O C2H5

Z -Jasmone

CONCLUSION

A variety of hydroxylic compounds can add as nucleophiles, forming either enol or ester products. As examples, a water
molecule easily adds to ketene to give 1,1-dihydroxyethene and acetic anhydride is produced by the reaction of acetic
acid with ketene. Reactions between diols (HO−R−OH) and bis-ketenes (O=C=CH−R′−CH=C=O) yield polyesters with a
repeat unit of (−O−R−O−CO−R′−CO).
Ethyl acetoacetate, an important starting material in organic synthesis, can be prepared using a diketene in reaction with
ethanol. They directly form ethyl acetoacetate, and the yield is high when carried out under controlled circumstances; this
method is therefore used industrially. This knowledge will help to the people who are interested to work in manufacturing
of industrial organic compounds.

REFERENCES

1. Kolb M, et al. Ketene dithioacetals in organic synthesis: recent developments. Synthesis. 1990;171-190.
2. Huang L, et al. Ketene dithioacetals in organic synthesis. Tetrahedron Letters. 2020;61:151363.
3. Tidwell TT (2006) Ketenes. (2nd edition). John Wiley & Sons, Hoboken, New Jersey.
4. Zhu PC, et al. Preparation of monoacetylated diols via cyclic ketene acetals. J Org Chem. 1995;60:5729-5731.
5. Pemberton N, et al. Synthesis of multi ring-fused 2-pyridones via an acyl-ketene imine cyclocondensation. Org
Lett. 2006;8:935-938.
6. Huang J, et al. One-pot synthesis of substituted isothiazol-3 (2H)-ones: Intramolecular annulation of α-carbamoyl
ketene-S, S-acetals via PIFA-mediated NS bond formation. Synthesis. 2007;2791-2796.
7. Pan L, et al. Recent developments of ketene dithioacetal chemistry. Chem Soc Rev. 2013;42:1251-1286.

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