(Hive Bee)
07-10-03 10:59
No 446240
      PEAs from benzenes via Friedel-Crafts reaction
(Rated as: excellent)

Tetrahedron Letters, 1980, 21, 1719-1722 (

Cyclic carbamates as reagents for alkylamination of aromatic derivatives under Friedel-Crafts conditions

Abstract: Aryl(ethyl-) and propylamines are obtained with good yields by decarboxylation-alkylation process applied on aluminium trichloride-cyclic carbamte complexes. The coupling of two aromatic units is observed in the case of oxazolidinone-toluene reaction.

The synthesis of arylalkylamines and particularly 3-arylpropylamines usually required several steps (1). We report on the use of cyclic carbamates (n = 2, 3) as being compounds that are well suited for introducing the alkylamine chain intro aromatic derivatives by a decarboxylation-alkylation process using aluminium trichloride as the activator reagent.

Previous work in this field has shown that various heterocyclic compounds such as oxazolines (2), azalactones (3), and aziridines (4) lead to reactive intermediates under Friedel Crafts conditions. Oxazolidinone A itself undergoes the same process as reported earlier, although with some uncertainty (5).

Cyclic carbamates (n = 2, 3) have been easily prepared from the corresponding aminoalcohols and ethylcarbonate under basic conditions (6, 7) and have shown good complexing properties towards Lewis acids. For example stable complexes have been isolated from reactions between carbamates A and B and BF3, TiCl4 and AlX3 in methylene chloride at room temperature. Among them aluminium trichloride-carbamate complexes have shown a good tendency to decompose when heater in aromatic solvents and lead to decarboxylated products. Usually the reaction is carried out by dissolving 4 x 10-2 mole of the carbamate in 150 ml of an aromatic solvent in an inert atmosphere and then dissolving 8 x 10-2 mole of aluminium trichloride. The mixture turns rapidly into a dark homogeneous solution under refluxing. Working up the mixture by a 30% NaOH solution then extracting the solution gives the products described below.

As shown in the table, the reaction occurs with tetrahydrooxazinone B (n = 3, R = H) in benzene, toluene or chlorobenzene with good yields, giving rise to the corresponding substituted arylpropylamines 4, 5, 6.

Amines 5 and 6 are obtained as a mixture of o- and p-isomers as has been shown by the NMR spectra of their corresponding sulfonamides, i.e. benzenesulfonamide of 5 clearly shows two sharp singlets in a 3:2 ratio at 2.12 and 2.20 ppm for the methyl  gropup.

Oxazolidinone A and C (n = 2, R = H, phenyl) lead respectively to phenethylamine (65%) and N-phenyl-phenethylamine 3 (20%) depending on the aromatic solvents used.

The reactivity of carbamates A, B, C has been found to be sensitive to the concentration of aluminium trichloride.

The decarboxylation process with either A or B is in fact completely  inhibited if fewer than two equivalents of the Lewis acid are used. Interestingly, N-phenyl oxazolidinone C leads to 2-chloroethylphenylamine 8 if 1,5 equivalents of aluminium trichloride are used.

Such a result suggests a general path for the decarboxylation process which involves first the incorporation of a chlorine atom coming from the AlX3-carbamate complex followed by a classic Friedel-Crafts alkylation of the aromatic nucleus.

Another fact worth being noticed is the coupling of two aromatic units which occurs in the case of compound A. Traces of diphenylethane (9) have been detected as a side product during the synthesis of phenethylamine 1, while 1,2-ditolylethanes (2) are formed exclusively in toluene.

This difference in reactivity between A and B is probably related to the formation of a more strained intramolecular complex of type D which in turn favours the C-N bond's breaking in the case of compound A (8).

The reaction probably occurs at the amidation stage D since no incorporation of toluene is obtained if the same reaction is applied to the corresponding phenethylamine-AlCl3 complex prepared independently.

Compounds Solvent Productsa, c, d
Yield bp/torr
Lit. bp/torr
1H NMR (CDCl3)
Oxalidinone, n = 2, (A) Benzene + 5% of (9)
pNH (116)
65b 81/14
too lazy wink
Oxalidinone, n = 2, (A) Toluene 2 74 90-101/0.5  
Oxalidinone, n = 2, (A) Chlorobenzene 3
o, p. isomers
21 60/0.2  
Tetrahydro-oxazinone, n = 3, (B) Benzene 4
80 98/14
Tetrahydro-oxazinone, n = 3, (B) Toluene 5
o, p. isomers
BSA (oil)
77 62/0.1  
Tetrahydro-oxazinone, n = 3, (B) Chlorobenzene 6
o, p. isomers
BSA (oil)
55 66/0.2  
N-phenyl-oxazolidinone n = 2, R = phenyl, (C) Benzene 7
BSA (80)
60 125/0.1  
N-phenyl-oxazolidinone n = 2, R = phenyl, (C) Benzene 8
pNB (86)
48 57/0.05  

(a) 3, 5 and 6 are mixtures of o, p. isomers - the ratio has been determined only in the cases of 5 as a 3/2 o/p derivative in the light of the NMR spectra of theri benzenesulfonamides.
(b) traces of diphenylethane (~ 5%) were detected by VPC analysis.
(c) pNB: p.nitrobenzamide - BSA: benzenesulfonamide
(d) all derivatives and products gave correct elemental analysis C, H, N, Cl and mass spectra data.

Molecule: A ("N1C(OCC1)=O")


Molecule: B ("N1CCCOC1=O")


Molecule: C ("N1(C(OCC1)=O)c2ccccc2")


1: X = H; n = 2; R = H
3: X = Cl; n = 2; R = H
4: X = H; n = 3; R = H
5: X = CH3; n = 3; R = H
6: X = Cl; n = 3; R = H
7: X = H; n = 2; R = phenyl


(1) 3-Phenylpropylamines have been synthesized in various ways including the reductive amination of cinnamaldehyde (cf. F. Fusco and L. Canonica, Chimica e Industria, 32, 209, 1950; I. Jirkowsky and M. Rotina, Collect. Czech. Chem. Commun., 32, 1197, 1967), reduction of hydroxamic acid (cf. F. Winternitz and C. Wlotzka, Bull. Soc. Chim. Fr., 509, 1960, reudction of 3-phenylpropionitrile (cf. P. Mastagli and M. Metayer, Bull. Soc. Chim. Fr., 1091, 1948), etc., but not by the direct incorporation of the propylamine chain.
(2) A. Forestière and B. Sillion, C.R. Acad. Sc. Paris, 284 (C), 897, 1977.
(3) E. Chiorenesku, L. Bukhen-Bryledryanu and R. Shternberg, Izv. Akad. Nauk SSSR otd. Khim, 144, 1961 and 149, 1961.
(4) G.I. Braz, Dokl. Akad. Nauk SSSR, 87, 589, 1952 and 87, 747, 1952 - C.A., 48, 113, 1954.
(5) E. Aufderhaar Patent DE1292658, 1969; C.A., 71, 496516c, 1969
 It is claimed that phenethylamines have been obtained with various Lewis acids, including FeCl3, ZnCl2, BF3, but we have observed the reaction only in the case of aluminium trichloride-carbamate derivatives. Moreover toluene and oxazolidinone A react in our hands and give rise to ditolylethane but not tolylethylamine as claimed in this patent.
(6) M.E. Dyen and D. Swern, Chem. Rev., 197 t 2, 1967
(7) B.L. Philipps and P.A. Argabricht, J. Heterocyclic Chem., 3, 84, 1966
(8) E.L. Eliel and N.J. Murphy, J. Am. Chem. Soc., 75, 3589, 1953

A is commercially available, ~25 g/40$

The candle that burns twice as bright burns half as long
(Hive Bee)
07-10-03 17:21
No 446287
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This could very well bee a wonderful route to our beloved variously substituted arylethylamine!laugh

Imagine the chaos in Law Enforcement agencies if this reaction work:

-with alaninolcool

-with dimethoxybenzenelaugh

-both shocked

Someone has to try this in melted dimethoxybenzene with alaninol => ONE step to 2,5 DMA from 1,4 DB!laugh

TWO steps to DOB from 1,4 DB

This means THREE steps DOB from hydroquinone!tonguesmile - End of the world as we know itwink!

cool [hope]

Thanx Lego to point us this article!