N-Methylanilinium Trifluoroacetate

Ph+NH2Me CF3CO2-

[29885-95-8]  · C9H10F3NO2  · N-Methylanilinium Trifluoroacetate  · (MW 221.20)

(a-methylenating agent for ketones;1 activates internucleotide coupling2)

Alternate Name: N-MATA.

Physical Data: mp 66.5 °C.

Solubility: insol pentane; sol THF; very sol MeCN.

Form Supplied in: crystalline white salt.

Analysis of Reagent Purity: elemental analysis.

Preparative Method: prepared from commercial grade Trifluoroacetic Acid and N-methylaniline (1:1) in dry Et2O under a nitrogen atmosphere with cooling in an ice-bath.1c

Purification: by sublimation and drying in a desiccator under vacuum at rt.

Handling, Storage, and Precautions: nonhygroscopic; not deliquescent; can be weighed in the air and stored for months under an inert atmosphere.

Methylene Transfer Reagent.

Ketones of various types form a-methylene ketones by direct methylene transfer from formaldehyde in the presence of N-MATA (eq 1).1,3,4

Both paraformaldehyde and trioxane can be used as the source of formaldehyde, but, with the latter, low yields of methylene ketones are sometimes obtained.3 With cyclohexanone, cyclopentanone, or aldehydes, preformation of the iminium intermediate [CH2=+NMePh] is recommended from paraformaldehyde and N-MATA prior to addition of the carbonyl compound.1c Saturated1 and unsaturated,1b cyclic,1a,c,3 and acyclic,1b,4 as well as methyl ketones,1b,4 can be successfully used in the process (eqs 2 and 3).1a,4

Linear methyl ketones react at both the a- and a-positions to give a mixture of regioisomeric methylene ketones (eq 4),1b as well as some divinyl ketone as a side product.

The reaction is not applicable to g- or d-lactones, or strained cyclic ketones such as norcamphor or cyclobutanone.1a,c

Activating Agent in Internucleotide Coupling.

Deoxynucleoside methyl- and phenylphosphoramidites2 and also phosphorothioamidites5 are effectively activated by N-MATA for condensation with other suitably protected nucleosides to give deoxydinucleoside phosphates (eq 5).2 Phosphorodithioates5 or oligonucleotides (over 95%) have also been prepared in this manner using a polymer silica gel support.2

In the synthesis of deoxydinucleoside phosphorodithiolates, however, N-MATA causes excessive detritylation and the most satisfactory activator in this process is pyridinium tetrafluoroborate.5

1. (a) Gras, J. L. TL 1978, 2111. (b) Gras, J. L. TL 1978, 2955. (c) Gras, J. L. OS 1981, 60, 88.
2. Fourrey, J. L.; Varenne, J. TL 1984, 25, 4511.
3. Kruizinga, W. H.; Kellogg, R. M. JACS 1981, 103, 5183.
4. Pavlychenko, A. I.; Purvaneckas, G.; Smirnova, N. I.; Titov, V. V. ZOR 1986, 22, 1524.
5. Brill, W. K. D.; Nielsen, J.; Caruthers, M. H. JACS 1991, 113, 3972.

Valerij A. Nikolaev

St. Petersburg State University, Russia

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