GB2220000A - Preparation of iodoalkynyl carbamates - Google Patents

Description

TROY 70/3293/01 PREPARATION OF IODOALKYNYL CARBAMATES This invention

relates to a process for the preparation of iodoalkynyl carbamates which have utility as fungicides and algaecides.

There are various nbwn processes for preparing iodoalkynyl carbamates of formula I [IC-:C-(CH 2)n-O-CONH-1 m R in which R is an alkyl, aryl or alkaryl group having up to 20 carbon atoms, and m and n are each independently 1, 2 or 3. For example, US-A- 3923879 discloses the following two-step synthesis:

HC:-::C-(CH 2) n-OH + NaOI -)- IC=-C-(CH 2) n -CH + NaOH 2) IC=-C-(CH 2) n -OH + R(NCO) m [IC=-C-(CH 2)n-O-CONH-1 m R Therefore, in order to prepare the current commercial product, i.e. iodopropargyl buty.1 carbamate, a 20 starting material is propargyl alcohol, and the reactants ') are iodopropargy! alcohol and butyl in step ( isocyanate.

lodopropargyl alcohol is a severe skin and eye irritant, and consequently presents problems in handling.

It is also subject to explosive decomposition above 63C. Further, its isolation involves extractions with diethyl ether which has a very low flash-point (-451C) and which is hazardous to handle. Impurities in the iodopropargyl alcohol cannot be easily removed and are thus generally present in the final product, causing undesirable and -1 objectionable odours.

Butyl isocyanate is a highly toxic material and also a strong skin and eye irritant.

EP-A-0014032 describes another method for preparing compounds of formula I, comprising reacting an alkynol of the -formula HCEC-(CH OH with an isocyanate of the 2)n 1-ormula R(NCO) to give a carbamate of the formula L m [HC=-C-(C11 2)n -0-CONHI m R. This is then reacted with NaOI. lk" Although this method avoids the preparation of iodopropargyl alcohol as an intermediate, it includes the use of isocyanates which are known to be extremely toxic and irritant.

- According to the present invention, a method for the preparation of a compound of formula I comprises the steps of reacting an alkynol chloroformate of the formula CH=-C-(CH 2)n-O- COC1 with an amine of the formula R(NH 2)m and reacting the resultant carbamate of the formula [CH=-C-(CH,)n -0-CONH-] m R with an iodinating agent. Preferably, m and n are each 1.

is Alkynol chloroformates which may be used in the novel method include chloroformates of 2.-propyn-l-ol (propargyl alcohol), 3-butyn-l-ol and 3-butyn-2-ol. Amines which may be used in the method include methylamine, propylamine, butylamine, hexyl.amine, 2 octadecylamine, hexane-1,6-diamine, ethylenediamine, aniline, 4- chloroaniline, 4-chloro-1,3-phenylenediamine, 2"-chlorophenyl)ethylamine, cyclohexylamine and -( 2,4-diaminotoluene.

Additional substituents may be present in the given amines. Examples are halogens such as Cl, Br and F, and c 1-10 alkyl.

The amine reactant may include substituents on R which make very difficult, if not impossible, the formation of carbamates of alkvnols by their presence in the isocyanates used in the known syntheses. Typical of such substituents are carboxyl and hydroxyl groups. h, Therefore,'amines that can be used also include anthranilic acid, hydroxyanthanilic acid, aminophenylacitic acid, aminophenol, aminobenzoic acid, 35 ethanolamine, propanolamine, hydroalkanolamines, and amino-acids such as glycine and aminobutyric acid.

This list is not intended to be all-inclusive or to exclude other compounds containing amino groups, such as cyclic or heterocyclic compounds, or combinations of amino groups with any other substituents such as nitro, cyano, amido and sulphur, as are well-known in chemical technology.

The first step of'the novel method comprises reaction of the alkynol chloroformate with the amine. It can be carried out by various methods which are known to the art of chemicall synthesis. The amine is preferably added to the alkynol chlordformate at a controlled rate, so that the reaction temperature does not rise undesirably. External cooling may be applied if and as required.

The reaction is carried out in the absence of a solvent, or using a solvent that is inert with respect to the chloroformate and amine groups. The physical 0 characteristics of the end product may indicate whether or not solvents are required and, if so, the preferred type of solvent. Suitable solvents which may be used include benzene, toluene, xylene, methylene chloride, trich1crethylene and dimethyl'Lormamide.

There may also be used as a component of the reaction an acid acceptor such as sodium bicarbonate, sodium carbonate, calcium carbonate, pyridine, triethylamine and/or sodium hydroxide. These compounds enable the reaction to proceed more rapidly or more completely, by removing the HC1 formed, and minimising possible side- reactions which may occur.

The selection of the acid acceptor depends upon a number of factors such as the nature of the amine, the physical characteristics of the end product, and the ease of handling in actual production.

The second stage of the novel method involves the iodination of the carbamate formed-in the first step. Iodination of the carbamate can be carried out in aqueous medium, using an iodinating agent such as a combination of sodium hypochlorite, an alkali metal hydroxide and iodine. Alternatively, sodium hypochlorite and sodium iodide may be used.

The reaction is facilitated by, but not necessarily carried out in, the presence of a water-miscible solvent in which the dissolved alkynol carbamate can react with the iodinating agent in essentially a single phase.

The iodination may also be accomplished and facilitated by using a suitable surfactant to disperse the carbamate in water in which it reacts with the is iodinating agent. The surfactants may be used together with protective colloidg and compounds such as are generally known in the art for preparing stable fine emulsions or dispersions. For instance, sorbitol esters or polyacrylates may be used. 20 The following Examples illustrate the invention. Example 1(a) Propargyl butyl carbamate 100 g water were charged into a 500 mI flask, and 30 a sodium carbonate monohydrate were added. The solution was agitated, and 30 g monobutyl amine added. The mixture was cooled to OIC and agitated rapidly while slowly adding, simultaneously, 48.2 g (0.4M) propargyl chloroformate and 100 mI, sodium hydroxide solution (M. The reaction temperature was maintained at OOC. After the chloroformate and the alcohol additions were completed, agitation was continued for five minutes. Agitation was then stopped, and the salts were allowed to settle out. The reaction mixture separated into two layers; the lower aqueous layer was drawn off and discarded. The upper layer comprised propargyl butyl carbamate, obtained in about 95% yield.

Example 1(b) Iodopropargyl but-yl carbamate 24.5 g propargyl butv! carbamate (as prepared in Example la) were dissolved in 110 g methanol. The solution was agitated and maintained at OOC. A total of 20 g powdered iodine was then added. After the total iodine was dissolved and/or dispersed, 50 9 sodium hypochlorite solution (11.3% NaOC1) was then added. A precipitate of iodopropargyl butyl carbamate was formed as a slurry. This slurry was poured into 500 ml cold water, and the resulting precipitate was filtered and washed. An 85% yield of a pale yellow-to-white powder was obtained. Example 2(a) Propargyl hexyl carbamate 30.3 g (0.3M) hexylamine were dissolved in 710.g toluene. The solution, contained in a 3-neck flask equipped with an agitator, reflux condenser, thermometer and addition funnel, wa:s agitated as 35 g sodium carbonate (anhydrous) were added. The mixture was heated to 601C while slowly adding 36 g propargyl 1 chloroformate.

The reaction mixture was agitated and maintained at 601C for two hours. It was then filtered, and the toluene stripped off under vacuum.

Propargyl hexyl carbamate, as a pale-amber oily liquid, was obtained in 80% yield.

Example 2(b)

The product obtained from Example 2(a) described above was iodinated in the same manner as in Example 1(b). The end product, obtained in 78% yield, was a pasty solid that melted at 300C.

Example 3 Propargyl phenyl carbamate 9.31 (0.1M) g aniline were dissolved in 75 g toluene. The solution was agitated, and 11.6 g Na 2 CO 3 were added. To the rapidly agitated mixture, 12 g (0.1M) propargyl chloroformate were added slowly. A yellow precipitate formed. The reaction mixture was maintained at 600C for 2 hours. The product was filtered and washed with toluene, JEollowed by water. 15 g (92% yield) propargyl phenyl carbamate was obtained as a pale-yellow powder.

Example 4(a) Propargyl p-chlorophenyl carbamate 12.7 g (0.1M) p-chloraniline were dissolved in 85 g toluene. The solution was agitated, while adding 12 g sodium carbonate (anhydrous powder).

To this solution were added 12 g propargyl chloroformate. The reaction mixture was maintained at 600C for 2 hr, with agitation. A yellow-green precipitate was produced.

This precipitate was filtered and wAshed with toluene, followed by washing with water. -The residue was dried to yield a yellow powder. 16.5 g (83% of the theoretical yield) of propargyl p-chlorophenyl carbamate was obtained. Example 4(b) Iodopropargyl pchlorophenyl carbamate This reaction was carried out by the same procedure as described in Example 1(b) above:

9.9 g propargyl p-chlorophenyl carbamate were dissolved in 100 g methanol. The solution was agitated and the temperature reduced to OIC. 0.1 g sodium hydroxide was added, followed by 6.35 g iodine crystals and 17 g of an 11.3% sodium hypochlorite solution. A precipitate formed, which was filtered and washed thoroughly with water. Iodopropargyl p- chlorophenyl carbamate was obtained as a light tan powder.

Claims (9)

1. A method for the preparation of a ccrrpound ha.;-'Lng the formula [IC7-C-(CH 2)n -0-CONH] m R in which R is an alkyl, aryl or alkaryl group having up to 20 carbon atoms, and m and n are e ach independently 1,

2 or 3, which comprises the steps of reacting an alkynol chloroformate of the formula CH---:C-(CH,)n- O-COC1 with an amine of the formula R(NH 2)m, and reacting the resultant carbamate of the formula [CHE-C-(CH 2)n -0-CONH-] m R with an iodinating agent. 2. A method according to claim 1, in which m and n are each 1.

3. A method according to claim 2, in which the amine is butylamine.

4. A method according to claim 21, in which the amine is hexylamine.

5. A method according to claim 2, in which the airine is aniline.

6. A method according to claim in whic 1 h the amine is p-chloroaniline.

7. A method according to any preceding claim, in which the iodinating agent is iodine.

8. A method according to any of claims 1 to 6, in which the iodinating agent is an iodide.

9. A method according to claim 1, substantially as exemplified herein.

Published IG89 at The PatentOffice, State House, 6671 High Holborn, LondonWC111,4TP. FurtAlercDpies maybe obtainedfrom The Patent OfE=Sales Branch, St Mary Cray, Orpington, Kent BR-5 3RD. Printed by Multiplex technique; ltd, St Mary Cray, Kent, Con. 1/87