Novel 1-phenethylimidazoles substituted at the position .beta. to the imidazole ring by an optionally substituted hydrocarbyl carbonate or a mono-, di-, or trithiocarbonate are useful as antimicrobial agents and as intermediates in the preparation of novel 1-phenethylimidazoles substituted at the position .beta. to the imidazole with a mercapto. Both the former and latter compounds are useful as intermediates in the preparation of certain 1-[.beta.-(R-thio)phenethyl]imidazoles.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to novel 1-phenethylimidazoles substituted at the 
position .beta. to the imidazole ring by an optionally substituted 
hydrocarbyl carbonate or a mono-, di-, or trithiocarbonate, the use of 
these imidazoles as antimicrobial agents, the combination of these 
imidazoles with a suitable carrier, the preparation of these imidazoles, 
and the use of these imidazoles as intermediates in the preparation of 
1-[.beta.-(R-thio)phenethyl]imidazoles. 
This invention further relates to certain novel 1-phenethylimidazoles 
substituted at the position .beta. to the imidazole ring with a mercapto 
and the acid and base salts thereof, the preparation of these imidazoles, 
and the use of these imidazoles in the preparation of 
1-[.beta.-(R-thio)phenethyl]imidazoles as well as other 
1-phenethylimidazoles substituted at the position .beta. to the imidazole 
ring with a mono-, di- or trithiocarbonate or a thio-or dithioester. 
2. Prior Art 
It is generally known in the art that certain 1-(.beta.-aryl)ethylimidazole 
ethers and amines have anti-fungal and anti-bacterial activity. See, for 
example, U.S. Pat. Nos. 3,717,655 and 3,839,574, both to Godefroi and 
Heeres of Janssen and U.S. Pat. No. 3,658,813 to Godefroi and Schuermans 
of Janssen. Representative of the ethers is the compound miconazole 
nitrate having the formula 
##STR1## 
the active ingredient in Monistat.RTM. Cream sold by Ortho Pharmaceutical 
Co. Such compounds are derived from 1-(.beta.-hydroxyphenethyl)imidazole 
or 1-(.beta.-aminophenethyl)imidazoles which are optionally substituted on 
the phenyl ring. (See Godefroi, et al, J. Med. Chem., 12, 784-91 (1969). 
Other 1-ethylimidazoles which are known include those disclosed in U.S. 
Pat. Nos. 3,796,704 and 3,892,764 both to Metzger et al of Bayer and U.S. 
Pat. No. 3,914,427 to Kramer et al of Bayer. These, too, show anti-fungal 
activity. 
An entirely new class of 1-(.beta.-substituted phenethyl)imidazoles has now 
been discovered which shows very good anti-fungal and anti-bacterial 
activity. These are the 1-phenethylimidazoles which are substituted at the 
position .beta. to the imidazole with a carbonate or a mono-, di-, or 
trithiocarbonate. The existence of related compounds was hinted in the 
broad disclosure U.S. Pat. No. 3,796,704, but, unfortunately, no method 
was given for preparing such compounds. 
SUMMARY OF THE INVENTION 
The first aspect of the present invention relates to novel imidazole 
derivatives and more particularly to 1-phenethylimidazoles having the 
formula: 
##STR2## 
and the antimicrobial acid addition salts thereof, wherein 
R is alkyl, phenylalkenyl, substituted phenylalkenyl, cycloalkyl, 
cycloalkyl lower alkyl, phenylalkyl, substituted phenylalkyl, phenyl and 
substituted phenyl, said substituted phenyl, substituted phenylalkenyl, 
and substituted phenylalkyl containing at least one substitutent on the 
phenyl moiety selected from the group consisting of halo, lower alkyl and 
trifluoromethyl; 
R.sup.1 is phenyl optionally substituted with one or more substituents 
chosen from the group consisting of halo, lower alkyl and trifluoromethyl; 
and 
X, Y and Z are independently sulfur or oxygen. The subject compounds of 
Formula (I), above, exhibit antifungal, antiprotozoal and antibacterial 
activity against animal and human pathogens as well as antifungal activity 
against fungi of primarily agricultural importance. Thus, the subject 
compounds are found to be useful antimicrobials, having not only 
pharmaceutical but also agricultural and industrial applications. Thus, a 
further aspect of the present invention relates to methods of inhibiting 
the growth of fungi, protozoa, and bacteria by applying to a host object 
containing, or subject to attack by, fungi, protozoa or bacteria, a 
fungicidally, protozoicidally, or bactericidally effective amount of a 
compound of this invention. A still further aspect of the present 
invention relates to compositions for pharmaceutical, agricultural, and 
industrial use, which compositions comprise the subject compounds of 
Formula (I) in combination with a suitable carrier. 
Still another aspect of the present invention is the preparation of the 
compounds of Formula (I) set forth above. This will be discussed 
hereinafter more completely. 
Still another aspect of this invention relates to the use of the compounds 
of this invention in preparing 1-[.beta.-(R-thio)phenethyl]imidazoles. 
Finally, another aspect of this invention is a compound chosen from those 
represented by 
##STR3## 
wherein R.sup.1 is defined hereinbefore, especially 2,4-dichlorophenyl, 
and the acid or base salts thereof. A salt of the compound of Formula (II) 
may be prepared by reacting a compound of Formula (I) where X is S with a 
suitable base. By reacting a compound of Formula (II) with 
##STR4## 
R.sup.2 B or 
##STR5## 
wherein R, Y and Z are previously defined, A and B are suitable leaving 
groups, and R.sup.2 is defined hereinafter, the compounds of Formula (I), 
1-[.beta.-(R.sup.2 -thio)phenethyl]imidazoles, or the compounds of U.S. 
patent application Ser. No. 662,786 filed Mar. 1, 1976 may be respectively 
obtained. 
Specific representative embodiments of the compounds, compositions, uses of 
and processes for preparing compounds of this invention will be discussed 
more completely and specifically hereinafter. 
PREFERRED EMBODIMENTS 
Compounds of the Invention 
A. definitions 
The term "alkyl" as used in the specification and appended claims refers to 
a saturated, unbranched or branched acyclic hydrocarbon group containing 1 
to 12 carbon atoms inclusive, such as methyl, ethyl, n-propyl, isopropyl, 
n-butyl, i-butyl, t-butyl, n-pentyl, n-heptyl, n-octyl, n-nonyl, n-dodecyl 
and the like. The term "lower alkyl" refers to an alkyl group as 
previously defined containing 1 to 4 carbon atoms, inclusive. 
The term "cycloalkyl" as used herein refers to a saturated, monocyclic 
hydrocarbon group having 5-8 ring carbon atoms, e.g. cyclohexyl. The term 
"cycloalkyl lower alkyl" refers to a cycloalkyl group as previously 
defined attached to an unbranched acyclic hydrocarbon group containing 1 
to 4 carbon atoms, such as cyclopentylpropyl, cyclohexylmethyl, 
cyclooctylethyl, and the like. The term "phenylalkenyl" refers to a 
hydrocarbon moiety in which the alkenyl portion containing 3 to 4 carbon 
atoms is attached to a phenyl ring such as 3-phenyl-2-propenyl, 
4-phenyl-3-butenyl, and the like. The term "phenylalkyl" refers to a 
hydrocarbon moiety in which the alkyl portion contains 1 to 3 carbon 
atoms. Representative examples include benzyl, 3-phenylpropyl and the 
like. The term "halo" as used herein refers to chloro, fluoro and bromo. 
The term "antimicrobial acid addition salts" refers to salts of the 
subject compounds which possess the desired activity and which exhibit 
minimal undesirable biological or other effects. These salts are formed by 
reacting a compound represented by Formula (I) with inorganic acids such 
as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and 
phosphoric acid and the like, or organic acids such as acetic acid, 
propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, 
malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, 
citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic 
acid, ethanesulfonic acid, p-toluenesulfonic acid, and the like. 
All compounds of Formula (I) [and Formula (II)] have at least one chiral 
center, i.e., the carbon atom to which are attached the R.sup.1, H--, 
##STR6## 
[or --SH in Formula (II)] moieties. Accordingly, the compounds of the 
present invention may be prepared in either optically active form, or as a 
racemic mixture. Unless otherwise specified, the compounds described 
herein are all in the racemic form. However, the scope of the subject 
invention herein is not to be considered limited to the racemic form, but 
to encompass the individual optical isomers of the subject compounds. 
If desired, racemic intermediates or final products prepared herein may be 
resolved into their optical antipodes by conventional resolution means 
known per se, for example, by the separation (e.g. fractional 
crystallization) of the diastereomeric salts formed by reaction of, e.g. 
racemic compounds of Formula (I) or the racemic alcohol precursors of 
Formula (III), infra, with an optically active acid, or of the 
diastereomeric esters formed by reaction of the racemic compounds of 
Formula (II) or the racemic alcohol precursors of Formula (III) with an 
optically active acid. Exemplary of such optically active acids are the 
optically active forms of camphor-10-sulfonic acid, 
.alpha.-bromocamphor-.pi.-sulfonic acid, camphoric acid, menthoxyacetic 
acid, tartaric acid, malic acid, diacetyltartaric acid, 
pyrrolidone-5-carboxylic acid, and the like. The separated pure 
diastereomeric salts or esters may then be cleaved by standard means to 
afford the respective optical isomers of the compounds of Formulae (I) or 
(II) of the precursor alcohols of Formula (III). Particularly valuable is 
the resolution of an alcohol of Formula (III), e.g. by fractional 
crystallization of a salt with an optically active acid (e.g. dibenzoyl 
tartarate). The thus resolved alcohol may then be employed as discussed 
hereinafter to prepare the compounds of this invention. 
B. specific Sub-Groups of Formula (I) 
Eminently suitable as the compounds of this invention represented by 
Formula (I) are those wherein R is as follows: 
alkyl of up to 10 carbons such as methyl, ethyl, propyl, isopropyl, 
n-butyl, isobutyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, 
n-decyl and the like, alkyls of 1 to 4 carbon atoms, both branched or 
straight chain, and those of 5 to 10 straight chain carbon atoms being 
preferred; 
phenyl optionally substituted with one or more (preferably 1 or 2) 
substituents chosen from halo or lower alkyl, when only one substituent is 
present it is preferably at the 4-position, particularly 4-chloro, 
4-bromo, 4-fluoro, and when two substituents are present they are 
preferably halo at the 2,4- or 3,4 - positions chloro being the most 
particularly preferred substituent in either case; 
benzyl optionally substituted on the phenyl ring with one or more 
(preferably 1 or 2) substituents chosen from halo or lower alkyl, when 
only one substituent is present, it is preferably halo at the 4-position 
and when two substituents are present they are preferably halo at the 2,4- 
or 3,4- positions, chloro being the most particularly preferred 
substituent in either case; or 
3-phenyl-2-propenyl optionally substituted at the 4-position of the phenyl 
ring with a halo, preferably chloro. 
Eminently suitable as the compounds of Formula (I) are those wherein 
R.sup.1 is phenyl substituted with 1 to 3 substituents chosen from halo 
and lower alkyl, preferably 4-halophenyl, (particularly 4-chlorophenyl) 
2,4- or 3,4-dihalophenyl (particularly 2,4-dichlorophenyl), or 
2,4,6-trichlorophenyl. 
Especially suitable as combinations of X, Y and Z are those wherein at 
least one of the components is S, particularly the following combinations: 
##STR7## 
preferably X is S. The xanthate 
##STR8## 
is particularly preferred. 
In the case where R.sup.1 is 2,4-dichlorophenyl or 4-chlorophenyl and (a) 
where X, Y and Z are each oxygen (O), then R, if an alkyl, will preferably 
contain 4-9 carbon atoms; (b) where one of X, Y or Z is sulfur (S) and the 
other two are O, then R, if an alkyl, will preferably have 2-7 carbon 
atoms; (c) where one of X, Y or Z is O and the other 2 are S, then R, if 
alkyl, will preferably contain 1-7 carbon atoms; and (d) where all of X, Y 
and Z are S, then R, if alkyl, will preferably have 1-5 carbon atoms. 
An extremely preferred subclass of the compounds of this invention are 
those encompassed by the formula of I, above, wherein 
R.sup.1 is 2,4-dichlorophenyl; 
R is alkyl of 1-7 carbon atoms, phenyl substituted with halo, particularly 
chloro, at 1 to 2 positions, (especially 4-chloro, 3,4-dichloro or 
2,4-dichloro), benzyl substituted at the 4-position (i.e., p-substituted) 
with a halo (especially chloro) or at the 2,4- or 3,4- positions with 
chloro; 
X is S; and 
Y and Z are independently S or O. 
C. specific Sub-Groups of Formula (II) 
Particularly valuable compounds of this invention represented by Formula 
(II) are those wherein 
R.sup.1 is phenyl having 1 to 3 substituents chosen from halo and lower 
alkyl, preferably 4-halophenyl (particularly 4-chlorophenyl), 2,4- or 
3,4-dihalophenyl (particularly 2,4-dichlorophenyl), or 
2,4,6-trichlorophenyl and the acid or base addition salts thereof. 
Particularly preferred is the compound of Formula (II) wherein R.sup.1 is 
2,4-dichlorophenyl, namely 1-[2,4-dichloro-.beta.-(mercapto)phenethyl] 
imidazole and its acid or base addition salts. 
Specific examples of each of these sub-groups of part B and C, above, may 
be found in the examples contained in the specification hereinafter. 
In naming the compounds of this invention represented by Formula (I), the 
following nomenclature is used for the combinations of X, Y and Z 
(assuming R.sup.1 is 2,4-dichlorophenyl and R is ethyl): 
1. When X, Y and Z are all O, the compound is 
1-[2,4-dichloro-.beta.-(ethoxycarbonyloxy)phenethyl]imidazole; 
2. When X is S and Y and Z are O, the compound is 
1-[2,4-dichloro-.beta.-(ethoxycarbonylthio)phenethyl]imidazole; 
3. When Y is S and X and Z are O, the compound is 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonyloxy)phenethyl]imidazole; 
4. When Z is S and X and Y are O, the compound is 
1-[2,4-dichloro-.beta.-(ethylthiolcarbonyloxy)phenethyl]imidazole; 
5. When X is O and Y and Z are S, the compound is 
1-[2,4-dichloro-.beta.-(ethylthiolthiocarbonyloxy)phenethyl]imidazole. 
6. When Y is O and X and Z are S, the compound is 
1-[2,4-dichloro-.beta.-(ethylthiolcarbonylthio)phenethyl]imidazole; 
7. When Z is O and X and Y are S, the compound is 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole; and 
8. When X, Y and Z are all S, the compound is 
1-[2,4-dichloro-.beta.-(ethylthiolthiocarbonylthio)phenethyl]imidazole. 
In naming the compounds of Formula (II) if R.sup.1 is 2,4-dichlorophenyl, 
the compound is named 
1-[2,4-dichloro-.beta.-(mercapto)phenethyl]imidazole. 
Utility, Formulation and Administration 
The subject compounds of Formula (I) exhibit anti-fungal and anti-bacterial 
activity. For example, compounds of the present invention exhibit 
anti-fungal activity against human and animal pathogens such as 
______________________________________ 
Microsporum audouini, 
Trichophyton rubrum, 
Microsporum gypseum, 
Trichophyton tonsurans, 
Microsporum gypseum-canis, 
Candida albicans, 
Epidermophyton floccosum, 
Cryptococcus neoformans, and 
Trichophyton mentagrophytes 
______________________________________ 
Compounds of the present invention represented by Formula (I) also exhibit 
antifungal activity against fungi of primarily agricultural importance 
such as 
______________________________________ 
Aspergillus flavus, 
Aspergillus niger, 
Cladosporium herbarum, 
Penicillium oxalicum, 
Fusarium graminearum, 
Penicillium spinulosum, and 
Penicillium notatum, 
Pithomyces chartarum. 
______________________________________ 
In addition, the compounds of the present invention represented by Formula 
(I) exhibit anti-bacterial activity against human and animal pathogens, 
such as 
______________________________________ 
Staphylococcus aureus, 
Proteus vulgaris, 
Streptococcus faecalis, 
Salmonella choleraesuis, 
Corynebacterium acnes, 
Pasteurella multocida, and 
Erysipelothrix insidiosa, 
Pseudomonas aeruginosa. 
Escherichia coli, 
______________________________________ 
Furthermore, compounds represented by Formula (I) exhibit anti-protozoal 
activity against certain human pathogens such as Trichomonas vaginalis. 
In view of the aforementioned activities, the subject compounds are found 
to be useful antimicrobials, having not only pharmaceutical but also 
agricultural and industrial application. 
Accordingly, a further aspect of the present invention relates to 
compositions for pharmaceutical, agricultural, and industrial use, which 
compositions comprise the subject compounds of Formula (I) in combination 
with a suitable carrier. A still further aspect of the present invention 
relates to methods of inhibiting the growth of fungi and bacteria by 
applying to a host object containing, or subject to attack by, fungi, 
protozoa, or bacteria, a fungicidally, protozoicidally, or bacteriocidally 
effective amount of a compound of Formula (I) or a suitable composition 
containing same. 
In pharmaceutical formulations compositions may be solid, semi-solid or 
liquid in form such as tablets, capsules, powders, suppositories, liquid 
solutions, suspensions, creams, lotions, gels, ointments and the like. 
Pharmaceutically acceptable non-toxic carriers, or excipients normally 
employed for solid formulations include tricalcium phosphate, calcium 
carbonate, kaolin, bentonite, talcum, gelatin, lactose, starch and the 
like; for semi-solid formulations there may be mentioned, for example, 
polyalkylene glycols, vaseline, petrolatum and other cream bases; for 
liquid formulations there may be mentioned, for example, water, oils of 
vegetable origin and low boiling solvents such as isopropanol, 
hydrogenated naphthalenes and the like. The pharmaceutical compositions 
containing the compounds of the present invention may be subjected to 
conventional pharmaceutical expedients such as sterilization and can 
contain conventional pharmaceutical excipients such as preservatives, 
stabilizing agents, emulsifying agents, salts for the adjustment of 
osmotic pressure and buffers. The compositions may also contain other 
therapeutically active materials. 
The pharmaceutical compositions of this invention typically comprise a 
pharmaceutically acceptable, non-toxic carrier in combination with one or 
more compounds represented by Formula (I) in an amount effective for 
relief or prevention of the specific condition being treated. Since the 
active compounds of this invention exhibit anti-fungal, anti-bacterial and 
anti-protozoal activity over a wide range of concentration, the effective 
amount may vary. For example, in topical formulations the amount may be 
about 0.1% by weight (%w) to about 10%w of the total pharmaceutical 
formulation while in other formulations the amount may be about 5 to 95%w 
or more. Preferably the pharmaceutical compositions of this invention are 
formulated in unit dosage form to facilitate administration (unit dosage 
being the amount of active ingredients administered on one occasion). 
In pharmaceutical applications, the subject compounds and compositions may 
be administered to humans and animals by conventional methods, e.g. 
topically, orally, parenterally and the like. "Topical" administration 
includes intravaginal application while parenteral administration includes 
intramuscular as well as subcutaneous and intravenous injection. 
Intravenous injection of imidazole derivatives for certain systemic 
conditions has been demonstrated to be effective (see for example, Drugs 
9, 419-420 (1975), which describes the intravenous administration of 
Miconazole, i.e. 
1-[2,4-dichloro-.beta.-(2',4'-dichlorobenzyloxy)phenethyl]imidazole 
nitrate, to patients with systemic candidiasis). Topical application is 
the preferred method of administration in pharmaceutical applications. For 
such treatment, an area having an existing fungal, protozoal or bacterial 
growth, or to be protected against attack by fungi, protozoa, or bacteria, 
may be treated with the subject compounds of Formula (I) or compositions 
by, for example, dusting, sprinkling, spraying, rinsing, brushing, 
dipping, smearing, coating, impregnating and the like. 
The exact regimen for pharmaceutical administration of the compounds and 
compositions disclosed herein will necessarily be dependent upon the needs 
of the individual subject being treated, the type of treatment, e.g., 
whether preventative or curative, the type or organism involved and, of 
course, the judgment of the attending practitioner. In general, for 
systemic (e.g., oral or parenteral) administration it is expedient to 
administer the active ingredient in amounts of between about 1 and 100 
mg/kg body weight per day (preferably between about 5 and 50 mg/kg. body 
weight per day) preferably distributed over several applications (e.g., in 
3 individual doses) in order to achieve effective results. For localized 
(e.g., topical) administration, however, proportionately less of the 
active ingredient is required. 
In agricultural applications, the subject compounds may be applied directly 
to plants (e.g., seeds, foliage) or to soil. For example, compounds of the 
present invention may be applied to seeds alone or in admixture with a 
powdered solid carrier. Typical powdered carriers are the various mineral 
silicates, e.g., mica, talc, pyrophyllite, and clays. The subject 
compounds may also be applied to the seeds in admixture with a 
conventional surface-active wetting agent with or without additional solid 
carrier. Surface-active wetting agents that can be used are any of the 
conventional anionic, non-anionic or cationic types. As a soil treatment 
for fungi and the like, the subject compounds can be applied as a dust in 
admixture with sand, soil or a powdered solid carrier such as mineral 
silicate with or without additional surface-active agent, or the subject 
compounds can be applied as an aqueous spray optionally containing a 
surface-active dispersing agent and a powdered solid carrier. As a foliage 
treatment, the subject compounds may be applied to growing plants as an 
aqueous spray which contains a surface-active dispersing agent with or 
without a powdered solid carrier and hydrocarbon solvents. 
In industrial applications, the subject compounds may be used to control 
bacteria and fungi by contacting the pathogens with the compounds in any 
known manner. Materials capable of supporting bacteria and fungi may be 
protected by contacting, mixing or impregnating these materials with the 
subject compounds. In order to increase their effect, the subject 
compounds may be combined with other pesticidal control agents such as 
fungicides, bactericides, insecticides, miticides and the like. A 
particularly important industrial/agricultural use for the subject 
compounds of the present invention is as a food preservative against 
bacteria and fungi which cause deterioration and spoilage of foods. 
PROCESS FOR PREING COMPOUNDS OF THE INVENTION 
Compounds of this invention represented by Forumula (I) may be prepared 
from several unique processes. For example these compounds may be prepared 
from (A) an alcohol or a suitable metal salt thereof, e.g., a 
1-[.beta.-hydroxyphenethyl]imidazole or its sodium salt, (B) a halide or 
reactive ester, e.g. a 1-(.beta.-halophenethyl)imidazole, or (C) from a 
mercaptan or a suitable metal salt thereof, i.e., a 
1-(.beta.-mercaptophenethyl)imidazole or its sodium salt. 
A. when starting from an alcohol such as a 1-[substituted-.beta.-hydroxy 
phenethyl]imidazole represented by Formula (III) or a suitable metal salt 
thereof, the alcohol (or salt) is reacted with a carbonyl chloride to give 
the desired product according to the equation set forth below 
##STR9## 
wherein R.sup.1, R, Y and Z have the values set forth hereinbefore. Note 
that a suitable salt of the compound of Formula (III) such as an alkali or 
alkaline earth metal salt, e.g. sodium, potassium or lithium salt may also 
be used. Thus, by reacting an R-oxycarbonyl chloride (Y and Z both O in 
IV, above) with the appropriate 1-[.beta.-hydroxyphenethyl]imidazole one 
obtains the corresponding 1-[.beta.-R-oxycarbonyloxy)phenethyl]imidazole. 
Similarly from the R-thiolcarbonyl chloride (Z is S and Y is O) one 
obtains the 1-[.beta.-(R-thiolcarbonyloxy)phenethyl]imidazoles, from the 
R-dithiocarbonyl chloride (Y and Z are both S) one obtains the 
1-[.beta.-(R-thiolthiocarbonyloxy)phenethyl]imidazole, and from the 
R-oxythiocarbonyl chloride (Z is O and Y is S) one obtains the 
1-[.beta.-(R-oxythiocarbonyloxy)phenethyl]imidazole. 
In carrying out the reaction of this process the 
1-[.beta.-hydroxyphenethyl]imidazole may be reacted directly with the 
carbonyl chloride in the presence of a base. Preferably when a 
thiocarbonyl chloride such as 
##STR10## 
is reacted, the base salt of the alcohol is the co-reactant. In the case 
of the reaction of the imidazole directly with the carbonyl or 
thiocarbonyl chloride, a suitable solvent is used for dissolving or 
suspending the reactants and a base may be added to aid in the reaction. 
Suitable solvents include dichloromethane, chloroform, pyridine, 
tetrahydrofuran, benzene, toluene, acetone, hexamethylphosphoramide, 
dimethylformamide and the like while suitable bases include (when needed) 
triethylamine, pyridine, potassium carbonate, 4-dimethylaminopyridine, and 
the like. 
Generally the temperature is about -20.degree. C. to 80.degree. C., 
preferably 0.degree.-30.degree. C. and the reaction is carried out at 
atmospheric pressure. At least 1 mole of the carbonyl chloride is reacted 
with 1 mole of the starting compound (III) for complete reaction to take 
place. Preferably the mole ratio of the carbonyl or thiocarbonyl chloride 
to compound (III) is between about 1:1 and 2:1. 
The starting compounds of Formula (III) may be prepared by a variety of 
reaction sequences, the most important of which will be discussed 
hereafter under "Preparations of Starting Materials". 
In some instances it is preferable to first form a salt of the 
1-[.beta.-hydroxyphenethyl]imidazole, e.g., before reaction with a 
thiocarbonyl chloride. For example, the sodium salt may be prepared by 
reacting the alcohol of Formula (III) with sodium hydride in a suitable 
solvent such as hexamethylphosphoramide, dimethylformamide, 
tetrahydrofuran and the like at a temperature of about 0.degree. to 
100.degree., generally about 10.degree. to 50.degree. C. Other suitable 
salts may be prepared by reacting the appropriate hydride, that is an 
alkali metal hydride or alkaline earth metal hydride with the 
1-[.beta.-hydroxyphenethyl]imidazole. Examples of these bases include 
potassium hydride, lithium hydride, calcium hydride, and the like. 
B. a method for preparing the compounds of this invention represented by 
Formula (I) where X is S and R is as previously defined (except optionally 
substituted phenyl) comprises reacting an appropriate compound of Formula 
(VI) with a suitable metal R-thiocarbonate, R-dithiocarbonate or 
R-trithiocarbonate salt. This reaction sequence can be depicted by the 
following equation: 
##STR11## 
wherein M is a suitable metal such as an alkali metal, e.g., sodium, 
potassium or lithium, or an alkaline earth metal; B is a reactive leaving 
group such as a tosylate, mesylate or halo, preferably chloro; and 
R.sup.1, Y and Z have the definitions presented hereinbefore. Thus by 
reacting a 1-[.beta.-halophenethyl]imidazole with, for example, an 
appropriate potassium-O-R thiocarbonate there is obtained the 
corresponding 1-[.beta.-(R-oxycarbonylthio)phenethyl] -imidazole, from 
potassium O-R dithiocarbonate is obtained the corresponding 
1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazole, and from the 
potassium hydrocarbyl trithiocarbonate compound is obtained the 
corresponding 1-[.beta.-(R-thiolthiocarbonylthio)phenethyl] -imidazole. In 
this series of reactions generally the reactants are placed in a suitable 
solvent such as an alcohol (e.g. methanol, ethanol) or acetone and are 
reacted at temperatures of from 0.degree. to 70.degree., generally under 
atmospheric conditions. The reactants may be present at mole ratios of 1 
to 3 moles of the carbonate per mole of the starting imidazole (VI). An 
acid salt of the imidazole of Formula (VI) may also be used if excess of 
the metal mono-, di-, or trithiocarbonate is employed. The starting 
imidazole depicted as Formula (VI) of this process may be prepared by 
methods known in the art such as those disclosed in U.S. Pat. No. 
3,679,697 to Kreider and Twelt. 
The R metal thiocarbonates may be prepared by methods disclosed in E. E. 
Reid, Organic Chemistry of Bivalent Sulfur, Vol. IV, Chemical Publishing 
Co., Inc., New York, New York (1962). As much of this disclosure as is 
pertinent is incorporated herein by reference. 
C. another process for making the compounds of Formula (I) wherein X is S 
involves reacting a compound of this invention of the Formula (II) or a 
suitable acid or base salt thereof with a suitable carbonyl or 
thiocarbonyl halide, preferably a carbonyl or thiocarbonyl chloride. A 
suitable base salt has a formula 
##STR12## 
A is a suitable metal such as an alkaline earth or preferably alkali metal 
such as lithium, potassium, or especially sodium and R.sup.1 is as 
previously defined. Thus, by reacting the mercaptide set forth in Formulae 
(II) or (IIa) above with at least one molar equivalent of an R-oxycarbonyl 
chloride, the corresponding 
1-[.beta.-(R-oxycarbonylthio)phenethyl]imidazole is obtained. Similarly, 
from R-thiolcarbonyl chloride, R-dithiocarbonyl chloride, and an 
R-oxythiocarbonyl chloride the corresponding 
1-[.beta.-(R-thiolcarbonylthio)phenethyl]imidazole, 
1-[.beta.-(R-thiolthiocarbonylthio)phenethyl]imidazole and 
1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazole are obtained 
respectively. 
It is to be understood that the compounds represented by Formulae (II) and 
(IIa) may be prepared and reacted in situ or they may be first prepared 
and isolated then reacted with the appropriate carbonyl or thiocarbonyl 
chloride. In this process the compounds represented by Formula (IIa) are 
prepared from a compound of this invention represented by Formula (I) such 
as a 1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazole or its acid salt 
as exemplified by 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole, by 
treating the compound with a suitable base such as sodium hydroxide 
preferably under an inert gas such as nitrogen at temperatures of about 
0.degree. C. to 50.degree. C., preferably about 20.degree.-25.degree. C. A 
mercaptide of Formula (IIa) may also be prepared by similarly treating a 
compound of PA 790, filed even date herewith represented by the formula. 
##STR13## 
wherein R, R.sup.1 and Y have the same definition as in this application, 
but R in addition may be H or styryl. The compounds of Formula (VII) are 
particularly valuable when Y is O. As much of PA 790 as is pertinent is 
incorporated herein by reference. The thiocarbonyl chlorides useful in the 
process of this invention may be prepared by methods set forth in E. E. 
Reid, Organic Chemistry of Bivalent Sulfur, Vol. IV, Chemical Publishing 
Co., Inc., New York, New York (1962) while the carbonyl chlorides are 
prepared by following methods generally known in the art, e.g. M. Matzner 
et al, Chemical Reviews, 64, 645-687 (1964). As much of these references 
as is pertinent is incorporated herein by reference. 
In the preparation of e.g., a mercaptide of Formula (IIa) wherein A is a 
suitable metal such as sodium, a compound of Formula (I) or an acid 
addition salt (e.g. oxalate of nitrate) wherein X is sulfur is reacted 
with a suitable metal hydroxide, e.g. an alkali metal hydroxide such as 
sodium hydroxide in a substantially inert solvent such as an oxygenated 
hydrocarbon, for example, methanol, at temperatures of about 0.degree. to 
50.degree. C. preferably about 20.degree. to 25.degree. to form e.g. the 
sodium thio salt. This salt may then be reacted with any suitable carbonyl 
chloride or thiocarbonyl chloride as discussed above to form the compounds 
of this invention represented by Formula (I) wherein X is S. The amount of 
alkali hydroxide needed for the reaction will depend in part on whether 
the compound represented by Formula (I) is a free base or the salt of a 
mono-basic acid (e.g. HNO.sub.3) or a di-basic acid (e.g. oxalic acid). If 
the compound of Formula (I) is a free base at least 2 equivalents of the 
alkali hydroxide are required, while at least 3 equivalents, and 
preferably 3-4, are required if the compound (I) is the salt of a 
monobasic acid and at least 4, preferably 4-5, equivalents of the alkali 
hydroxide if the compound (I) is the salt of a di-basic acid. 
Use of the Compounds of This Invention to Prepare Other Compounds 
This process is based on the realization that certain compounds of the 
Formulae (II) or (IIa) may be reacted with an appropriate hydrocarbyl 
halide to give certain compounds disclosed in U.S. Ser. No. 593,620 filed 
July 7, 1975 and PA 791, filed even date herewith, that is certain novel 
1-[.beta.-(R.sup.2 -thio)phenethyl]imidazoles represented by the formula 
##STR14## 
and the antimicrobial acid addition salts thereof, wherein 
R.sup.1 is defined hereinbefore and 
R.sup.2 is alkyl, alkenyl, aralkenyl, substituted aralkenyl, alkynyl, 
cycloalkyl, cycloalkyl alkyl, aralkyl, substituted aralkyl, or phenyl 
substituted with at least a nitro group at the 2- or 4-position, said 
substituted aralkenyl and substituted aralkyl containing at least one 
substituent on the aryl moiety selected from the group consisting of halo, 
lower alkyl, lower alkoxy, trifluoromethyl, nitro and cyano and said 
nitrophenyl optionally containing at least one other substituent selected 
from the group consisting of halo, lower alkyl, trifluoromethyl, nitro, 
and cyano. 
This process is based on the reaction between the compounds of Formula (II) 
or a suitable acid (base) salt thereof and a suitable hydrocarbyl halide 
such as that set forth in the following reaction: 
##STR15## 
wherein R.sup.1 and R.sup.2 are as defined hereinbefore and B is a 
suitable leaving group such as mesylate, tosylate, or halo, e.g. bromo or 
preferably chloro. 
Thus, one aspect of the process of this invention comprises preparing a 
compound of this invention represented by Formula (I) wherein X is S 
according to any of the processes set forth hereinbefore, converting this 
compound to a suitable compound represented by Formula (II), and reacting 
the latter compound with e.g. a suitable hydrocarbyl halide to form a 
compound of Formula (VIII). It is to be understood that the process may be 
carried out by (i) first forming a compound represented by Formula (II) or 
a suitable base salt thereof or (ii) by reacting a compound of Formula (I) 
(especially where X and Y are both S and Z is O) with a hydrocarbyl 
halide, (R.sup.2 B), and a suitable base. 
In the first case (i), a compound of this invention of Formula (I) or the 
acid addition salt, is reacted with a suitable base, e.g. an alkali metal 
hydroxide such as sodium hydroxide, potassium hydroxide or lithium 
hydroxide, and the like in a suitable solvent such as an oxygenated 
hydrocarbon e.g, methanol or ethanol, under an inert atmosphere for a time 
sufficient to convert the compound of this invention to the alkali metal 
base salt. Generally, this will take less than an hour at temperatures 
from 10.degree. to about 50.degree. C., preferably at about 15.degree. to 
25.degree. C. Once the alkali metal base salt is obtained it is reacted 
with a suitable compound represented by (R.sup.2 B) to give certain 
compounds of U.S. Ser. No. 593,620 or PA-791. The reaction between the 
R.sup.2 B and the alkali metal base salt generally takes place in the 
presence of a suitable solvent at reaction temperatures of about 0.degree. 
to 80.degree. C., normally around 25.degree.. Suitable solvents include 
methanol, ethanol, tetrahydrofuran, acetone and the like. 
In the second case (ii) a compound of Formula (I) is reacted with a 
hydrocarbyl halide, particularly a chloride, and a suitable base such as 
an alkali metal hydroxide, e.g. sodium or potassium hydroxide, in an 
appropriate solvent such as methanol, ethanol, tetrahydrofuran, acetone or 
the like. It is believed that in this case the reaction proceeds through 
the intermediacy of a compound of Formulae (II) or (IIa) which is formed 
in situ. The temperature will generally be between about 0.degree. and 
80.degree. C., preferably about 15.degree.-25.degree., the reaction being 
completed in about 1 hour or less. 
It has been further discovered that certain compounds of this invention of 
Formula (I) wherein X is S and Y and Z are O or S may be converted to the 
corresponding compound of Formula (VIII) having as the R.sup.2 group a 
moiety the same as the R of Formula (I) by heating an appropriate compound 
of Formula (I), wherein X is S, as the free base either alone or in a 
suitable inert solvent such as polar organic solvents (e.g. acetonitrile, 
dimethylformamide, dimethylsulfoxide, ethanol, and the like) or non-polar 
organic solvents, e.g. toluene, at a temperature sufficient to form a 
compound of Formula (VIII). Generally this elevated temperature may range 
between about 50.degree. C. and 200.degree. C., but preferably will be 
about 50.degree. to 100.degree. C. Preferably Z is oxygen; while Y may be 
oxygen or sulfur, it is preferably the latter. Generally, the reaction is 
completed in about 10 hours or less. 
Preparation of Starting Materials 
The following preparations are given to show one of skill in the art how to 
prepare the starting reactants for the process aspects of this invention. 
Reaction Scheme A 
In this reaction scheme the hydroxy compound of formula (III) is prepared 
by reduction of the corresponding ketone (IX) which in turn is prepared by 
reaction of an .alpha.-halo ketone with imidazole; 
##STR16## 
wherein Ha is chloro or bromo. 
Certain .alpha.-halo ketones are available; others may be readily prepared 
by methods known in the art, for example, by halogenation of the 
corresponding methyl ketone, from the Friedel-Crafts reaction or from acid 
halides, or enol ethers. 
The .alpha.-halo ketone (X) is contacted with imidazole preferably in an 
inert organic solvent to afford the keto imidazole of Formula (IX). The 
reaction is carried out utilizing at least a molar amount and, preferably, 
an excess of imidazole relative to halo ketone. The reaction may be 
carried out in the absence of solvent or, preferably, in an inert organic 
solvent such as, for example, dimethylformamide, hexamethylphosphoramide, 
acetonitrile, and the like. The reaction is suitably carried out at a 
temperature initially between about -10.degree. and 100.degree. C., most 
preferably between about 0.degree. and 25.degree. C. 
In the next step the keto imidazole of Formula (IX) is reduced to the 
hydroxy imidazole of Formula (III) utilizing a conventional metal hydride 
reducing agent such as, for example, sodium borohydride. The reaction is 
suitably carried out in an alcoholic solvent such as, for example, 
methanol or ethanol at a reduced temperature, for example, between about 
-10.degree. and +25.degree. C., most preferably about 0.degree. C. 
Other methods for preparing the 1-[.beta.-hydroxyphenethyl] imidazole (III) 
may be apparent to those skilled in the art, such as methods described in 
Godefroi et al, J. Med. Chem, 12, 784-791 (1966), and U.S. Pat. No. 
3,717,655 to Godefroi and Heeres. 
##STR17## 
In this reaction scheme the compound of Formula (III) is reacted with a 
thionyl halide of the formula SOHa.sub.2 such as thionyl chloride or 
thionyl bromide to form a compound of Formula (VI), wherein B is halo. A 
suitable solvent such as chloroform or dichloromethane can be added to 
promote contact between the reactants at 0.degree.-80.degree. C., 
generally about 20.degree. to reflux. The product can be isolated as the 
free base by evaporation of excess thionyl halide, addition of excess 
aqueous sodium or potassium carbonate, extraction with chloroform and 
removal of the solvent by vacuum distillation. Alternatively the product 
can be isolated as the corresponding hydrohalide salt by adding ethyl 
acetate or other inert liquid in which the salt is relatively insoluble 
q.s. precipitation.

EXAMPLES 
The following specific examples are given to enable those skilled in the 
art to more clearly understand the practice of the present invention. 
These examples should not be considered as a limitation upon the scope of 
the invention but merely as being illustrative and representative thereof. 
In the examples that follow, experimental conditions such as reaction 
times, temperatures, etc. may be varied as is apparent to one of skill in 
the art. In enumerating compounds in the following examples, it is to be 
understood that the names represent the compound itself as well as the 
antimicrobial acid addition salts thereof, such as the nitrate or oxalate. 
Where appropriate for identification purposes, a representative salt is 
given with the corresponding melting point. In the case of an oxalate 
salt, there is one oxalate per imidazole, i.e., the salt is represented as 
##STR18## 
EXAMPLE 1 
Preparation of 1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazoles 
A. preparation of 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonyl)thio)phenethyl] imidazole 
Twenty grams of 1-(.beta., 2,4-trichlorophenethyl)imidazole hydrochloride 
was added to 300 milliliters (ml) of absolute ethanol and 25 grams of 
anhydrous potassium ethyl xanthate. The mixture was stirred at room 
temperature for about 3 days until the reaction was complete as indicated 
by thin layer chromatography. The solvent was removed, water added and the 
product extracted with ether. The extracts were washed with water, dried 
over magnesium sulfate and the ether evaporated. The resulting oil was 
purified by chromatography on silicia gel eluting with 15% acetone in 
dichloromethane. The resulting oil was then dissolved in ether and an 
ethereal solution of oxalic acid was added dropwise until precipitation 
was complete. Recrystallization of the precipitate from acetone provides 
the oxalate salt of 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole as a 
white solid having a melting point of 122.5.degree.-124.degree. C. 
(foaming). 
B. preparation of other 1-[.beta.-(R-oxythiocarbonylthio)phenethyl] 
imidazoles 
Similarly by substituting other appropriate xanthates for potassium ethyl 
xanthate in part A of this example, the following imidazoles of this 
invention may be prepared, and, where indicated, may be characterized as 
the acid addition salts by treatment with the appropriate acid, e.g. 
nitric or oxalic: 
1-[2,4-dichloro-.beta.-(methoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(propoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(isopropoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-butoxythiocarbonylthio)phenethyl]imidazole as 
nitrate salt, mp 120.degree.-121.5.degree. C. (decomp.); 
1-[2,4-dichloro-.beta.-(isobutoxythiocarbonylthio)phenethyl] imidazole as 
nitrate salt, mp 148.5.degree.-150.degree. C. (decomp.); 
1-[2,4-dichloro-.beta.-(n-pentyloxythiocarbonylthio)phenethyl] imidazole; 
as nitrate salt, mp 118.5.degree.-119.5.degree. C. (decomp.) (foaming); 
1-[2,4-dichloro-.beta.-(isopentyloxythiocarbonylthio)phenethyl] imidazole; 
1-[2,4-dichloro-.beta.-(n-hexyloxythiocarbonylthio)phenethyl] imidazole; 
1-[2,4-dichloro-.beta.-(n-heptyloxythiocarbonylthio)phenethyl] imidazole; 
1-[2,4-dichloro-.beta. -(n-octyloxythiocarbonylthio)phenethyl] imidazole as 
nitrate salt, mp 107.degree.-113.degree. C. (decomp.-foaming); 
1-[2,4-dichloro-.beta.-(t-butoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(benzyloxythiocarbonylthio)phenethyl]imidazole as 
oxalate salt, mp 107.degree.-110.degree. C. (decomp); 
1[2,4-dichloro-.beta.-(p-fluorobenzyloxythiocarbonylthio)phenethyl]imidazol 
e; 
1-[2,4-dichloro-.beta.-(p-chlorobenzyloxythiocarbonylthio)phenethyl]imidazo 
le; 
1-[2,4-dichloro-.beta.-(p-bromobenzyloxythiocarbonylthio)phenethyl]imidazol 
e; 
1-[2,4-dichloro-.beta.-(p-methylbenzyloxythiocarbonylthio)phenethyl]imidazo 
le; 
1-[2,4-dichloro-.beta.-(3-phenyl-2-propenyloxythiocarbonylthio)phenethyl]im 
idazole; 
1-[2,4-dichloro-.beta.-(3-p-chlorophenyl-2-propenloxythiocarbonylthio)phene 
thyl]imidazole; 
1-[2,4-dichloro-.beta.-(o-chlorobenzyloxythiocarbonylthio)phenethyl]imidazo 
le; 
1-[2,4-dichloro-.beta.-(m-chlorobenzyloxythiocarbonylthio)phenethyl]imidazo 
le; 
1-[2,4-dichloro-.beta.-(2,4-dichlorobenzyloxythiocarbonylthio)phenethyl]imi 
dazole; 
1-[2,4-dichloro-.beta.-(3,4-dichlorobenzyloxythiocarbonylthio)phenethyl]imi 
dazole; 
1-[2,4-dichloro-.beta.-(cyclohexyloxythiocarbonylthio)phenethyl]imidazole 
as a nitrate salt, mp 139.5.degree.-140.5.degree. C. (decomp-foaming); 
1-[2,4-dichloro-.beta.-(cyclohexylmethoxythiocarbonylthio)phenethyl] 
imidazole; 
and the like. 
C. preparation of other imidazoles having different R.sup.1 substituents 
Similarly by substituting other 1-[.beta.-halophenethyl]imidazoles for 
1[.beta.,2,4-trichlorophenethyl]imidazole hydrochloride and other 
appropriate xanthates for ethyl xanthate in Part A of this example other 
compounds of this invention may be prepared such as the following: 
1[4-chloro-.beta.-(methoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-difluoro-.beta.-(n-butoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-fluoro-.beta.-(n-hexyloxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-(benzyloxythiocarbonylthio)phenethyl]imidazole; 
1[-4-methyl-.beta.-(isopropoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-trifluoromethyl-.beta.-(p-butoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dimethyl-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(p-chlorobenzyloxythiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(p-bromobenzyloxythiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-propoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(t-butoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-pentyloxythiocarbonylthio)phenethyl]imidazole; 
1-[4-bromo-.beta.-(p-chlorobenzyloxythiocarbonylthio)phenethyl]imidazole; 
1-[.beta.-(cyclohexyloxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-methoxythiocarbonylthio)phenethyl]imidazole; 
1[2,4,6-trichloro-.beta.-(n-propoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-(isopropoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole; 
1-[.beta.-(n-hexyloxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-(p-fluorobenzyloxythiocarbonylthio)phenethyl]imid 
azole; 
1-[2,4,6-trichloro-.beta.-(p-chlorobenzyloxythiocarbonylthio)phenethyl]imid 
azole; 
1-[2,4-dibromo-.beta.-(n-propoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dibromo-.beta.-(p-methylbenzyloxythiocarbonylthio)phenethyl]imidazol 
e; 
1-[2,4-dibromo-.beta.-(p-chlorobenzyloxythiocarbonylthio)phenethyl]imidazol 
e; 
1-[2,4-difluoro-.beta.-(n-pentyloxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-difluoro-.beta.-(n-hexyloxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-difluoro-.beta.-(p-chlorobenzyloxythiocarbonylthio)phenethyl]imidazo 
le; 
1-[2,4-dimethyl-.beta.-(n-pentyloxythiocarbonylthio)phenethyl]imidazole; 
1-[3,4-dichloro-.beta.-(n-propoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trimethyl-.beta.-(t-butoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-t-butyl-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-trifluoromethyl-.beta.-methoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trimethyl-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole as 
nitrate salt, mp 134.degree.-136.degree. C. (decomp-foaming); 
1-[4-t-butyl-2,6-dimethyl-.beta.-(methoxythiocarbonylthio)phenethyl]imidazo 
le, 
and the like. 
EXAMPLE 2 
Preparation of 1-[.beta.-(R-oxycarbonylthio)phenethyl]imidazoles 
A. preparation of 
1-[2,4-dichloro-.beta.-(n-octyloxycarbonylthio)phenethyl]imidazole 
By following the procedure set forth in Example 1, part A, but substituting 
S-potassium O-octyl thiocarbonate for potassium ethyl xanthate, 
1-[2,4-dichloro-.beta.-(n-octyloxycarbonylthio)phenethyl]imidazole may be 
prepared. The nitrate salt of the resulting oil is formed by dropwise 
addition of nitric acid (d = 1.42) to an ethereal solution of the 
imidazole until precipitation is complete. Filtration and 
recrystallization from ethyl acetate gives the nitrate salt having a 
melting point of 99.degree.-101.degree. C. 
B. by following the procedure set forth in part A of this example, but 
substituting other appropriate S-potassium O-hydrocarbyl thiocarbonates, 
other 1-[2,4-dichloro-.beta.-(R-oxycarbonylthio)phenethyl]imidazoles are 
prepared such as 
1-[2,4-dichloro-.beta.-(isopropoxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-propoxycarbonylthio)phenethyl]imidazole; 
and the like. 
C. other imidazoles of Formula (I) having different R.sup.1 substituents 
may be similarly prepared by substituting other 1-[.beta.-halo 
phenethyl]imidazoles for 1-[.beta.,2,4-trichlorophenethyl]imidazole 
hydrochloride and other S-potassium O-hydrocarbyl thiocarbonates for 
S-potassium O-octyl thiocarbonate in part A of this example. Other 
imidazoles of this invention include compounds such as: 
1-[4-chloro-.beta.-(isobutoxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-butoxycarbonylthio)phenethyl]imidazole; 
and the like. 
EXAMPLE 3 
Preparation of 1-[.beta.-(R-oxycarbonylthio)phenethyl]imidazoles 
A. preparation of 
1-[2,4-dichloro-.beta.-(n-butoxycarbonylthio)phenethyl]imidazole 
As an alternative to the process of Example 2, the following procedure, 
which is analagous to Example 5, may be used: 
To a solution of 0.16 g (4.0.times.10.sup..sup.-3 mole) of sodium hydroxide 
in 40 ml of anhydrous methanol under nitrogen was added 0.42 g 
(1.0.times.10.sup..sup.-3 mole) of 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole 
nitrate. After stirring for 45 minutes at room temperature, 1.0 g 
anhydrous potassium carbonate (K.sub.2 CO.sub.3) and 1 ml of n-butyl 
chloroformate were added and the mixture was stirred for 4 additional 
hours at room temperature under nitrogen. After removing the solvent in 
vacuo, water was added and the residue extracted with ether. The extracts 
were washed with water, dried (MgSO.sub.4) and the nitrate salt of 
1-[2,4-dichloro-.beta.-(n-butoxycarbonylthio)phenethyl]imidazole 
precipitated and recrystallized from ethyl acetate, mp 
112.5.degree.-114.5.degree. C. (decomp). 
B. by following a procedure similar to part A of this example, but 
substituting other R chloroformates for n-butyl chloroformate and using 
appropriate conditions, other 
1-[2,4-dichloro-.beta.-(R-oxycarbonylthio)phenethyl]imidazoles may be 
prepared, such as 
1-[2,4-dichloro-.beta.-(ethoxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-pentyloxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-hexyloxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-heptyloxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(2,4-dichlorophenoxycarbonylthio)phenethyl]imidazole 
1-[2,4-dichloro-.beta.-(3,4-dichlorophenoxycarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dichloro-.beta.-(p-chlorophenoxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorobenzyloxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(2,4-dichlorobenzyloxycarbonylthio)phenethyl]imidazo 
le; 
1-[2,4-dichloro-.beta.-(3,4-dichlorobenzyloxycarbonylthio)phenethyl]imidazo 
le; 
1-[2,4-dichloro-.beta.-(p-methylbenzyloxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(3-phenyl-2-propenyloxycarbonylthio)phenethyl]imidaz 
ole; 
and the like. 
C. other imidazoles of Formula (I) having different R.sup.1 substituents 
may be similarly prepared by substituting other 
1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazoles for 1-[2,4-dichloro 
-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole and other appropriate 
R-chloroformate for n-butyl chloroformate in part A of this example. These 
include 
1-[4-chloro-.beta.-(n-pentyloxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-hexyloxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-heptyloxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-octyloxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(3,4-dichlorophenoxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(2,4-dichlorophenoxycarbonylthio)phenethyl]- 
1-[4-chloro-.beta.-(p-methylphenylpropoxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(3,4-dichlorobenzyloxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(2,4-dichlorobenzyloxycarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(o-n-propylphenoxycarbonylthio)phenethyl]imidazole; 
1-[4-bromo-.beta.-(p-ethylbenzyloxycarbonylthio)phenethyl]imidazole; 
1-[.beta.-(n-decyloxycarbonylthio)phenethyl]imidazole; 
1-[2,4-dimethyl-.beta.-(3,4,5-trichlorophenoxycarbonylthio)phenethyl]imidaz 
ole; 
1-[4-t-butyl-.beta.-(3,4-methylbromophenoxycarbonylthio)phenethyl]imidazole 
and the like. 
EXAMPLE 4 
Preparation of 1-[.beta.-(phenoxythiocarbonylthio)phenethyl]imidazoles 
A. preparation of 
1-[2,4-dichloro-.beta.-p-chlorophenoxythiocarbonylthio)phenethyl]imidazole 
By following the procedure set forth in Example 3 but using 
O-p-chlorophenyl chlorothioformate in place of n-butyl chloroformate, and 
employing the appropriate reaction conditions, the nitrate salt of 
1-[2,4-dichloro-.beta.-(p-chlorophenoxythiocarbonylthio)phenethyl] 
imidazole is prepared. 
B. by substituting other appropriate O-phenyl chlorothioformates for 
p-chlorophenyl chlorothioformate in part A of this example and adjusting 
the reaction conditions as needed, other 
1-[2,4-dichloro-.beta.-(phenoxythiocarbonylthio)phenethyl]imidazoles may 
be prepared such as 
1-[2,4-dichloro-.beta.-(phenoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-fluorophenoxythiocarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dichloro-.beta.-(p-bromophenoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(3,4-dichlorophenoxythiocarbonylthio)phenethyl]imida 
zole; 
1-[2,4-dichloro-.beta.-(2,4-dichlorophenoxythiocarbonylthio)phenethyl]imida 
zole; 
1-[2,4-dichloro-.beta.-(m-chlorophenoxythiocarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dichloro-.beta.-(o-chlorophenoxythiocarbonylthio)phenethyl]imidazole 
; 
1-[2,4-.beta.-(p-methylphenoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(o-methylphenoxythiocarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dichloro-.beta.-(p-ethylphenoxythiocarbonylthio)phenethyl]imidazole; 
C. similarly, by following the procedure of parts A and B of this example 
but utilizing an appropriate substituted O-phenyl chlorothioformate and 
substituting another 1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazole 
of Formula (I) having a different R.sup.1 substituent for 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole, other 
compounds of this invention are prepared such as 
1-(2,4-.beta.-(phenoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-bromo-.beta.-(2,4-dichlorophenoxythiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(3,4-dichlorophenoxythiocarbonylthio)phenethyl]imidazole 
; 
1-[4-chloro-.beta.-(2,4-dichlorophenoxythiocarbonylthio)phenethyl] 
imidazole; 
1-[4-chloro-.beta.-(p-chlorophenoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-(p-fluorophenoxythiocarbonylthio)phenethyl]imidaz 
ole; 
1-[2,4,6-trichloro-.beta.-(phenoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-(p-chlorophenoxythiocarbonylthio)phenethyl]imidaz 
ole; 
1-[2,4-dibromo-.beta.-(p-chlorophenoxythiocarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trimethyl-.beta.-(p-chlorophenoxythiocarbonylthio)phenethyl]imidaz 
ole, 
and the like. 
EXAMPLE 5 
Preparation of 1-[.beta.-(R-thiolcarbonylthio)phenethyl]imidazoles 
A. 1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole 
oxalate (450 mg) prepared as described in Example 1, part A, was added 
under nitrogen to a stirred solution of 200 mg sodium hydroxide in 30 ml 
methanol at room temperature. Stirring was continued until the reaction 
was complete as indicated by thin layer chromatography (approximately 20 
minutes) and the resulting 1-[2,4-dichloro-.beta.-(sodium 
thio)-phenethyl]imidazole was reacted with a slight excess of 
t-butylthiolchloroformate by adding the chloroformate directly to the 
sodium salt solution. The mixture was stirred for 30 minutes, and the 
solvent removed by evaporation. Ether (150 ml) was added to the residue 
and the mixture was washed with three 30 ml portions of water, then dried 
over magnesium sulfate. The solution was then concentrated and treated 
with nitric acid (d = 1.42) until precipitation of the nitrate salt was 
complete. Recrystallization from ethyl acetate/acetone gave snow-white 
microcrystals of the nitrate salt of 
1-[2,4-dichloro-.beta.-(t-butylthiolcarbonylthio)phenethyl]imidazole, mp 
163.degree.-166.5.degree. (decomp.-foaming). 
B. by following the procedure set forth in part A of this example but 
employing the appropriately substituted R-thiol chloroformate in place of 
the t-butylthiolchloroformate other R-thiolcarbonylthio substituted 
compounds may be prepared. These compounds include the following: 
1-[2,4-dichloro-.beta.-(ethylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-propylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(isopropylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-butylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(isobutylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-pentylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-hexylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-heptylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorophenylthiolcarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dichloro-.beta.-(p-fluorophenylthiolcarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dichloro-.beta.-(phenylthiolcarbonylthio)phenethyl]imidazole as 
nitrate salt, mp 157.5.degree.-160.5.degree. C. (decomp.-foaming); 
1-[2,4-dichloro-.beta.-(2,4-dichlorophenylthiolcarbonylthio)phenethyl]imida 
zole; 
1-[2,4-dichloro-.beta.-(3,4-dichlorophenylthiolcarbonylthio)phenethyl]imida 
zole; 
1-[2,4-dichloro-.beta.-(benzylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-fluorobenzylthiolcarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dichloro-.beta.-(p-chlorobenzylthiolcarbonylthio)phenethyl]imidazole 
; and 
1-[2,4-dichloro-.beta.-(3-phenyl-2-propenylthiolcarbonylthio)phenethyl]imid 
azole. 
C. similarly, by utilizing compounds related to or the same as those set 
forth in Example 1, parts B and C, the corresponding sodium salts can be 
obtained and reacted with the appropriately substituted R-thiol 
chloroformate to yield other compounds of this invention such as: 
1-[4-chloro-.beta.-(n-butylthiolcarbonylthio)phenethyl]imidazole; 
1-[4-bromo-.beta.-(isopropylthiolcarbonylthio)phenethyl]imidazole; 
1-[4-fluoro-.beta.-(n-hexylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4,6-trichloro-.beta.-(phenylthiolcarbonylthio)phenethyl]imidazole; 
1-[2,4-dimethyl-.beta.-(p-chlorophenylthiolcarbonylthio)phenethyl]imidazole 
; and 
1-[4-t-butyl-.beta.-(ethylthiolcarbonylthio)phenethyl]imidazole. 
EXAMPLE 6 
Preparation of 1-[.beta.-(R-thiolthiocarbonylthio)phenethyl]imidazoles 
A. by following the procedure set forth in Example 1, part A, 
1-[2,4-dichloro-.beta.-(ethylthiolthiocarbonylthio)phenethyl]imidazole may 
be prepared by utilizing potassium ethyl trithiocarbonate in place of 
potassium ethyl xanthate and employing appropriate experimental 
conditions. 
B. compounds similar to those set forth in part A of this example may be 
prepared by this method as well by substituting the appropriate metal 
hydrocarbyl trithiocarbonate for the potassium ethyl xanthate of part A of 
Example 1. Compounds made by this method include the following: 
1-[2,4-dichloro-.beta.-(n-propylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-butylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(t-butylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-pentylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(isopropylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(benzylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-fluorobenzylthiolthiocarbonylthio)phenethyl]imida 
zole; and 
1-[2,4-dichloro-.beta.-(p-chlorobenzylthiolthiocarbonylthio)phenethyl]imida 
zole. 
C. similarly, by following the procedure set forth in Example 1, parts A 
and C, but employing 1-[.beta.-halophenethyl]imidazoles having different 
R.sup.1 substituents in place of the 
1-[.beta.,2,4-trichlorophenethyl]imidazole hydrochloride of part A of 
Example 1 and utilizing the appropriate metal hydrocarbyl trithiocarbonate 
similar to those of Example 6, part B, in place of potassium ethyl 
xanthate of Example 1, part A, the following compounds are prepared: 
1-[.beta.-(t-butylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(p-fluorobenzylthiolthiocarbonylthio)phenethyl]imidazole 
; 
1-[4-chloro-.beta.-(p-chlorobenzylthiolthiocarbonylthio)phenethyl]imidazole 
; 
1-[4-chloro-.beta.-(ethylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-propylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(ethylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(n-propylthiolthiocarbonylthio)phenethyl]imidazole; 
Alternative route to 
1-[.beta.-(R-thiolthiocarbonylthio)phenethyl]imidazoles 
A. preparation of 
1-[2,4-dichloro-.beta.-(methylthiolthiocarbonylthio)phenethyl]imidazole 
By following the procedure set forth in Example 3 but using methyl 
chlorodithioformate in place of n-butyl chloroformate, and employing the 
appropriate reaction conditions, the nitrate salt of 
1-[2,4-dichloro-.beta.-(methylthiolthiocarbonylthio)phenethyl]imidazole is 
prepared. 
B. by substituting other appropriate R chlorodithioformates for methyl 
chlorodithioformate in part A of this example and adjusting the reaction 
conditions as needed, other 
1-[2,4-dichloro-.beta.-(R-thiolthiocarbonylthio)phenethyl]imidazoles may 
be prepared such as 
1-[2,4-dichloro-.beta.-(ethylthiolthiocarbonylthio]imidazole; 
1-[2,4-dichloro-.beta.-(phenylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-fluorophenylthiolthiocarbonylthio)phenethyl]imida 
zole; 
1-[2,4-dichloro-.beta.-(p-chlorophenylthiolthiocarbonylthio)phenethyl]imida 
zole; 
and the like. 
C. similarly, by following the procedure of parts A and B of this example 
but utilizing an appropriate R chlorodithioformate and substituting 
another 1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazole of formula 
(I) having a different R.sup.1 substituent for 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole, other 
compounds of this invention may be prepared such as 
1-[4-chloro-.beta.-(methylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(ethylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(phenylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-bromo-.beta.-(ethylthiolthiocarbonylthio)phenethyl]imidazole; 
1-[4-chloro-.beta.-(p-chlorophenylthiolthiocarbonylthio)phenethyl]imidazole 
; 
1-[2,4-dimethyl-.beta.-(p-bromophenylthiolthiocarbonylthio)phenethyl]imidaz 
ole; 
1-[4-chloro-.beta.-(p-fluorophenylthiolthiocarbonylthio)phenethyl]imidazole 
and the like. 
EXAMPLE 8 
Preparation of 1-[.beta.-(R-oxycarbonyloxy)phenethyl]imidazoles 
A. a solution of 0.8g (4.86 .times. 10.sup.-.sup.3 moles) of 
n-hexylchloroformate in 10 ml of dry tetrahydrofuran was added dropwise to 
a 0.degree. C. solution of 1.0 g (3.98 .times. 10.sup.-.sup.3 moles) of 
1-[.beta.-hydroxy-2,4-dichlorophenethyl]imidazole, 2 ml of triethylamine, 
and 30 ml of dry tetrahydrofuran over a period of 10 minutes. After 
stirring the resulting white suspension for 2 hours at room temperature, 
the solvent was removed, water added and the solution extracted with 
ether. The extracts were washed with water, dried (MgSO.sub.4) and the 
nitrate salt precipitated by dropwise addition of concentrated nitric acid 
(d = 1.42) until precipitation was complete. After filtering, 0.62g of the 
nitrate salt of 
1-[2,4-dichloro-.beta.-(n-hexyloxycarbonyloxy)phenethyl]imidazole, was 
recrystallized from ethyl acetate/ethanol, mp 108.degree.-112.degree. C. 
(decomp). 
B. by following the procedure set forth in part A of this example but 
employing a different hydrocarbyl chloroformate, other compounds of this 
invention may be prepared, such as: 
1-[2,4-dichloro-.beta.-(n-butoxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-pentyloxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-heptyloxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-octyloxycarbonyloxy)phenethyl]imidazole as 
nitrate salt, mp 92.5.degree.-95.5.degree. C. (decomp). 
1-[2,4-dichloro-.beta.-(n-nonyloxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(3-p-chlorophenylpropoxycarbonyloxy)phenethyl]imidaz 
ole; 
1-[2,4-dichloro-.beta.-(2,4-dichlorophenoxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorophenoxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorooxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(3,4-dichlorobenzyloxycarbonyloxy)phenethyl]imidazol 
e; and 
1-[2,4-dichloro-.beta.-(2,4-dichlorobenzyloxycarbonyloxy)phenethyl]imidazol 
e. 
C. by following the procedure of part A of this example but employing a 
different hydrocarbyl chloroformate as well as a different 
1-(.beta.-hydroxyphenethyl)imidazole, other compounds of this invention 
may be prepared, such as: 
1-[4-chloro-.beta.-(n-heptyloxycarbonyloxy)phenethyl]imidazole; 
1-[4-chloro-.beta.-(cyclopentylmethoxycarbonyloxy)phenethyl]imidazole; 
1-[4-bromo-.beta.-(cycloocytylethoxycarbonyloxy)phenethyl]imidazole; 
1-[4-chloro-.beta.-(p-chlorophenoxycarbonyloxy)phenethyl]imidazole as 
oxalate salt, mp 152.degree.-152.5.degree. C. (decomp.-foaming); 
1-[.beta.-(3-p-tert-butylphenylpropoxycarbonyloxy)phenethyl]imidazole; 
1-[4-trifluoromethyl-.beta.-(2,4-dichlorophenoxycarbonyloxy)phenethyl]imida 
zole; 
1-[4-t-butyl-.beta.-(p-chlorophenoxycarbonyloxy)phenethyl]imidazole; 
1-[2,4-dimethyl-.beta.-(2,4,6-trichlorophenoxycarbonyloxy)phenethyl]imidazo 
le; 
1-[.beta.-(n-dodecyloxycarbonyloxy)phenethyl]imidazole; 
1-[4-chloro-.beta.-(p-tert-butylphenoxycarbonyloxy)phenethyl]imidazole; 
1-[4-fluoro-.beta.-(p-tert-butylbenzyloxycarbonyloxy)phenethyl]imidazole; 
and the like. 
EXAMPLE 9 
Preparation of 1-[.beta.-(R-oxythiocarbonyloxy)phenethyl]imidazoles 
A. two hundred forty (240) mg of a dispersion of 56% w sodium hydride in 
mineral oil is added to 1.30g of 
1-[2,4-dichloro-.beta.-hydroxyphenethyl]imidazole in 10 ml. 
hexamethylphosphoramide under nitrogen and the mixture stirred at 
10.degree.-25.degree. C. for 1 hour and at 50.degree. C. for a further 1 
hour. The resulting solution is then cooled to ca. 5.degree. C. and 
treated dropwise with 685mg. of O-ethyl chlorothioformate and the mixture 
stirred 1 hour at room temperature and at 40.degree. for 1-2 hours. The 
mixture is poured into water, extracted with ether and the extracts washed 
with water, dried over magnesium sulfate and evaporated. The product is 
purified by chromatography on silica gel eluting with 10-15% acetone in 
dichloromethane. 
The oxalate salt is precipitated by addition of ethereal oxalic acid to the 
product in ether until precipitation is complete. Recrystallization from 
ethyl acetate/acetone gives crystals of 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonyloxy)phenethyl]imidazole oxalate. 
B. by following the procedure of part A of this example but employing other 
appropriate O-hydrocarbyl chlorothioformates, the following products may 
be prepared: 
1-[2,4-dichloro-.beta.-(n-propoxythiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-butoxythiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-pentyloxythiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-hexyloxythiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-heptyloxythiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorophenoxythiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(2,4-dichlorophenoxythiocarbonyloxy)phenethyl]imidaz 
ole; 
1-[2,4-dichloro-.beta.-(3,4-dichlorophenoxythiocarbonyloxy)phenethyl]imidaz 
ole; 
1-[2,4-dichloro-.beta.-(p-chlorobenzyloxythiocarbonyloxy)phenethyl]imidazol 
e; 
1-[2,4-dichloro-.beta.-(2,4-dichlorobenzyloxythiocarbonyloxy)phenethyl]imid 
azole; and 
1-[2,4-dichloro-.beta.-(3,4-dichlorobenzyloxythiocarbonyloxy)phenethyl]imid 
azole. 
C. similarly, by following the procedure of part A of this example but 
employing 1-[.beta.-hydroxyphenethyl]imidazoles of Formula (III) having 
different R.sup.1 substituents and also employing different O-hydrocarbyl 
chlorothioformates, the following compounds are prepared: 
1-[4-t-butyl-.beta.-(p-chlorobenzyloxythiocarbonyloxy)phenethyl]imidazole; 
1-[.beta.-(2,3,4,5,6-pentachlorophenoxythiocarbonyloxy)phenethyl]imidazole; 
1-[4-chloro-.beta.-(2,4-dichlorophenoxythiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dibromo-.beta.-(ethoxythiocarbonyloxy)phenethyl]imidazole; 
and the like. 
EXAMPLE 10 
Preparation of 1-[.beta.-(R-thiolthiocarbonyloxy)phenethyl]imidazoles 
A. by a similar procedure to that described in Example 9, part A, the 
sodium salt of 1-[2,4-dichloro-.beta.-hydroxyphenethyl]imidazole is 
prepared which is then reacted with methyl chlorodithioformate to form 
1-[2,4-dichloro-.beta.-(methylthiolthiocarbonyloxy)phenethyl]imidazole. 
B. by substituting other appropriate hydrocarbyl chlorodithioformates for 
methyl chlorodithioformate in part A of this example, the following 
compounds may be prepared: 
1-[2,4-dichloro-.beta.-(ethylthiolthiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-propylthiolthiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-butylthiolthiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-pentylthiolthiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-hexylthiolthiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(n-heptylthiolthiocarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorophenylthiolthiocarbonyloxy)phenethyl]imidaz 
ole; 
1-[2,4-dichloro-.beta.-(p-fluorophenylthiolthiocarbonyloxy)phenethyl]imidaz 
ole; and 
1-[2,4-dichloro-.beta.-(p-chlorobenzylthiolthiocarbonyloxy)phenethyl] 
imidazole. 
C. similarly, by following the procedure of part A of this example but 
employing a 1-[.beta.-hydroxyphenethyl]imidazole of Formula (III) having 
different R.sup.1 substituents and also employing different hydrocarbyl 
chlorodithioformates, the following compounds are prepared: 
1-[4-t-butyl-.beta.-(p-chlorobenzylthiolthiocarbonyloxy)phenethyl] 
imidazole; 
1-[.beta.-(2,3,4,5,6-pentachlorophenylthiolthiocarbonyloxy)phenethyl] 
imidazole; 
1-[4-chloro-.beta.-(2,4-dichlorophenylthiolthiocarbonyloxy)phenethyl] 
imidazole; 
1-[2,4-dibromo-.beta.-(ethylthiolthiocarbonyloxy)phenethyl] imidazole; 
and the like. 
EXAMPLE 11 
Preparation of 1-[.beta.-(R-thiolcarbonyloxy)phenethyl] imidazoles 
A. by following the procedure of Example 9, part A, the sodium salt of 
1-[2,4-dichloro-.beta.-hydroxyphenethyl]imidazole is prepared which is 
then reacted with S-ethyl chlorothioformate to form 1-[2,4 
-(ethylthiolcarbonyloxy)phenethyl] imidazole. 
B. by substituting other appropriate S-hydrocarbyl chlorothioformates for 
S-ethyl chlorothioformate in part A of this example, the following 
compounds may be prepared: 
1-[2,4-dichloro-.beta.-(n-propylthiolcarbonyloxy)phenethyl] imidazole; 
1-[2,4-dichloro-.beta.-(n-butylthiolcarbonyloxy)phenethyl] imidazole; 
1-[2,4-dichloro-.beta.-(n-pentylthiocarbonyloxy)phenethyl] imidazole; 
1-[2,4-dichloro-.beta.-(n-hexylthiolcarbonyloxy)phenethyl] imidazole; 
1-[2,4-dichloro-.beta.-(n-heptylthiolcarbonyloxy)phenethyl] imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorophenylthiolcarbonyloxy)phenethyl imidazole; 
1-[2,4-dichloro-.beta.-(2,4 
-dichlorophenylthiolcarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(3,4 
-dichlorophenylthiolcarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(p-fluorophenylthiolcarbonyloxy)phenethyl] 
imidazole; 
1-[2,4-dichloro-.beta.-(p-chlorobenzylthiolcarbonyloxy)phenethyl]imidazole; 
1-[2,4-dichloro-.beta.-(2,4 
-dichlorobenzylthiolcarbonyloxy)phenethyl]imidazole; and 
1-[2,4-dichloro-.beta.-(3,4 
-dichlorobenzylthiolcarbonyloxy)phenethyl]imidazole. 
C. similarly, by following the precedure of part A of this example but 
employing a 1-[.beta.-hydroxyphenethyl]imidazole of Formula (III) having 
different R.sup.1 substituents and also employing different S-hydrocarbyl 
chlorothioformates, other compounds such as the following may be prepared: 
1-[4-t-butyl-.beta.-(p-chlorobenzylthiolcarbonyloxy)phenethyl]imidazole; 
1-[.beta.-(2,3,4,5,6-pentachlorophenylthiolcarbonyloxy)phenethyl]imidazole; 
and the like. 
EXAMPLE 12 
Cleavage of an Acid Salt to a Free Base 
The oxalate salt of 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole is 
prepared according the process set forth in Example 1, part A. Two g of 
this salt suspended in 100 ml of dichloromethane is shaken with excess 
dilute potassium carbonate solution until the salt is completely 
dissolved. The organic layer is then separated, washed twice with water, 
and dried over magnesium sulfate. The solvent is then evaporated to yield 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole in base 
form as an oil. 
In a similar manner, the acid addition salts of all compounds of Formula 
(I), particularly those representatives in Examples 1-11, can be converted 
to the corresponding compounds in base form. 
EXAMPLE 13 
Acid Salt Formation from a Free Base 
Nitric acid (d=1.42) was added dropwise to a stirred solution of 500 mg. of 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole in 30 
ml anhydrous ether until precipitation was complete. The product was 
filtered off, washed with ether, air dried, and recrystallized from ethyl 
acetate/acetone to yield 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole 
nitrate, mp 142.5.degree.-143.degree. C. (foaming). 
In similar manner, all compounds of Formula (I) in free base form can be 
converted to the acid addition salts by treatment with the appropriate 
acid, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, 
nitric acid, phosphoric acid, acetic acid, propionic acid, glycolic acid, 
lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, malic 
acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 
cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 
or p-toluenesulfonic acid. 
EXAMPLE 14 
The following example is included to illustrate the preparation of 
representative formulations which may be used to control fungi, protozoa 
or bacteria in humans and animals. 
______________________________________ 
A. Topical Formulation 
______________________________________ 
grams 
______________________________________ 
Active compound 0.2 - 2 
Span 60 2 
Tween 60 2 
Mineral oil 5 
Petrolatum 10 
Methyl paraben 0.15 
Propyl paraben 0.05 
BHA(butylated hydroxy anisole) 
0.01 
Water qs 100 
______________________________________ 
All of the above ingredients, except water, are combined and heated at 
60.degree. C. with stirring. A sufficient quantity of water at 60.degree. 
C. is then added with vigorous stirring to provide 100 g. of the cream 
formulation which is then cooled to room temperature. 
______________________________________ 
B. I.V. Formulation 
______________________________________ 
Active compound 0.5 g. 
Propylene glycol 20 g. 
Polyethylene glycol 400 
20 g. 
Tween 80 1 g. 
0.9% Saline solution qs 
100 ml. 
______________________________________ 
The active compound is dissolved in propylene glycol, polyethylene glycol 
400 and Tween 80. A sufficient quantity of 0.9% saline solution is then 
added with stirring to provide 100 ml. of the I.V. solution which is 
filtered through a 0.2 micron membrane filter and packaged under sterile 
conditions. 
______________________________________ 
C. Oral Formulation 
______________________________________ 
parts by weight 
______________________________________ 
Active compound 200 
Magnesium stearate 3 
Starch 30 
Lactose 116 
PVP (polyvinylpyrrolidone) 
3 
______________________________________ 
The above ingredients are combined and granulated using methanol as the 
solvent. The formulation is then dried and formed into tablets (containing 
200 mg. of active compound) with an appropriate tabletting machine. 
EXAMPLE 15 
Preparation of 1-[.beta.-(R-thio)phenethyl]imidazoles 
A. preparation of 
1-[2,4-dichloro-.beta.-(4-chlorobenzylthio)phenethyl]imidazole, nitrate 
850 Milligrams of 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole nitrate 
was added to a solution of sodium hydroxide (330 mg) in 30 ml. methanol 
under nitrogen and the mixture stirred at room temperature for about 30 
minutes until no carbonate remained as indicated by thin layer 
chromatography. To the resulting solution 350 mg. of 
.alpha.,p-dichlorotoluene was added, and the mixture stirred for 30 
minutes before removal of the solvent under reduced pressure. Ether and 
water were then added to the residue and the extract washed with water and 
dried over magnesium sulfate. Dropwise, addition of nitric acid (d = 1.42) 
to the ethereal solution precipitated the nitrate salt of 
1-[2,4-dichloro-.beta.-(4-chlorobenzylthio)phenethyl]imidazole, mp 
130.5.degree.-132.degree. C. when recrystallized from acetone. 
B. by following a procedure similar to that set forth in part A of this 
example, but substituting n-heptyl bromide and 
.alpha.,2,4-trichlorotoluene for .alpha.,p-dichlorotoluene, the following 
respective compounds are prepared: 
1-[2,4-dichloro-.beta.-(n-heptylthio)phenethyl]imidazole oxalate. mp 
106.degree.-109.degree. C. and 
1-[2,4-dichloro-.beta.-(2,4-dichlorobenzylthio)phenethyl]imidazole nitrate, 
mp 133.5.degree.-134.5.degree. C. 
C. by following a procedure similar to that set forth in parts A and B of 
this example but substituting other 
1-[.beta.-(R-oxythiocarbonylthio)phenethyl]imidazoles or 
1-[.beta.-(R-oxycarbonythio)phenethyl]imidazoles, 
1-[.beta.-(R-thiolcarbonylthio)phenethyl]imidazoles, or 
1-[.beta.-(R-thiolthiocarbonylthio)phenethyl]imidazoles for 
1-[2,4-dichloro-.beta.-(ethoxythiocarbonylthio)phenethyl]imidazole and 
other appropriate R.sup.2 halides for .alpha.,p-dichlorotoluene, the 
corresponding 1-[R.sup.1 -.beta.-(R-thio)phenethyl]imidazoles are 
obtained.