JPS60260588A - Preparation of organophosphoroimidazolide compound and organophosphoro-1,2,4-triazolide compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful for the production of a phosphoric acid triester compound having relation to insecticide, phospholipid and nucleic acid chemistry, easily, by reacting a specific organophosphorochloridate compound with an organotin compound. CONSTITUTION:The objective compound of formula III can be produced by reacting (A) the organophosphorochloridate compound of formula I (R<1> is alkyl or aryl; n is 1 or 2) (e.g. dimethyl chlorophosphate) with (B) usually 1-2 times equivalent of an organotin compound of imidazole or 1,2,4-triazole of formula II (R<2> is alkyl or aryl; X is imidazolyl or 1,2,4-triazolyl) (e.g. triethylstannyl imidazole), in an organic solvent such as methylene chloride, usually at 0-35 deg.C.

Description

[Detailed Description of the Invention] Industrial Application Fields Phosphate triester compounds are related to pesticides, phospholipids, and nucleic acid chemistry, and their production methods are being actively researched. The present invention relates to a method for producing an intermediate for producing a triester compound.

Conventional technology One of the methods for producing phosphoric acid ester compounds is based on the reaction formula (
As shown in 1), there is a method in which an organophosphoroimidazolyl compound or an organophosphoroimidazolyde compound represented by the general formula [Kawa] is reacted with an alcohol.

[■] [■] (In the formula, R is an alkyl group or an aryl group, and X is an imidazolyl group or /, J, 4'-) riazolyl group B
5 represents an alkyl group, a cycloalkyl group or a deoxynucleosyl group, and n represents 1 or 2. ) for the use of imidazoli r compounds, see for example J. Bad.
diley, J., G., Buchanan and R.
, Letters, J., Ohem, Soc., J.
#/ko(lR6), also/ , , 7. , G-
Regarding the use of triazolyl compounds, for example, N, Ka
tagiri, K. Itakura and S.A.
, Narag, J., Am., Ohem, SOc.
, , ri7°/33λ (t 51 qs).

This reaction is useful as a method for producing phosphoric acid triester in that there are few side reactions.

As is already known, the compound represented by the general formula [1ll] can be reacted with the linked chloride P compound represented by the general formula [■] in an organic solvent such as tetrahyP-profuran or /, tI-dioxane. -2 equivalents of imidazole or <'H-i +2. It can be produced by reacting q-triazole with q-triazole in the presence of a base such as triethylamine according to reaction formula (2). (For example, see the above literature).

1 (R'0)5-nPOtn + nHX + nNR,
-(1) 1 (R' O) 5-nPXn + n HCt"N'
2 (21 (IIIJ (wherein, R',
Separate the hydrochloride of a base such as triethylamine as a by-product, and
The compound (Ill) contained in the ν liquid is generally reacted with alcohol as shown in the reaction formula (1).

Problems to be Solved by the Invention However, since compound (III) is unstable in water and heat, when producing compound (III) by this method, reaction operations such as p-passage of the hydrochloride of the base are necessary. The compound inside (
m) Care must be taken to avoid decomposition.

In view of the state of the prior art as described above, the present inventors
As a result of searching for a simple method for producing the compound (In),
We have discovered that this object can be advantageously achieved by reacting the organophosphorochloridate compound represented by the general formula (1) with the organotin compound represented by the general formula [■] according to the reaction formula (3). Ta.

(3) (1) (II) (Ill) [fV,) (wherein R is an alkyl group or an aryl group, R2 is an alkyl group or an aryl group, X is an imidazolyl group or/, 2.Q
- (a riazolyl group, n is 1 or λ) According to the present invention, the organic group 1 of the organophosphorochloridate compound represented by the general formula CI) is any alkyl group or alihylic group. fI- is a methyl group, ether group, n-butyl group, co*, Z*I
2-chloroethyl group, phenyl group % p-/lorophenyl group al-c. - Can open chlorophenyl group, etc. These compounds can be produced by known methods from phosphorus oxychloride and the corresponding alcohol (IILloH), but some are commercially available and can also be used. imidazole and l.

2. Examples of the organic group R1 of the triorganostannyl derivative of a-triazole include methyl group, ethyl group, n-butyl group, and phenyl group. The compound represented by the general formula (II), in which an alkyl group such as -dityl group is preferable, is described by Lujten et al. (Brec, Trsv
, Ohrm, , J', 2. //J'/(/PJJ)
) (If you combine 4 and 2, you will get 4.

The object of the method of the present invention, the organophosphoroimidazoly-P compound and the organophosphoroimidazoly-P compound represented by the general formula (Ill) Compound (1) K in medium
On the other hand, the reaction, which can be quantitatively produced by incubating at a reaction temperature of 0 to 35°C using e/2 times the equivalent of compound (If), proceeds quickly, so consideration should be given to the Fi sum when determining the reaction time. There's no need to do it (10 minutes is enough.

The compound represented by the general formula [m] cannot be isolated because it is unstable to water and heat.

'HNMR or 'ON
The two general formulas (I
The compound represented by II) can be used directly in the production of a phosphoric triester compound according to reaction formula (1) without isolation.

For example, according to the process of the invention, dimethylchlorophosphate and 1 equivalent of triethylstannyl/
, J, <t-) Riazole After reacting in trachloroform for 10 minutes, 1 volume of methanol was added to the resulting reaction mixture and stirred for 1 hour, resulting in a yield of 51s% according to reaction formula (1). Trimethyl phosphate is obtained.

EXAMPLES The present invention will be explained in detail with reference to Examples below, but the present invention is not limited to these Examples.

Example 1 CI') (n') (In') (fV') yo<dried triethylsta/nilimitasol [1') (0,0
9!3fP, 0. ．． 3Ji Lee-r:k) f Dissolved in deuterated chloroform (0,34m) and dimethyl chlorophosphate ([') (o, oho 6t.

0.03 rd, 0.33 mmol) was added slowly with stirring. After stirring this solution at room temperature for 10 minutes, its NMR was measured.

'HNM几(00015,TM8) δ: 0.70
- /, 90 (m s/!; H, /, s (o2H5)5sna1) including -M line at 30.

3.90 (d, 6H, J=/s, OHt,, OH, 0)
.

7.2.0-7.3! (m, , ZH, imidazolyl group.

8), 7.73-7, g j (m, /H, imidazolyl group-2 position) ppm.

”ONMR (ODOI, , TMs) δ: / (7
,,? (5n(OH20H,),).

//, / (5n(OH20Hs)5), j ”-
9,! ! , 2 (9H, 0).

t Jl □, 7, t J /,, 2 (imidazolyl group) ppm-Example 2 Triethylstannyl-'*J*''-t!j
Azole (i[') (0,0? s y y, o
, as mmol) as chloroform (o,, y-)
dimethyl poo x p (i'
), (o, ohoa t.

0.03twd, 0. ．． 3Ji mol) was added. The solution was stirred at room temperature for 5 minutes, and its NMR was measured.

'HNMIL(0001,,TM8)δ: 0.7 o
-/, Rio (m.

/3H, including singlet at 1, 30, (02H5)5S
nOI).

3, r u (d, A H, J ”= / u, O
Hz, 0! (50).

♂, O9 (d, ZH, J=J, oHz, / ,
J, Q-triazolyl group-3 position) t, jO-/
,jj(m.

ZH, l, co, Hiro-triazolyl group -j position > ppm.

Example? CI') CI') (In") (IV' cotriethylstannyl/, J, &-triazole (If') (
0,09! ;? ? , 0.33 mmok) and diphenylchlorophos 7ate (:i') (o, o P4t
.

? + (), 073 M + 0.3j mmol)
were reacted in deuterated chloroform (0,3t-) in the same manner as in Example 2 to obtain diphenylphosphoro-/, J, 4'-
) liazolide [m'] and triethylstannyl)' (
■' ) got.

'HNM11'L (ODOI3, TMS) δ:
o, to-8ri0 (m.

/JH, /, s containing a singlet in GO (02F15)
5 S n 01 ) %6.73-7.4'O(m
, 10H, Ph), g, os(d.

JH, J=J, □Hz, /, J, Q-triazolyl group-
3rd place) %L30-1. ! ;j (rn, JH, l, 2゜darazolyl group-3 position) ppm.

"ONMI' ((ODOI5. TMS) δ: 9-"
(Sn(OH20H).

? ,? (8n(OH20H5)3) , / J O,
/ , / J O,,? .

/ J6. ! ,/ ,,? 0.1, / g ta, o, / tt 9. a (Ph).

lso,,z,tso,t,lss,l,tss,
r(t.

2,/l-triazolyl group) ppm.

Example q (1'l (II') [111'') (fV') Triethyl stannyl imitasol [lT') (0,OriJ
,! f, 0.3 mmol) and 7 m2A.

Chlorophosphate (1') (o, o9ao?.

0.073ml, 0. ．． 3 j mmol) was reacted in 1 weight o o form (o,,?smt) in the same manner as in Example.

diphenylphosphoroimidazolypcr) and triethylstannyl)'(IV') ti7t.

'HNMR (ODOI, , TMS) δ: 0.70
- /, tOl(m.

/jH, (02p5)5sn) , a, to-q, a
o(m, t, 2H, Ph, imidazolyl group -<<,
j position), 7.737, Zj (m, / H, imidazolyl group-2 position) ppm.

Example! [:I'] (II') Triethylstannyl-72<-IJ azole (0
, / 7 / , rs', 0.7 mmol) with a weight o.

Dissolve in A, A (0,33-) and add 0-chlorophenyldichlorophosphate (0,0zaj???.

After gradually adding 0.0 j 6 ml, 0.3 j mmol) and stirring at room temperature for 13 minutes, the solution was analyzed by NMR.
was measured.

1HNM几(00015,TMS)δ: 0.7 o
-／、? o (hat JJH.

/, including a singlet at 30, (02H5)6SnOI)
, ? , -Oe? , % 0 (m, 'I H, o-
0106H,0),za,os(d.

JH, J=3.0Hz, / , 2, IA −
) riazolyl group-3 position), g,! ? 0-,? , ri0 (m, J H, / , J.

gutriazolyl group-3 position) ppm-"ONMB" (
ODOI, , TMS) δ: ? ;、? (5n
(OH2QH5)5)*/ 0.0 (5n(9H20
H5)s), /J/, 0, /Jto/.

L coj...? , / , 2 j, 7 , / J L
3, / J 1,6.

/ 3 /, 4C, / Ko 16. / 4 G, ji (
'0-CI06)I40).

/! 0. ／ 、 ／ ! ; 0. ! T,/!
; 3. za+ts','('+2, -triazolyl group) ppm- Example 6 1'1l (1'') (1' 11 (1') (IV') tri-n-zoterstannyl-7, co, lI-triazole [lI') (0, J s O'7 t, o,
q mmol) and o-chlorophenyldichlorophosphate [I'] (0, Og J Ta?, 0.0!At
n1. 0.33 mmol) was reacted with the same mK as in Example S in deuterated chloroform (o, 3smt;),
0-chlorophenylphosphorology 1, co, q-triacylyrttn'] and tri-n-butyltin chloride [N
′] was obtained.

'HNMR, (ODOI3. TMS) δ: o, t
o-J,,,? o (m.

5ttH, (o4shi)5Sn) +7. Oj 7.
'I O (product, gH.

0-01 (06H, o), g, o s (d,
, 2 H, J = 3. Ohz.

/, J, <4-triazolyl group-3 position), Za, ZaO-,
,90(m,,ZH,l,,Z,It-triazolyl group-8 position) ppnl・Example 7 (1') [11') (In') C~'] trimethylstannyl-l, , 2. g-)IJ77”-
(1') (0,/6.z,,?f,O,?mi!j mol) and p-chlorophenylphosphorodichlorite-r(1
') (0,0g39?,0.037m1,0..3.3
mmol) was reacted in deuterated chloroform (o, 3smt> as in example j to give p-chlorophenylphosphorology t, ONMR (ODOI, , TMS) δ: -o,
t ((OH5)5Sn)+i, zt, 6. i7+t,
s', t3o, ti, ia+2. y.

73 G, 0, / 4 < 6.3, / u 6
．． 6 (p-0HIj6H40).

Claims (1)

[Claims] An organophosphorochloridate compound represented by the general formula CI) and an imidazole represented by the general formula (If) or/or, 2. An organophosphoroimidazolyl compound or an organophosphoroimidazolyl compound represented by the general formula [■] characterized by reacting an organotin compound of It-triazole or organophosphoro-/, 2. II-Process for producing triazolido compound. (In the formula, R1 is an alkyl group or an aryl group, and n is 1
Or hail 2. ) aisnx (H) (wherein a2 is an alkyl group or an aryl group, and X is an imidazolyl group or t, x, It-t'). ) 1 (a o), -flpxn (m) (In the formula, JX and n have the same meanings as above.)